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Purpose: A fixed-dose combination (FDC) of proton pump inhibitors (PPIs) and antacid salts enables rapid acid suppression through the neutralizing effect of the antacid salt and the rapid absorption of PPIs. This study aimed to compare the pharmacokinetics (PKs) and pharmacodynamics (PDs) of a recently formulated FDC of esomeprazole and magnesium hydroxide to the enteric-coated esomeprazole in healthy subjects., Methods: A randomized, open-label, multiple-dose, two-treatment, two-way crossover design was conducted in healthy subjects. Forty-nine subjects were randomized to one of the two treatment sequences and received either the test drug (esomeprazole/magnesium hydroxide 40/350 mg) or reference drug (enteric-coated esomeprazole 40 mg) for 7 days in the first period and the alternative in the second period with a 14-day washout period. Blood samples were collected for up to 24 hours for PK assessment, and 24-hour gastric pH monitoring was conducted for PD assessment both before and after a single administration, as well as at a steady state after seven consecutive days of administration. The PK and PD parameters were compared between the two drugs., Findings: After multiple administrations, the median value of time to reach maximum concentration was faster in the test drug than in the reference drug, with a difference of 1.68 hours. The overall systemic exposure of the test drug was similar to that of the reference drug, and the PK parameter fell within the equivalence criteria. The test drug demonstrated a shorter time to reach gastric pH ≥ 4 compared to the reference drug (P = 0.0463). A decrease from baseline in integrated gastric acidity over 24 hours, which represents the degree of inhibition of gastric acid secretion, was equivalent between the two drugs., Implications: The fixed-dose combination of esomeprazole and magnesium hydroxide showed rapid absorption and quicker gastric acid suppression than enteric-coated esomeprazole with comparable PK and PD properties., Clinicaltrials: gov identifier: NCT04324905 (https://classic., Clinicaltrials: gov/ct2/show/NCT04324905)., Competing Interests: Declaration of competing interest Sung Hee Hong and Na Young Kim are full-time employees of Hanmi Pharmaceutical Co., Ltd., Seoul, Republic of Korea. The authors have indicated that they have no other conflicts of interest regarding the content of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Antacids are commonly used during pregnancy, and they are approved for the relief of symptoms of gastroesophageal reflux disease (GERD) during pregnancy. However, there are no reports of the quantification of the absorption of aluminum and magnesium in the antacid magaldrate in women. The aim of this study was to quantify the rate and magnitude of absorption of aluminum and magnesium in magaldrate., Methods: An open-label, controlled, randomized, one-treatment study with a two-group design was conducted in healthy women in a fed state. The volunteers had a standard breakfast, and 30 min later, they were given a single-medication sachet containing 500 mg of sodium alginate, 267 mg of sodium bicarbonate, 800 mg of magaldrate, and 120 mg of simethicone (group A, n = 8) or no medication (group B, n = 2). Blood samples were obtained 36 h before and up to 12 h after antacid administration. The method used for quantification was inductively coupled plasma-mass spectrometry., Results: There was no absorption of aluminum in any of the blood samples from the healthy volunteers who received the drug or in those from the control group. Magnesium was detected at normal concentrations., Conclusion: These findings suggest that the use of this antacid is safe and without risk in healthy women, including pregnant women., Clinical Trial Registration: Clinicaltrials.gov registration: NCT06367452., (© 2024. The Author(s).)

Objective: The 13 C-urea breath test (UBT) is the most widely used non-invasive diagnostic test for Helicobacter pylori. Debate continues to surround the possible interference of antacid intake on its result. This study aims to confirm the non-interference of almagate in the determination of H. pylori by UBT., Patients and Methods: Observational, multicentre study in adult patients treated with almagate in whom a UBT (TAUKIT®) was indicated. When the UBT result was negative, use of almagate was stopped for 30 days and the UBT was repeated. When the result was positive, no further determinations were made. The primary endpoint was the percentage of patients who, having had a negative result in the first breath test, were positive in the second after having stopped taking almagate (UBT false negatives, possibly attributable to almagate)., Results: Of the 167 evaluable patients, 59% were female, average age was 49 and 97% had gastrointestinal symptoms. The result of the first UBT was negative in 71% of cases. Of these, in the second UBT test after stopping the almagate, the negative result was confirmed in 97.5%. Out of the total number of cases evaluated, the rate of false negatives was 1.8%., Conclusions: Taking almagate has minimal or no interference in the result of UBT for the diagnosis of H. pylori infection. It can therefore be used in the weeks prior to a UBT., (Copyright © 2021 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Magnesium hydroxide (Mg(OH) 2 ), magnesium fluoride (MgF 2 ), and hydroxyapatite (HA) films on Mg are widely studied owing to their easy preparation and favorable corrosion protection. Nevertheless, the most suitable film with the best performance for biomedical applications between the three films remains unknown. Therefore, the performance of the three coatings from in vitro to in vivo must be systematically investigated. In this study, Mg(OH) 2 , MgF 2 , and HA films were fabricated on pure Mg. Electrochemical analysis and the hydrogen evolution test suggested that the HA film showed the best in vitro corrosion resistance, followed by MgF 2 and Mg(OH) 2 films. In vitro cell culture indicated that the extract of the MgF 2 -coated sample was most beneficial for the osteogenic differentiation of MC3T3-E1 cells and the vascularization of human umbilical vein endothelial cells (HUVECs), which might be ascribed to the existence of the F element in the film. The result of this subcutaneous implantation showed that the HA film exhibited the best in vivo corrosion resistance and induced the lightest inflammatory response. Femoral implantation data revealed that the HA film exhibited the best osseointegration. Furthermore, the major organs and blood indicators of all of the tested rats were normal in 8 weeks. In summary, though the in vitro biological performance of the MgF 2 film was the best among the three films, the HA film showed the best in vivo performance, suggesting that it is a more promising modification method for orthopedic applications.

Saxagliptin is an orally administered, highly potent, and selective dipeptidyl peptidase-4 inhibitor for the management of type 2 diabetes mellitus. This study was conducted to determine the effect of magnesium and aluminum hydroxides plus simethicone, famotidine, and omeprazole on the pharmacokinetics of saxagliptin and its active metabolite, 5-hydroxy saxagliptin. This was an open-label, randomized, 5-treatment, 5-period, 3-way crossover study in 15 healthy subjects. Mean C max of saxagliptin was 26% lower, but AUC was almost unchanged when saxagliptin was coadministered with Maalox Max. Mean C max was 14% higher, but AUC was almost unchanged when saxagliptin was coadministered with famotidine. Changes in pharmacokinetics of 5-hydroxy saxagliptin generally paralleled the changes in saxagliptin. These pharmacokinetic changes were unlikely to be clinically meaningful. Coadministration of omeprazole did not affect saxagliptin C max or AUC. Saxagliptin in combination with these medicines resulted in no unexpected safety or tolerability findings in these healthy subjects. No dose adjustment of saxagliptin or separation in the time of saxagliptin dosing is necessary with medicines that raise gastric pH when coadministered with saxagliptin., (© 2018, The American College of Clinical Pharmacology.)

Objective: Cardiac arrhythmias are a common challenge following open-heart surgeries. Hypomagnesemia is believed to be correlated with this condition. Prophylactic intravenous magnesium supplementation has been practiced for a long time in patients undergoing CABG. This study was designed in an attempt to compare the efficacy of oral versus intravenous routes in the prevention of hypomagnesemia and arrhythmia., Methods: In this interventional clinical study, 82 patients were randomly assigned to 2 groups. All patients were evaluated for baseline serum magnesium level and arrhythmias. One group received 1,600 mg of oral magnesium hydroxide through nasogastric (NG) tube prior to surgery, while the other group received 2 g of magnesium sulfate during the induction of anesthesia. The serum magnesium level was monitored for 48 hours after the operation. The difference in preoperative hypomagnesemia was non-significant (Sig: 0.576)., Results: During the operation, the serum magnesium level peaked around 4 mg/dL, and no hypomagnesemia was detected in any patient. Although the curve of oral group declined parallel and below that of intravenous (IV) group, no significant differences were detected during postoperative monitoring. In addition, a prevalence of arrhythmia of 13.9% and 6.5% was noticed in IV and oral groups, respectively (OR: 0.428)., Conclusion: Providing 1,600 mg of oral magnesium supplement to patients is as effective as 2,000 mg of magnesium sulfate IV in preventing hypomagnesemia and arrhythmia after CABG. Thus, the authors introduce this treatment regimen as a promising and cost-effective method.

Purpose: Beyond-use dating (BUD) of lidocaine alone and in two "magic mouthwash" preparations stored in amber oral syringes at room temperature was determined., Methods: Two formulations of mouthwash containing oral topical lidocaine 2% (viscous), diphenhydramine 2.5 mg/mL, and aluminum hydroxide-magnesium hydroxide-simethicone were prepared in 1:1:1 and 1:2.5:2.5 ratios, divided into 3-mL samples, and stored in unit-dose oral amber syringes. Unit-dose single-product lidocaine samples were also prepared to serve as controls and stored in oral amber syringes. The lidocaine concentrations in these samples were measured periodically for 90 days. A stability-indicating high-performance liquid chromatographic method was developed and validated for system suitability, accuracy, repeatability, intermediate precision, specificity, linearity, and robustness., Results: Based on the calculated percentages versus the initial concentration and the results from an analysis of variance comparing the two formulations, a BUD of 21 days is deemed appropriate for both magic mouthwash formulations. Based on the stability data, published safety concerns, and lack of efficacy in combination, packaging and dispensing lidocaine separately from other ingredients are recommended when administering magic mouthwash mixtures. Utilizing a 90-day BUD, lidocaine can be packaged separately from other magic mouthwash ingredients in individual dosage units and applied to the oral cavity using the swish-and-spit method. The delivery of the diphenhydramine and aluminum hydroxide-magnesium hydroxide-simethicone could be separated, allowing for a swish-and-swallow method of administration., Conclusion: A BUD of 21 days is recommended for lidocaine prepared with diphenhydramine and aluminum hydroxide-magnesium hydroxide-simethicone in ratios of 1:1:1 and 1:2.5:2.5 and stored at room temperature in amber oral plastic syringes., (Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Despite the presumption of a beneficial effect of magnesium (Mg) supplementation on various diseases, little is known concerning the pharmacokinetics of Mg hydroxide. This study was designed to provide a pharmacokinetic profile of Mg hydroxide after a single oral dose. Ten healthy male adults participated in this cross-over study with three 24-hr study days. Interventions were (i) none (baseline), (ii) oral intake of three (3 × 360 mg) tablets of Mg hydroxide (Mablet ® ) and (iii) IV bolus infusion of 2 g Mg sulphate (index drug). Blood samples were collected before the single dose, after (i.e. after treatment administration) 15, 30, 60, 90 and 120 min. and after 3, 4, 6, 8, 12 and 24 hr. Urine was collected in four 6-hr periods per study day. Blood (N = 10) and urine (N = 6) Mg were analysed by descriptive statistics. Bioavailability was 14.9% (CI: 8.3; 26.8), blood clearance was 5.1 L/hr (CI: 2.1; 17.0), apparent volume of distribution was 60.2 L (CI: 35.6; 102.0), elimination constant was 0.08 per hour (CI: 0.05; 0.14), half-life was 8.3 hr (CI: 4.8; 14.1), C max was 0.11 mmol/L (CI: 0.07; 0.14), and AUC [0-24] was 92.3 mmol/L × min. (CI: 45.5; 139.1). Urine Mg excretion augmented by 17.7% (CI: 8.9; 35.0) from baseline. No severe side effects were observed. The bioavailability of Mg hydroxide was 15%, and it constitutes a clinically relevant option for oral Mg supplementation. No severe side effects were seen., (© 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Aim: To evaluate the effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality., Methods: Forty-eight patients diagnosed with gastric ulcer between June 2014 and February 2016 were randomly allocated to the combination therapy group or monotherapy group. The former received hydrotalcite combined with esomeprazole, and the latter received esomeprazole alone, for 8 wk. Twenty-four healthy volunteers were recruited and acted as the healthy control group. Endoscopic ulcer healing was observed using white light endoscopy and narrow band imaging magnifying endoscopy. The composition of collagen fibers, amount of collagen deposition, expression of factor VIII and TGF-β1, and hydroxyproline content were analyzed by Masson staining, immunohistochemistry, immunofluorescent imaging and ELISA., Results: Following treatment, changes in the gastric microvascular network were statistically different between the combination therapy group and the monotherapy group ( P < 0.05). There were significant differences ( P < 0.05) in collagen deposition, expression level of Factor VIII and TGF-β1, and hydroxyproline content in the two treatment groups compared with the healthy control group. These parameters in the combination therapy group were significantly higher than in the monotherapy group ( P < 0.05). The ratio of collagen I to collagen III was statistically different among the three groups, and was significantly higher in the combination therapy group than in the monotherapy group ( P < 0.05)., Conclusion: Hydrotalcite combined with esomeprazole is superior to esomeprazole alone in improving gastric ulcer healing quality in terms of improving microvascular morphology, degree of structure maturity and function of regenerated mucosa., Competing Interests: Conflict-of-interest statement: The authors declared that there is no conflict of interest related to this study.

Objectives: Raltegravir is a human immunodeficiency virus (HIV)-1 integrase strand transfer inhibitor currently marketed at a dose of 400 mg twice daily (BID). Raltegravir for once-daily regimen (QD) at a dose of 1200 mg is under development. The effect of calcium carbonate and magnesium/aluminium hydroxide antacids on the pharmacokinetics of a 1200 mg dose of raltegravir was assessed in this study., Methods: An open-label, four-period, four-treatment, fixed-sequence study in 20 HIV-infected patients was performed. Patients needed to be on raltegravir as part of a stable treatment regimen for HIV, and upon entry into the trial received 5 days of 1200 mg raltegravir as pretreatment, before they entered the four-period study: 1200 mg of raltegravir alone (period 1), calcium carbonate antacid as TUMS ® Ultra Strength (US) 1000 and 1200 mg raltegravir given concomitantly (Period 2), magnesium/aluminium hydroxide antacid as 20 ml MAALOX ® Maximum Strength substitute MS given 12 h after administration of 1200 mg raltegravir (period 3), and calcium carbonate antacid as TUMS ® US 1000 given 12 h after administration of 1200 mg raltegravir (period 4). Patients received their dose of 1200 mg QD raltegravir during the intervals between periods to re-establish steady state. AUC 0-24 , C 24 , C max and T max were calculated from the individual plasma concentrations of 1200 mg QD raltegravir after administration alone or with a calcium carbonate antacid or with a staggered dose of a calcium carbonate antacid or magnesium/aluminium hydroxide antacid. Adverse events, in addition to laboratory safety tests (haematology, serum chemistry and urinalysis), 12-lead electrocardiograms and vital signs were assessed., Key Findings: All treatments were well tolerated in the study. Metal-cation antacids variably affected the pharmacokinetics of 1200 mg QD raltegravir. When calcium carbonate antacid was given with 1200 mg raltegravir concomitantly, the geometric mean ratio (GMR) and its associated 90% confidence interval (90% CI) for AUC 0-24 , C max and C 24 h were 0.28 (0.24, 0.32), 0.26 (0.21, 0.32) and 0.52 (0.45, 0.61), respectively. When calcium carbonate antacid and magnesium/aluminium hydroxide were given 12 h after raltegravir 1200 mg QD dosing, the GMR (90% CI) values for AUC 0-24 and C max were 0.90 (0.80, 1.03), 0.98 (0.81, 1.17), and 0.86 (0.73, 1.03), 0.86 (0.65, 1.15), respectively. However, significant reduction in the trough concentrations of raltegravir was observed: C 24 h 0.43 (0.36, 0.51) in the presence of calcium carbonate antacids and 0.42 (0.34, 0.52) in presence of magnesium/aluminium hydroxide, respectively., Conclusions: Overall, the use of metal-cation antacids with 1200 mg QD raltegravir is not recommended., (© 2016 Royal Pharmaceutical Society.)

Background/aims: Bile is the main cause of poor bowel preparation for capsule endoscopy (CE). We aimed to determine whether cholestyramine and hydrotalcite can eliminate bile in the bowel., Patients and Methods: Patients undergoing CE were randomized into two groups. Group A patients (n = 75) received 250 mL 20% mannitol and 1 L 0.9% saline orally at 20:00 hours on the day before and at 05:00 hours on the day of CE and 20 mL simethicone 30 min before CE. Group B patients (n = 73) were treated identically, except for taking oral cholestyramine and hydrotalcite, starting 3 days before CE. Greenish luminal contents were assessed by four tissue color bar segments using Color Area Statistics software. Bowel cleanliness was evaluated by visualized area percentage assessment of cleansing (AAC) score., Result: Bowel cleanliness (82.7% [62/75] vs 46.6% [34/73]; χ2 = 14.596, P = 0.000). and detected greenish luminal contents (20.0% [15/75] vs 8.2% [6/73]; χ2 = 4.217, P = 0.040) were significantly greater in Group A than in Group B. Greenish luminal contents in the two groups differed significantly in the captured small-bowel (t = -13.74, P = 0.000) segments and proximal small-bowel (t = -0.7365, P = 0.000) segments, but not for the distal small-bowel (t = -0.552, P = 0.581) segments., Conclusions: Cholestyramine and hydrotalcite were ineffective in eliminating bile and improving small-bowel preparation.

Background: Deflation cough (DC), i.e. the cough-like expiratory expulsive efforts evoked by maximal lung emptying, is partially inhibited by prior intake of an antacid. We wished to compare the effects of an anti-reflux medical device (Gastrotuss(®)) and of a widely used antacid drug (Maalox(®)) on the number of expiratory thrusts evoked by maximal lung emptying in chronic cough patients., Methods: Twenty consecutive chronic cough outpatients also presenting DC attended the clinic on three separate occasions and were requested to inhale to near total lung capacity and then exhale maximally for at least 6 s. Trained investigators detected aurally the number of cough efforts evoked by maximal lung emptying prior to and 1, 5, 10, 30 e 60 min after administration of either Maalox(®), or Gastrotuss(®) or placebo. The liking of the administered agents was also rated., Results: In control conditions, maximal lung emptying was consistently accompanied by the appearance of DC. The number of efforts was unchanged after placebo whereas it was markedly (P < 0.001) reduced 1-10 min following Maalox(®) and Gastrotuss(®) administration. The value of liking for Gastrotuss(®) was greater (P < 0.01) than those of Maalox(®) and placebo., Conclusions: Pre-treatment with anti-reflux agents with a substantially different composition are equally effective in inhibiting DC. The liking of the two compounds used in the present experiments differed considerably and may be important to improve adherence to treatment in patients undergoing long-term therapy for reflux-related symptoms., (Copyright © 2015. Published by Elsevier Ltd.)

Background/aims: Cholecystectomy is necessary for the treatment of symptomatic or complicated gallbladder (GB) stones, but oral litholysis with bile acids is an attractive alternative therapeutic option for asymptomatic or mildly symptomatic patients. This study was conducted to evaluate the efficacy of magnesium trihydrate of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on gallstone dissolution and to investigate improvements in gallstone-related symptoms., Methods: A prospective, multicenter, phase 4 clinical study to determine the efficacy of orally administered magnesium trihydrate of UDCA and CDCA was performed from January 2011 to June 2013. The inclusion criteria were GB stone diameter ≤15 mm, GB ejection fraction ≥50%, radiolucency on plain X-ray, and asymptomatic/mildly symptomatic patients. The patients were prescribed one capsule of magnesium trihydrate of UDCA and CDCA at breakfast and two capsules at bedtime for 6 months. The dissolution rate, response rate, and change in symptom score were evaluated., Results: A total of 237 subjects were enrolled, and 195 subjects completed the treatment. The dissolution rate was 45.1% and the response rate was 47.2% (92/195) after 6 months of administration of magnesium trihydrate of UDCA and CDCA. Only the stone diameter was significantly associated with the response rate. Both the symptom score and the number of patients with symptoms significantly decreased regardless of stone dissolution. Adverse events necessitating discontinuation of the drug, surgery, or endoscopic management occurred in 2.5% (6/237) of patients., Conclusions: Magnesium trihydrate of UDCA and CDCA is a well-tolerated bile acid that showed similar efficacy for gallstone dissolution and improvement of gallstone-related symptoms as that shown in previous studies.

During pregnancy, both the mother and fetus are vulnerable to environmental pollution by particulate matters and chemicals. Although the toxicity of free pollutants has been frequently reported, the impact of nanoparticle/pollutant adducts on the vulnerable pregnant population remains unclear. In this study, pregnant mice were orally exposed to Mg(OH)2 nanoflakes and nanoflakes adsorbed with Cr(VI) anions during the peri-implantation and organogenesis stages of pregnancy at doses that did not induce systemic toxicity or pregnancy complications. The nano-Mg(OH)2/Cr(VI) adducts formation reduced fetal developmental toxicity compared with the toxicity induced by the same concentration of free Cr(VI) anions., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Aim: To evaluate the effects of an Al(3+)- and Mg(2+)-containing antacid, ferrous sulfate, and calcium carbonate on the absorption of nemonoxacin in healthy humans., Methods: Two single-dose, open-label, randomized, crossover studies were conducted in 24 healthy male Chinese volunteers (12 per study). In Study 1, the subjects orally received nemonoxacin (500 mg) alone, or an antacid (containing 318 mg of Al(3+) and 496 mg of Mg(2+)) plus nemonoxacin administered 2 h before, concomitantly or 4 h after the antacid. In Study 2, the subjects orally received nemonoxacin (500 mg) alone, or nemonoxacin concomitantly with ferrous sulfate (containing 60 mg of Fe(2+)) or calcium carbonate (containing 600 mg of Ca(2+))., Results: Concomitant administration of nemonoxacin with the antacid significantly decreased the area under the concentration-time curve from time 0 to infinity (AUC0-∞) for nemonoxacin by 80.5%, the maximum concentration (Cmax) by 77.8%, and urine recovery (Ae) by 76.3%. Administration of nemonoxacin 4 h after the antacid decreased the AUC0-∞ for nemonoxacin by 58.0%, Cmax by 52.7%, and Ae by 57.7%. Administration of nemonoxacin 2 h before the antacid did not affect the absorption of nemonoxacin. Administration of nemonoxacin concomitantly with ferrous sulfate markedly decreased AUC0-∞ by 63.7%, Cmax by 57.0%, and Ae by 59.7%, while concomitant administration of nemonoxacin with calcium carbonate mildly decreased AUC0-∞ by 17.8%, Cmax by 14.3%, and Ae by 18.4%., Conclusion: Metal ions, Al(3+), Mg(2+), and Fe(2+) markedly decreased the absorption of nemonoxacin in healthy Chinese males, whereas Ca(2+) had much weaker effects. To avoid the effects of Al(3+) and Mg(2+)-containing drugs, nemonoxacin should be administered ≥2 h before them.

Objective: The aim of the present study was to evaluate the treatment adherence of children with chronic functional constipation., Methods: The present study is a prospective and longitudinal study realized at a pediatric gastroenterology clinic of a Brazilian University Hospital, between August 2009 and October 2011. Rome III criteria and the Bristol Stool Scale were used to define constipation and to characterize feces, respectively. Drug treatment was prescribed for patients according to the protocols previously standardized in the clinic. Specific questionnaires, containing questions related to 1 dependent variable and independent variables were completed in the first and sixth months of the treatment. Independent variables related to the patients, their caregivers, the disease itself, and the therapeutic plan were analyzed and compared with the dependent variable (adherence to the treatment). Adherence was considered when the patient returned with >75% of the prescribed medicine containers empty., Results: Fifty children participated in both the first and sixth months of treatment. The mean age of the sample was 77.6 ± 43.8 months and the mean age of the onset of symptoms was 18.8 ± 27.9 months. The adherence rate was 38% in the first month and 30% in the sixth month. Patients who were treated with polyethylene glycol had greater adherence than patients who were prescribed other laxatives, with statistical significance in the second moment of the study (P = 0.19 and P = 0.04, respectively)., Conclusions: The study showed low adherence rates to drug treatment of constipation in children. It is necessary to seek new strategies to increase treatment adherence, while avoiding complications and reducing costs.

This clinical case and the literature review show possible development of methemoglobinemia due to the use of local anesthetics, included in drugs for the gastrointestinal diseases treatment, in particular benzocaine, which is the methaemoglobin forming agent. These drugs are common and often taken by the patients themselves without any control. The aim of our paper is to draw the attention of physicians to the risk of the widely known drug administration which can be purchased without a prescription.

The aim of this work was to develop new mucoadhesive buccal patches containing an inorganic fluorinated compound, MgAl-F, intended for decay prevention. Firstly MgAl-F was synthesized and characterized, then the patches were prepared starting from a physical blend of mucoadhesive polymers (NaCMC and polycarbophil) in which MgAl-F was dispersed in different amounts in order to obtain the films. The prepared mucoadhesive patches were characterized in terms of swelling capacity, mucoadhesion force and time, surface morphology and in vitro release studies. Moreover, the organoleptic properties and acceptability have been evaluated by in vivo application. The performed studies demonstrated that the proposed formulations are practical, manageable, flexible and adaptable to the biological substrate showing, at the same time, good organoleptic properties. Moreover, the presence of the MgAl-F is able to decrease the strong adhesion of the employed polymers, reducing pain and irritations resulting in a high patient acceptability. Data obtained from release studies revealed that the application of small patch portions is enough able to release, for a prolonged time, an amount of fluoride ions able to reach the efficacious dose. These observations suggest the applicability of such formulations for buccal administration of different active ingredients., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Cisapride is a gastrointestinal prokinetic that facilitates or restores motility along the entire gastrointestinal tract. It has been used successfully to treat acute and chronic intestinal pseudo-obstructions (CIPs) in adults, but there is a paucity of literature surrounding the treatment of CIP in pediatric patients and therapies for CIP are limited and their impact is often unsatisfactory. This case report presents the use of cisapride in the management of pseudo-obstruction. Treatment with cisapride substantially improved the patient's symptoms and improved feeding tolerance. It improved his prognosis remarkably and prevented the need for end-of-life care. He experienced no adverse effects throughout the course of therapy. The treatment regimen is discussed in this case report.

Background: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a distinct subtype of non-Hodgkin lymphoma in which the upper aerodigestive tract is the most commonly involved site. To date, optimal treatment strategies and prognosis for patients with ENKTL have not been fully defined., Methods: This prospective study was conducted to evaluate the efficacy and safety profiles of first-line combined gemcitabine, oxaliplatin, and L-asparaginase (GELOX) followed by involved-field radiation therapy for patients with stage IE/IIE ENKTL. The primary endpoints were the complete response rate, the objective response rate, and toxicities. Secondary endpoints were overall survival and progression-free survival., Results: Twenty-seven patients with newly diagnosed ENKTL were enrolled and completed the entire course of treatment. At the end of treatment, the overall response rate was 96.3%, including 20 patients (74.1%) who attained a complete response and 6 patients (22.2%) who attained a partial response. No patients developed disease progression during therapy. Grade 1 and 2 toxicities were frequent during GELOX, but grade 3 and 4 toxicities were few, and no treatment-related deaths occurred. At a median follow-up of 27.37 months, 7 patients (25.9%) experienced disease progression, and 4 of those patients died of disease. The rates of 2-year overall and progression-free survival were both 86%, and patients who attained a complete response at the end of treatment had significantly longer progression-free survival (P = .012) and overall survival (P = .021) than patients who did not attain a complete response., Conclusions: The current results indicated that GELOX followed by involved-field radiation therapy can be an effective and feasible treatment strategy for patients with stage IE/IIE ENKTL of the upper aerodigestive tract. These results will require further investigation in larger prospective trials., (Copyright © 2012 American Cancer Society.)

Objective: Acid-related gastrointestinal symptoms are widely prevalent. These complaints are often self-medicated with antacids. For the community pharmacy setting little is known about how patients' perceptions of self-treating symptoms are met, e.g., via patient satisfaction. Such outcomes are difficult to determine in clinical trials, therefore, non-interventional studies (NIS) are one applicable method for gaining data under real-world conditions. This study was conducted to investigate: (1) characteristics of gastrointestinal symptoms and patients' global health status, (2) drug usage and symptom relief, and (3) patient satisfaction with the medication., Methods: This prospective, cross-sectional NIS was performed in cooperation with 137 community pharmacies in Germany. Participants were recruited from customers, after they had purchased the antacid, and were asked to complete a self-administered questionnaire. Patient satisfaction with hydrotalcite was assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM) on the scales effectiveness, side effects, convenience, and global satisfaction., Results: 548 patients answered the questionnaire. The following symptoms were reported most frequently: heartburn (65%) and acid regurgitation (37%). In comparison to the general population, more participants rated their global health in lower categories, e.g., satisfying (35% vs. 23%) or poor (12% vs. 5%). Drug usage patterns were found to be in accordance with the principles of self-medication. The majority of patients reported a noticeable symptom relief within 15 min after drug intake. TSQM mean scores were high in all four scales; an excellent score was achieved in the scale side effects. Study results also revealed that the self-perceived global health status of the patients had an impact on their global satisfaction with the medication., Conclusions: This NIS shows that patients (1) are often affected in their global health when suffering from acid-related symptoms, (2) observed a fast symptom relief after drug intake, and (3) are highly satisfied with the antacid hydrotalcite.

Context: Postoperative ileus is a major complication of abdominal surgical procedures, Objective: To evaluate the incidence of ileus and gastrointestinal morbidity in patients who received immediate postoperative feeding and bowel stimulation after undergoing major gynecologic surgical procedures., Methods: During a 5-year period, the authors tracked demographic, surgical outcome, and follow-up information for 707 patients who underwent major gynecologic operations. All patients received the same postoperative orders, including immediate feeding of a diet of choice and bowel stimulation with 30 mL of magnesium hydroxide (milk of magnesia) twice daily until bowel movements occurred., Results: Of 707 patients, 6 (<1%) had postoperative ileus. No patients experienced postoperative bowel obstruction and 2 patients (0.3%) had postoperative intestinal leak. No serious adverse effects associated with bowel stimulation were reported., Conclusion: Immediate postoperative feeding and bowel stimulation is a safe and effective approach to preventing ileus in patients who undergo major gynecologic surgical procedures.

Purpose: Systemic exposure to niflumic acid was significantly increased when talniflumate was given orally together with a meal. To clarify the underlying mechanism, an in vitro dissolution study of talniflumateonducted at different pH values, and magnesium hydroxide was co-administered in healthy volunteers., Methods: In vitro dissolution tests of talniflumate tablets were performed in a USP Paddle apparatus at pH 1.2, 4.0, and 6.8, respectively, in the presence and absence of Tween 80 (2%). Serial samples of the talniflumate solution were taken and analyzed on a high-performance liquid chromatography (HPLC)/ultraviolet system. Healthy volunteers were divided randomly into two groups, and each volunteer received a single 740-mg dose of talniflumate, with or without 1 g of magnesium hydroxide, following an overnight fast. The plasma concentrations of niflumic acid were measured using HPLC coupled with tandem mass spectrometry., Results: Talniflumate was completely insoluble at each of the tested pHs in the absence of Tween 80. The drug was slowly and steadily dissolved (54%) at pH 4 in the presence of the surfactant, but the extent of dissolution was only 15 and 0.5% at pH 1.2 and 6.0, respectively. Magnesium hydroxide co-administered with talniflumate significantly increased systemic exposure to niflumic acid: the mean maximum plasma concentration (C (max)) and area under the concentration-time curve (AUC (inf)) were augmented by 2.0- and 1.9-fold, respectively, compared with those in the absence of the antacid. Magnesium hydroxide significantly accelerated the appearance of niflumic acid in plasma by 2.8-fold., Conclusions: Magnesium hydroxide increases the rate and extent of systemic exposure to niflumic acid owing to the enhanced solubility of talniflumate and absorption of niflumic acid. The possible combination of talniflumate and an antacid should be considered in the development of pharmaceutical formulations.

Objective: To compare the effectiveness of two drugs, polyethylene glycol 4000 without electrolytes and magnesium hydroxide, in the treatment of chronic functional constipation in children., Methods: Thirty-eight children were randomly assigned to either of two groups, polyethylene glycol 4000 without electrolytes or magnesium hydroxide. The children were followed through periodic appointments until they reached 6 months of treatment. In each medical appointment the following aspects were evaluated: stool consistency, frequency of bowel movements, fecal incontinence, abdominal pain, straining and acceptance of the drugs., Results: Seventeen children made use of polyethylene glycol and twenty-one received magnesium hydroxide. All variables analyzed improved for both groups, with no statistically significant differences. All children accepted polyethylene glycol, while 42.9% refused magnesium hydroxide., Conclusion: The two laxatives showed no difference in effectiveness for the treatment of constipation. However, due to its better acceptance, because it is odorless and tasteless, polyethylene glycol proved to be a better option for treating chronic functional constipation.

Background: Routine laxatives may expedite gastrointestinal recovery and early tolerance of food within an enhanced recovery after surgery (ERAS) programme. Combined with carbohydrate loading and oral nutritional supplements (ONS), it may further enhance recovery of gastrointestinal function and promote earlier overall recovery., Methods: Seventy-four patients undergoing liver resection were randomized in a two-by-two factorial design to receive either postoperative magnesium hydroxide as a laxative, preoperative carbohydrate loading and postoperative ONS, their combination or a control group. Patients were managed within an ERAS programme of care. The primary outcome measure was time to first passage of stool. Secondary outcome measures were gastric emptying, postoperative oral calorie intake, time to functional recovery and length of hospital stay., Results: Sixty-eight patients completed the trial. The laxative group had a significantly reduced time to passage of stool: median (interquartile range) 4 (3-5) versus 5 (4-6) days (P = 0.034). The ONS group showed a trend towards a shorter time to passage of stool (P = 0.076) but there was no evidence of interaction in patients randomized to the combination regimen. Median length of hospital stay was 6 (4-7) days. There were no differences in secondary outcomes between groups., Conclusion: Within an ERAS protocol for patients undergoing liver resection, routine postoperative laxatives result in an earlier first passage of stool but the overall rate of recovery is unaltered., (Copyright (c) 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Lersivirine (UK-453,061) is a next-generation nonnucleoside reverse transcriptase inhibitor that displays potent antiviral activity. Lersivirine solubility is pH dependent; therefore, the effect of coadministration of antacid on the pharmacokinetics of lersivirine in healthy subjects was investigated. The ratio of adjusted geometric means (750 mg lersivirine plus 20 ml Maalox Max/750 mg lersivirine alone) for the area under the curve from time zero extrapolated to infinite time (AUC(inf)) was 101.86%, showing that coadministration of an antacid had no effect on lersivirine exposure. Coadministration appeared to be safe and relatively well tolerated.

Background/aims: This study was designed to compare the efficacy and patient tolerance between standard bowel preparation using 4 liters of polyethylene glycol (PEG) solution and 4 liters of PEG preceded by the osmotic laxative, magnesium hydroxide in constipation and non-constipation group., Methods: 173 outpatient colonoscopy, except for three patients who were not taking magnesium, were divided into constipation and non-constipation group. Then, the patients were randomly assigned to receive 4-liter of PEG solution or 4-liter of PEG plus magnesium hydroxide. The quality of bowel preparation was assessed using Ottawa scale, and satisfaction score was assessed using questionnaires. Solid stool, cecal intubation time, compliance, and side effects were assessed., Results: Non-constipation group showed no significant differences between two groups. In constipation group, 4-liter PEG solution plus magnesium hydroxide induced the more effective colonic preparation (Ottawa scale 2.47+/-0.99 vs. 5.92+/-2.39, p<0.05), and less solid stool (0.67+/-0.72 vs. 1.38+/-0.65, p<0.05) compared with 4-liter PEG solution., Conclusions: Bowel preparation with magnesium hydroxide and 4 liters of PEG solution might reduce solid stool in constipation group, but could not improve preparation quality.

Background: Regardless of surgical technique, patients who have undergone cholecystectomy appear to be predisposed to the development of bile reflux gastritis., Objective: To assess the efficacy of rabeprazole and hydrotalcite in patients with bile reflux gastritis after cholecystectomy., Methods: Postcholecystectomy patients with bile reflux gastritis confirmed by endoscopy and 24 h gastric bilirubin monitoring were randomly assigned to one of four eight-week treatments: observation (group A), rabeprazole alone (group B), hydrotalcite alone (group C) and rabeprazole in combination with hydrotalcite (group D). Endoscopy and 24 h gastric bilirubin monitoring were repeated in all patients after treatment. Dyspeptic symptoms of abdominal pain, bloating, heartburn, bitter taste, endoscopic and histological finding, and biliary reflux were evaluated before and after treatment., Results: After administering medication, patient symptoms in groups B, C and D were relieved - most significantly in group D (P<0.05). There were no significant differences in endoscopic hyperemia and histological inflammation among the groups (P>0.05). However, histological activity, the number of reflux episodes and the number of reflux episodes lasting longer than 5 min were significantly decreased only in group D (P<0.05). The total per cent of bilirubin absorption (value of 0.14 units or greater) time was decreased in groups B, C and D, and most significantly in group D (P<0.05)., Conclusion: Rabeprazole combined with hydrotalcite is an effective therapeutic option in the treatment of patients with bile reflux gastritis after cholecystectomy.

Excessive ingestion of magnesium may lead to hypermagnesemia even without kidney dysfunction. Several cases of development of hypermagnesemia after overdose of magnesium hydroxide have been reported. Although magnesium hydroxide is widely used as laxative, its overdose may induce diarrhea, which is followed by excessive magnesium loss. I report a case of paradoxical hypomagnesemia developed after excessive ingestion of magnesium hydroxide. A 39-year-old woman was presented to the emergency department complaining of severe watery diarrhea and carpopedal spasm after ingesting a handful of magnesium hydroxide tablets. The laboratory tests detected hypomagnesemia, hypocalcemia, and normokalemia. Calcium gluconate was given to the patient, but her symptom did not improve shortly. The symptom disappeared spontaneously 2 days after the watery diarrhea subsided. This case shows that overdose of magnesium hydroxide, which leads to massive diarrhea, might induce hypomagnesemia unexpectedly. This case also suggests that it should be treated, as well as typical magnesium deficiency.

Objectives: To evaluate the effect of the anthroposophic drug hepar magnesium D10 intravenously administered on seasonal fatigue symptoms., Design: Time series with two measurements per week, starting before onset of treatment until three measurements after finishing treatment in a regular way., Settings: Six anthroposophic general practitioner practices in the Netherlands., Subjects: Twenty-three (23) patients with seasonal fatigue symptoms., Interventions: Hepar magnesium D10 intravenously administered every week., Outcome Measures: Mean division of 24 hours in categories: sleep, rest, everyday activities, and activities that require a large effort; fatigue-related single questions: unusual emotional response to events, problems with short-term memory, the degree to which fatigue after effort continues for longer than 2 hours, the degree to which people at the end of the day have a complete lack of energy; and the degree to which people are still fit after the evening meal; Multidimensional Fatigue Index: general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue; subjective experiences with regard to the effect of the treatment., Results: (1) No changes in division in 24-hour categories were found; (2) pretreatment versus post-treatment analyses (after 1 and 2.5 weeks, at the end of treatment, and 1.5 weeks after the end of treatment) demonstrated overall large statistically significant differences. Eighteen (18) of 22 patients (82%) who completed the final questionnaire judged that treatment overall had been effective for their fatigue symptoms. Nine (9) patients (41%) judged a strong improvement and 9 patients (41%) a light improvement as a result of the treatment. Four (4) patients reported no change. On average, patients received treatment 4.5 times., Conclusions: There are clear indications that hepar magnesium D10 intravenously administered can have a positive effect on subsyndromal seasonal affective disorder symptoms of fatigue. A more controlled trial is indicated to study the (long-term) effects of hepar magnesium.

Objective: Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor used for the treatment of dyslipidaemia, may be co-administered with antacids in clinical practice. This trial assessed the effect of simultaneous and separated administration of an antacid preparation containing aluminium hydroxide 220 mg/5 mL and magnesium hydroxide 195 mg/5 mL (co-magaldrox 195/220) on the pharmacokinetics of rosuvastatin., Research Design and Methods: A randomised, open-label, three-way crossover trial was performed. Healthy male volunteers (n = 14) received a single dose of rosuvastatin 40 mg alone, rosuvastatin 40 mg plus 20 mL antacid suspension taken simultaneously, and rosuvastatin 40 mg plus 20 mL antacid suspension taken 2 h after rosuvastatin on three separate occasions with a washout of > or = 7 days between each., Main Outcome Measures: The primary parameters were area under the rosuvastatin plasma concentration-time curve from time zero to the last quantifiable concentration (AUC(0-t)) and maximum observed rosuvastatin plasma concentration (C(max)) in the absence and presence of antacid., Results: When rosuvastatin and antacid were given simultaneously, the antacid reduced the rosuvastatin AUC(0-t) by 54% (90% confidence interval [CI] for the treatment 0.40-0.53) and C(max) by 50% (90% CI 0.41-0.60). When the antacid was given 2 h after rosuvastatin, the antacid reduced the rosuvastatin AUC(0-t) by 22% (90% CI 0.68-0.90) and the C(max) by 16% (90% CI 0.70-1.01). The effect of repeated antacid administration was not studied and it cannot be discounted that this may have resulted in a stronger interaction than that observed here., Conclusions: Simultaneous dosing with rosuvastatin and antacid resulted in a decrease in rosuvastatin systemic exposure of approximately 50%. This effect was mitigated when antacid was administered 2 h after rosuvastatin.

A 77-year-old man was admitted to our hospital due to macrohematuria and bladder tamponade. Bladder hemorrhage caused by radiation therapy had not improved after bladder lavage, intravesical drip infusion, medication of hemostatics, and transurethral coagulation. Bladder hemorrhage had completely disappeared 7 days after the intravesical instillation of 50-100 ml aluminium hydroxide gel and magnesium hydroxide for an hour per day. This method is easy and can be performed without complications. This method might be useful as first-line therapy in the case of severe bladder hemorrhage.

The potential interaction of the H2-receptor antagonist famotidine (CAS 76824-35-6) with calcium carbonate (CAS 471-34-1) and magnesium hydroxide (CAS 1309-42-8) during administration of the famotidine fixed dose combination (FDC) formulation was investigated. A randomized, open-label, two-period, crossover study was carried out on 12 healthy Chinese volunteers. Plasma concentration-time profiles of famotidine were similar with the FDC formulation and common formulation. Confidence interval (90% CI) for maximal concentration (C(max)) and area under the curve (AUC(o-t)) of famoti-dine were 94.8-112.2% and 94.2-112.3%, respectively. These findings suggest that calcium carbonate/magnesium hydroxide antacids have no significant effects on famotidine pharmacokinetics when they are administered together with famotidine as an FDC formulation.

Background: Postoperative atrial fibrillation has been refractory to many attempted pharmacologic prevention methods and, when effective, side effects have been described. The present aim was to study the clinical compliance of a suggested prophylactic treatment, oral sotalol, and magnesium., Methods: Coronary-bypass patients without clinical contraindications to receive oral sotalol (80 mg twice daily) and magnesium supplementation were enrolled (n = 49) with an intention-to-treat strategy and being compared with a matched control group (n = 844). A protocol listed exclusion criteria of clinical compliance that was postoperatively evaluated prior to and during treatment., Results: Twenty-seven of the 49 enrolled patients (55%) were compliant to sustain the treatment according to the protocol. The remaining patients were postoperatively excluded, mainly because of hemodynamic reasons, of whom 14 were noncompliant to initiate any treatment. The AF occurrence in the compliant group was 7% versus 36% in noncompliant patients (p = 0.035), and 24% in the control group (p = 0.076). However, with an intention-to-treat policy the overall AF incidence became 18%. The subgroups of enrolled patients demonstrated skewing phenomena. The noncompliant group had higher requirement for inotropic support (p = 0.029) and longer aortic cross-clamp time (p = 0.048) compared to compliant patients. Further, the body weight of noncompliant patients was markedly lower than in the compliant counterpart (p = 0.015)., Conclusions: The tested treatment protocol showed limited compliance among routine cardiac-surgery patients, and further, introduced a biased selection of patients that skewed the results and may have partly explained the treatment effect.

Study Objective: To evaluate the effect of an aluminum- and magnesium-containing antacid (Al-Mg antacid), which contains a high concentration of cations, on the pharmacokinetics of garenoxacin., Design: Prospective, randomized, open-label, control-balanced, residual-effects-design study., Setting: Pharmaceutical company-affiliated study clinic., Subjects: Twenty healthy volunteers who were garenoxacin naïve., Intervention: Subjects were randomly assigned to receive three of six oral treatments, each separated by a 7-day washout period: garenoxacin 600 mg administered alone, with concomitant Al-Mg antacid, 2 or 4 hours before Al-Mg antacid, or 2 or 4 hours after Al-Mg antacid. The Al-Mg antacid dose was 20 ml, which contained aluminum hydroxide 900 mg and magnesium hydroxide 800 mg., Measurements and Main Results: The pharmacokinetics and safety of garenoxacin were assessed. For each treatment, serial blood samples for pharmacokinetic analysis of garenoxacin were collected before and up to 72 hours after garenoxacin dosing. Absence of effect of Al-Mg antacid on garenoxacin area under the concentration-time curve from time zero extrapolated to infinity (AUC(0-infinity)) and maximum observed plasma concentration (C(max)) were concluded if the 90% confidence interval of the adjusted geometric mean ratios with and without the antacid were contained within 0.80-1.25 and 0.70-1.43, respectively. Exposure to garenoxacin measured by AUC(0-infinity), a parameter well correlated with efficacy, was reduced by 58% when coadministered with Al-Mg antacid and reduced by 22% and 16% when administered 2 and 4 hours after the antacid, respectively. Administration of garenoxacin 4 hours before Al-Mg antacid had no effect on AUC(0-infinity) or C(max) of garenoxacin, whereas administration 2 hours before the antacid resulted in a nonclinically relevant (12%) reduction in AUC(0-infinity) of garenoxacin., Conclusion: Exposure to garenoxacin was significantly decreased when garenoxacin was coadministered with Al-Mg antacid or within 2 hours after the antacid. The magnitude of the changes in garenoxacin exposure suggests that garenoxacin should be administered at least 2 hours before or 4 hours after administration of Al-Mg antacid or other cation-containing products.

Non-prescribed antacid drugs that contain magnesium and aluminum are widely used in the treatment of gastritis and peptic ulcer. One of the side effects of these antacid drugs is that they bind phosphate in the gut and result in its malabsorption. In this paper, a 42-year-old female patient who used magnesium hydroxide (Magnesie calcinee powder 100 g) to benefit from its laxative feature, and developed osteomalacia after losing 90 kg in 2 years will be presented by going through the related literature. She had widespread joint pain and could hardly walk without the help. Ca, P and vitamin D were at lower limit of normal, ALP, Mg and PTH were increased in her laboratory tests. There were stress fractures at the femur neck and at the upper part of the tibia in plane radiographies. The patient was hospitalized with the diagnosis of osteomalacia and she was treated successfully.

In some multidrug therapy programs, ketoconazole (KTZ) may be administered with some antacids that could modify its dissolution rate and reduce its absorption, thus leading to therapeutic failures. The primary aim of this study was to evaluate the influence of Compritol HD5 ATO and Compritol 888 ATO on this interaction in comparison with commercial KTZ tablets. The second aim was to prepare lipid granules of KTZ that could be an alternative to the commercial formulation. Therefore, six KTZ sustained-release granules were prepared with different lipid concentrations, because they were found to be more suitable than tablets that are dissolved only in gastric medium. The results confirmed that the dissolution rate of KTZ granules was significantly reduced in the presence of antacids. The ideal formulation was selected as granules including 5% of Compritol lipids in relation to the suitability of the target profile. Therapeutic effects of orally administered, ideal KTZ granule formulations, and commercial tablets were evaluated in vivo by the experimental model of murine vulvo-vaginal candidiasis (VVC) with and without antacids. It was found that formulations were very effective on VVC, and the therapeutic effect decreased significantly in the presence of antacids. Histopathological studies were carried out for vagina, stomach, and liver tissues and hepatoxicity was also examined. The levels of reduced glutathione (GSH) were measured to assess the oxidative stress induced by KTZ and function of the liver. It was observed that orally administered formulations of KTZ were successful in treating candidiasis in mice without irritancy in stomach. However, liver tissues were damaged. The decreased GSH levels indicated toxicity in our study. This study suggested that in vitro release and in vivo microbiological-toxicological properties of KTZ were affected by antacids and drug-excipient interactions. Lipid granules of KTZ prepared with Compritol 888 ATO could be proposed as a new KTZ solid dosage form with optimum dissolution and therapeutic characteristics.

Background: Rennie and Riopan Gel are 2 of the most well-known and popular over-the-counter antacids; for heartburn symptoms, pain relief is fast with both preparations. A direct comparison with respect to intragastric acidity has not been done yet. The aim of our study was therefore to compare the effects of both preparations on intragastric acidity of fasting volunteers., Methods: The study was conducted as an open, randomised, placebo-controlled, 2-centre cross-over study. On different days, 24 healthy adult volunteers (11 males and 13 females) received equimolar acid-neutralising amounts of either Riopan Gel (800 mg magaldrate) or 2 tablets of Rennie (680 mg calcium carbonate and 80 mg magnesium carbonate) or no drug (control) with a wash-out period of at least 4 days between applications. The intragastric pH was measured for 3 h by intragastric pH-metry. The primary endpoint was the median time lag before intragastric pH >3.0 was reached for 10 consecutive min after drug administration., Results: For both antacids, the median pH during the first 30 min after drug administration was statistically significantly different from placebo (p < 0.05), but there was a statistically significant increase in pH during the first 5 min for Riopan Gel only., Conclusion: Compared to placebo, both antacids (Rennie and Riopan Gel) have short-lasting effects on intragastric acidity. There is no statistically significant difference between the 2 preparations, except in the first 5 min, indicating a faster onset of action for Riopan Gel. We conclude that the antacid formulation (tablet or liquid) has little influence on intragastric acidity., (2007 S. Karger AG, Basel)

Objective: New quinolones (NQs) are widely used to treat various infections. However, concomitant oral administration of metal cations may decrease absorption of NQs and consequently decrease their blood concentration and pharmacological effect. A convenient approach to avoid this interaction is to separate the dosages by a certain interval. In this study, we aimed to develop a novel pharmacokinetic model to describe NQs-metal cation interactions in order to estimate the optimal dosing interval., Methods: Plasma concentration-time profiles of NQs after administration without or with metal cations at various dosing intervals were collected from the literature and analyzed with a pharmacokinetic model incorporating the formation ofNQs-metal cations complex. The model was fitted to the reported time profiles ofciprofloxacin (CPFX) plasma concentration after concomitant administration with aluminum hydroxide/magnesium hydroxide antacid (Al/Mg antacid; Maalox, Maalox70) at various dosing intervals to obtain the pharmacokinetic parameters of CPFX. Model analysis was also carried out for gatifloxacin (GFLX) and norfloxacin (NFLX)., Results: The developed model could adequately explain the interactions in all the combinations investigated. The model predicted, in the cases of usual doses of CPFX with Maalox, GFLX with Maalox70 and NFLX with sucralfate, that the NQ should be administered 4.5, 4.5 and 3.5 hours after, or 1, 1 and 0.5 hours before the administration of metal cations, respectively, to ensure 90% of control absorption., Conclusions: The developed model can adequately describe the extent of interaction between NQs and metal cations, and should be clinically useful to design dosage regimens to circumvent the interaction.

We have established and documented an in vivo bioassay for detection of hazards with intratracheally instilled fine particles, which can be used for risk assessment of toxicity of materials inhaled into deep lung tissue of humans (Yokohira et al. Establishment of a bioassay system for detection of lung toxicity due to fine particle instillation: sequential histopathological changes with acute and subacute lung damage due to intratracheal instillation of quartz in F344 male rats. J Toxicol Pathol 2005;18:13-8). For validation we here examined toxicity of fine particles from quartz, hydrotalcite, potassium octatitanate, palladium oxide and carbon black with this bioassay. A total of 108, 10-week-old F344/DuCrj male rats were randomly divided into 8 groups. Groups 1 to 5 underwent intratracheal instillation of the 5 test particles (4 mg/rat) suspended in 0.2 ml vehicle (saline or 10% propylene glycol and 1% sodium carboxymethyl cellulose in saline: PG-CMC) with a specially designed aerolizer, and subgroups of 7 rats were killed on Days 1 and 28 thereafter. Groups 6 and 7 similarly were exposed to saline and PG-CMC, respectively, as vehicle controls, while group 8 was maintained untreated. Using histopathological changes and immunohistochemically assessed bromodeoxyuridine (BrdU) labeling indices, inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-3 (MMP-3) levels as end points, the quartz treated group exhibited high toxicity, while the values for the other particle-treated groups pointed to only slight effects. Although additional efforts are needed to establish advantages and disadvantages with our bioassay, models featuring intratracheal instillation clearly can be useful for detection of acute or subacute lung toxicity due to inhaled fine particles by using histopathological scoring and markers like BrdU and iNOS for screening purposes in short-term studies.

The aims of the present study were to compare effects of sodium alginate and the antacid magaldrate anhydrous in adults with gastroesophageal reflux (GOR) symptoms. Patients with heartburn and/or acid regurgitation for at least 3 days in the week before the study started (n=203) were randomized to receive a single dose of sodium alginate or magaldrate anhydrous at the onset of symptoms during a 3-day run-in period. Patients with symptoms during the run-in (n=191) were rerandomized to receive a 14-day treatment with either drug given as four daily doses. A speed of action < or =30 min was significantly more frequent among patients in the alginate group (49.4% vs. 40.4%; P=0.0074). A trend toward a more prolonged duration of action (median: 16.5 vs. 12.7 hr) and a greater sum of the symptom intensity difference (median: 40.0 vs. 31.0) was observed in the sodium alginate group. Total disappearance of symptoms was reported in 81.6% and 73.9% of patients in the sodium alginate group and magaldrate group, respectively. We conclude that sodium alginate was faster than magaldrate in relieving GRO symptoms and showed a tendency toward a more prolonged duration of action and a higher level of efficacy.

Purpose: The objectives of this study were (1) to describe the usage of topical oral solutions in patients experiencing chemotherapy-induced oral mucositis (CIOM); and (2) to survey the care of oral mucositis provided to patients by clinical oncology pharmacists in institutional settings., Methods: Surveys were distributed to institutional pharmacists in the US, who were asked to provide the components of their 'magic mouthwash'. Other questions included whether an institutional mucositis management guideline is available and what is the involvement of clinical pharmacy in mucositis care., Results: Forty institutions returned surveys during the study period. The top five ingredients used to compound the magic mouthwash are diphenhydramine, viscous lidocaine, magnesium hydroxide/aluminum hydroxide, nystatin and corticosteroids. Most institutions administer the mouthwash every 4 hours (36%) or every 6 hours (36%). Of the surveyed institutions, 33% currently possess guidelines for the management of CIOM., Conclusions: Most institutions in the country formulate their topical solution, or magic mouthwash, with a variety of ingredients. There is a need to standardize the ingredients used to compound the magic mouthwash, in order to fully evaluate the efficacy of the solution to manage CIOM.

Hydrotalcite is a biocompatible lamellar anionic clay formed by double hydroxide layers with a metal cation coordinating four OH groups. The different layers are held together by anionic hosts that can be replaced by a simple ion-exchange process. The synthetic Mg-Al-hydrotalcite was used to intercalate ferulic acid, a compound that shows antioxidant properties due to its free radical scavenger capacity. Analysis of the intercalated compound showed a good intercalation percentage (35.53%) accompanied by an increase of the interlayer space from 7.8A (chloride form) to 17.1A due to the presence of the ferulate. The intercalation product was stable in water, did not show any significant degradation after UV-irradiation, had a higher capacity of UV absorption in comparison to both the pure ferulic acid and ferulic acid-hydrotalcite chloride physical mixture. The intercalated compound was formulated in a siliconic cream and the ferulate in vitro release profiles determined.

Single doses of MAALOX TC and ranitidine were administered separately with 1,400 mg of fosamprenavir (FPV). MAALOX TC decreased the area under the concentration-time curve from 0 to 24 h (AUC(0-24)) for plasma amprenavir (APV) by 18% and the maximum concentration of drug in serum (C(max)) by 35%; the plasma APV concentration at 12 h (C(12)) increased by 14%. Ranitidine at 300 mg decreased the AUC(0-24) for plasma APV by 30% and C(max) by 51%; C(12) was unchanged. FPV may be coadministered with antacids without concern and without separation in dosing; however, caution is recommended when FPV is coadministered with histamine(2)- receptor antagonists or proton pump inhibitors.

We hypothesized that Benzocaine (Hurricaine) would work as quickly and effectively as viscous Lidocaine in this preparation. This was a prospective randomized, single-blinded comparison between Benzocaine and Lidocaine as the topical anesthetic in a gastrointestinal (GI) cocktail. Patients 18 years or older were approached for participation when a GI cocktail was ordered by the Emergency Physician. Patients were randomized to equivalent doses of either Benzocaine or viscous Lidocaine in addition to 30 cc of Maalox and 10 cc of Donnatal. Assessment using a visual analog pain scale occurred at time intervals of 0, 5, 15, and 30 min. Eighty-two patients were enrolled (44 to Benzocaine, 38 to viscous Lidocaine), with each group having a statistically significant improvement in pain (p < 0.001). There were no statistical differences between the Benzocaine and viscous Lidocaine groups in terms of the relief of symptoms at each of the assessment times. There were no adverse outcomes in either group.

This study was conducted to determine the effects of oral magnesium hydroxide administration on rumen fluid in cattle. Six lactating Holstein cows (4-7 years of age) with rumen fistulas were studied. Cattle were randomly assigned to receive boluses of magnesium hydroxide (162 g) or a powdered form (450 g dissolved in 3.5 L of water) PO daily for 3 days. Analysis of rumen fluid, blood gas tensions, and pH and measurement of serum magnesium concentrations were conducted daily. The study was discontinued after 72 hours, or sooner if rumen pH exceeded 8.0. After at least 3 weeks, the study was repeated with each cow receiving the other form of magnesium hydroxide (powder or bolus). Compared with baseline rumen pH (mean +/- SD: 6.22 +/- 0.28), magnesium hydroxide boluses caused a significant increase (P < .05) in rumen pH after 48 (7.27 +/- 0.11) and 72 (8.01 +/- 0.16) hours of administration, whereas the powdered form caused a significant increase (P < .05) in rumen pH after 24 (7.54 +/- 0.19) and 48 (8.43 +/- 0.22) hours of administration. Both the powdered and bolus forms of magnesium hydroxide decreased rumen protozoal numbers and increased methylene blue reduction times compared with baseline values. There was no change in blood pH, bicarbonate, or base excess values. Serum magnesium concentrations were significantly increased (P < .05) in cows that received the magnesium hydroxide powder. The results of this study indicate that magnesium hydroxide has a potent alkalinizing effect on rumen pH and significantly decreases rumen microbial activity.

Objectives: To compare the safety and efficacy of pantoprazole with ranitidine for the maintenance of endoscopically documented healed (grade 0 or 1) erosive oesophagitis., Methods: Patients (371) were randomly assigned to receive pantoprazole 10, 20 or 40 mg or ranitidine 150 mg. Endoscopies were performed after 1, 3, 6 and 12 months or when symptoms suggesting relapse (grade = 2) developed. Gastric biopsies were obtained at baseline and on at least one postbaseline visit. Symptom-free days and Gelusil use were assessed., Results: Pantoprazole was significantly (P < 0.001) more effective in maintaining erosive oesophagitis healing. After 12 months, 33%, 40%, 68% and 82% of patients remained healed for the ranitidine and pantoprazole 10, 20 and 40 mg groups, respectively. Daytime and night-time heartburn were eliminated in > 90% of days for the pantoprazole 40 mg group. Gelusil use was significantly lower with pantoprazole 20 and 40 mg than with ranitidine (P < 0.02) during the first 9 months., Conclusions: Twelve months of maintenance therapy with pantoprazole (10-40 mg once daily) was superior to ranitidine (150 mg twice daily) in maintaining erosive oesophagitis healing. Pantoprazole 40 mg provided the most consistent efficacy and was well tolerated.