Search

Due to the differences between bioavailability of efavirenz (EFV) and tenofovir (TDF), the single-tablet regimen of EFV/emtricitabine (FTC)/TDF is not approved as initial antiretroviral therapy (ART) in Europe by the European Medical Agency. To compare clinical, immunological, and virological outcomes between co-formulated TDF/FTC+EFV and the co-formulated EFV/FTC/TDF single-tablet regimen in patients infected with HIV-1 naive to ART, the data of patients (n = 231) who initiated either TDF/FTC+EFV (n = 155) or EFV/FTC/TDF (n = 76) between January 1, 2007 and June 1, 2010 were analyzed. Changes from baseline to week 48 (TDF/FTC+EFV vs. EFV/FTC/TDF) in HIV plasma load (- 3.25 log vs. -3.32 log) and CD4+ T cell count (+180 vs. +138 cells/mm3) were similar in the two groups. Treatment discontinuation was recorded in 50 (22%) patients (40 on TDF/FTC+EFV and 10 on EFV/FTC/TDF, P = 0.03) but time to discontinuation did not differ between the two groups. Only patients on TDF/FTC+EFV discontinued treatment because of neurological symptoms. Virological failure occurred in 11 (4.7%) patients (seven on TDF/FTC+EFV and four on EFV/FTC/TDF, P = 0.75) with new resistance-associated mutations in five among the six with successful resistance genotype tests. Only baseline resistance-associated mutations was a risk factor for virological failure (P = 0.0146). These data show comparable outcomes between TDF/FTC+EFV or EFV/FTC/TDF used in patients infected with HIV-1 and not treated previously, consistent with a low rate of virological failure in the absence of pretreatment resistance. This would suggest that the European Medical Agency should approve co-formulated EFV/FTC/TDF single-tablet regimen for patients naive to ART., (© 2014 Wiley Periodicals, Inc.)

Recently, we reported a number of key, common medications that affect the air passages in a variety of fashions. The purpose of this article is to provide a comprehensive review of the literature on the subject, including supportive articles published in languages other than English. The presented information was gathered by a review of the English literature, by cross referencing, and by communication with other interventional pulmonologists. We identified several additional medications causing either direct or systemic effects on the air passages. In this review, we update the clinical presentation, mechanism of injury, diagnosis, and management of the airway complications related to these medications.

Aims: AFN-1252 is a novel inhibitor of FabI, an essential enzyme in Staphylococcus spp. This study was undertaken to assess the safety, tolerability and pharmacokinetic properties of AFN-1252, following oral administration in an ascending dose trial., Materials & Methods: This was a double-blind, randomized, placebo-controlled, two-part study. In Part I, single doses (QD) of 100, 200, 300, or 400 mg AFN-1252 were administered. In Part II, subjects received 200, 400, 600, or 800 mg (total daily dose) where 100, 200 and 400-mg doses were given twice in one day., Results: AFN-1252 was well-absorbed with Cmax at 3-4 h when given once per day and 2.5-9 h when dosed twice in a single dosing day. T½ ranged from 8 to 11 h. Total and peak exposures of AFN-1252 increased nonlinearly. Adverse events were primarily mild and resolved promptly., Conclusions: Oral doses of AFN-1252 were safe and well tolerated. AFN-1252 has the potential for once or twice-a-day dosing for treatment of staphylococcal infections.

Background: The safety and efficacy of pre- and coseasonal sublingual allergen immunotherapy (SLIT) with a 5-grass pollen sublingual tablet have been demonstrated in a randomized clinical trial (RCT) in children and adolescents. Observational, 'real-life' studies can usefully complement the results of RCTs., Methods: A prospective, open-label, observational, multicentre post-marketing study of children and adolescents (aged 5-17, with grass pollen-induced allergic rhinitis) treated with the 5-grass pollen sublingual tablet was performed between June 2009 and January 2011 in Germany. Adverse events (AEs) were recorded during consultations with the investigating physicians; AEs judged to have at least a possible causal link to the tablet were classified as adverse drug reactions (ADRs)., Results: Eight hundred and forty-nine patients were enrolled (by 207 investigating physicians), 829 (mean ± s.d. age: 10.9 ± 3.3 yr) completed the study without major protocol deviations, and 796 were fully documented with respect to AEs. Ninety-four of the 796 patients (11.8%) experienced at least one ADR on the first day of SLIT and 218 (27.4%) experienced at least one ADR during the study. Four hundred and sixty-six of the 596 ADRs (78.2%) were mild or moderate. The most common ADRs were throat irritation (19.1% of the reactions), oral paresthesia (8.2%), oral pruritus (6.5%) and oedema mouth (6.2%). Serious ADRs occurred in five patients. No epinephrine use was reported. Seventy-six of the 829 patients (9.2%) discontinued SLIT due to AEs. Tolerability was judged to be good or very good by patients (84.7%), parents (87.0%) and investigators (89.7%)., Conclusions: In clinical practice, pre- and coseasonal treatment with a 5-grass pollen sublingual tablet is safe and well tolerated in children and adolescents., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Subcutaneous allergen-specific immunotherapy has long been used in the treatment of allergic rhinitis and/or asthma and its efficacy has been confirmed. However, due to the discomfort of injections and the risk of severe adverse reactions, alternative routes of allergen administration have emerged. Delivery of allergens through the mucosal route had been proposed and investigated thoroughly, confirming the sublingual route to be the most efficacious. Later, the efficacy and safety of this route have been documented by numerous controlled trials both for house dust mite (HDM) and pollens. Recently, sublingual orodispersable grass pollen allergen tablets were in use followed by the newly developed HDM allergen tablets with satisfactory clinical results: Moreover, very recently 1 year of HDM tablet treatment was demonstrated to exert its clinical efficacy 1 year after discontinuation of tablet IT. The persistence of efficacy after only 1 year of treatment is a new and promising era. Currently, Sublingual Immunotherapy is the most easily administered and safe treatment option until more immunogenic, less allergenic and more efficient allergen extracts are developed.

Objective: To investigate the nephrotoxic effects of methyl cantharidimide tablets on urinary protein and enzymes in Beagle dogs., Method: Beagle dogs were randomly divided into negative control group(blank tablet), methyl cantharidimide tablets group (6.11,12.21, 24.42 mg x kg(-1)), continuously 30 days of oral adminiStration, once a day. The drug and control group were collected and determined fresh urine in 1, 2, 3 and 4 weeks of the administration; Serum urea nitrogen (BUN), creatinine (Crea), total protein (TP) and albumin (ALB) as well as sodium, potassium, chloride electrolyte were determined on 15 and 30 days of the administration; Urine albumin (mAlb), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin( NGAL), N-acetyl-beta-D-glucosaminidase (NAG), clusterin, beta2-microglobulin (beta2-MG), alpha1-microglobulin (alpha1-MG), alanine aminopeptidase( AAP) and im- munoglobulins IgG were tested on 15 and 30 days of the administration., Result: Compared with the control group, urine protein and white blood cells was significantly increased in each dose group. On 15 days of the administration, mAlb were higher in each dose group, KIM-1, NGAL, clusterin, NAG and AAP were significantly higher in high-dose group, while the middle and low dose group had no significant difference, as well as blood SCr and BUN no obvious abnormalities. On 30 days, mAlb, KIM-1, clusterin, NAG, AAP were increased in each dose group, appearing dose-effect relationship, beta2-MG and NGAL levels were significantly increased in high-dose group. Contents above indicators were increased with significant dose and time relationship, and serum BUN, Scr were correlated, suggesting that urine mAlb, KIM-1, clusterin, NAG and AAP indicators that can sensitively respond the changes of proteins and enzymes in urine., Conclusion: Methyl cantharidimide tablets has a renal toxicity, urine mAlb, KIM-1, clusterin, NAG and AAP can be used as the early nephrotoxic biomarkers of methyl cantharidimide tablets.

We evaluated posaconazole serum concentrations and hepatotoxicity in 12 leukemia patients who transitioned from posaconazole suspension to tablets. Patients who switched to tablets had significantly increased posaconazole concentrations (median: suspension, 748 ng/ml; tablet, 1,910 ng/ml; P < 0.01) without clinically relevant hepatotoxicity., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Medication injury in the gastrointestinal tract (GIT) is a rapidly evolving topic. Increasing endoscopy together with an ageing population, polypharmacy, and a burgeoning drug industry offer heightened opportunities to observe the unintended side effects of therapeutic ingestants. In this review, we emphasise the most commonly encountered medication injuries involving the GIT, as well as emerging agents and mimics. While topics are organised by organ system, the reader should keep in mind that injury patterns are generally not site-specific. As such, awareness of these major morphologic patterns can be translated to multiple tissue sites to more broadly facilitate the diagnostic process.

Foreign body aspiration in adults without any background risk factors is uncommon. We report a 64 year gentleman evaluated for persistent cough incidentally detected to have a foreign body (FB) in the left main bronchus (LMB), which after removal by rigid bronchoscopy turned out to be a tablet. This demonstrates the possible risk of silent aspiration of solid foreign bodies and in our case presenting as a persistent cough after months of aspiration. Bronchoscopic evaluation should be carried out in the differential diagnosis of persistent or recurrent pulmonary symptoms.

Posaconazole tablets, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those with acute myelogenous leukemia or myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea, vomiting, or chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablets and to identify the dose of posaconazole tablets that would provide exposure within a predefined range of exposures (steady-state average concentration [area under the concentration-time curve/24 h] of ≥500 ng/ml and ≤2,500 ng/ml in >90% of patients). The study evaluated two sequential dosing cohorts: 200 mg posaconazole once daily (n = 20) and 300 mg posaconazole once daily (n = 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for ≤28 days. The exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200 mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg posaconazole once daily; 300 mg posaconazole once daily achieved the desired exposure target. Posaconazole tablets were generally well tolerated in high-risk neutropenic patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01777763.)., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Background: Investigations meeting current standards are limited for the effect of house dust mite (HDM) allergy immunotherapy in asthmatic patients., Objective: This trial investigated the efficacy and safety of a standardized quality (SQ; allergen standardization method proprietary to the trial sponsor) HDM SLIT-tablet (ALK, Hørsholm, Denmark) in adults and adolescents with HDM respiratory allergic disease. This publication reports the results of the endpoints related to asthma., Methods: Six hundred four subjects 14 years or older with HDM allergic rhinitis and mild-to-moderate asthma were randomized 1:1:1:1 to double-blind daily treatment with one of 3 active doses (1, 3, or 6 SQ-HDM) or placebo. Their use of inhaled corticosteroid (ICS) was standardized and adjusted at baseline and the end of treatment to the lowest dose providing asthma control. The primary end point was a reduction in ICS dose from the individual subject's baseline dose after 1 year of treatment., Results: The primary analysis revealed a mean difference between 6 SQ-HDM and placebo in the reduction in daily ICS dose of 81 μg (P = .004). Relative mean and median reductions were 42% and 50% for 6 SQ-HDM and 15% and 25% for placebo, respectively. No statistically significant differences were observed for the other assessed asthma parameters, reflecting the intended controlled status of the trial subjects. The most common adverse events were local reactions in the mouth. The rate and severity of adverse events were higher for 3 and 6 SQ-HDM than for 1 SQ-HDM and placebo., Conclusion: Efficacy in mild-to-moderate asthma of 6 SQ-HDM relative to placebo was demonstrated by a moderate statistically significant reduction in the ICS dose required to maintain asthma control. All active doses were well tolerated., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: To compare steady-state (ss) pharmacokinetic targets of nevirapine extended-release (NVP-XR) tablets once-daily (QD) with immediate-release (NVP-IR) tablet or oral suspension twice-daily in HIV-1-infected children and adolescents., Methods: Phase I, open-label, multidose, cross-over study with optional extension phase, in 85 patients 3 to <18 years of age, previously on an NVP-IR-based regimen for ≥18 weeks with baseline viral load <50 copies/mL. Patients were stratified by age, treated with NVP-IR twice-daily for 11 days, then NVP-XR QD for 10 days. Cpre,ss (steady-state, predose concentrations) was obtained from all, and 12-hour NVP-IR and 24-hour NVP-XR steady-state pharmacokinetic profiles were obtained in the pharmacokinetic substudy. Viral loads, CD4 counts and adverse events (AEs) were monitored., Results: Eighty patients completed the trial. Adjusted geometric mean (gMean) Cpre,ss for NVP-XR and NVP-IR exceeded the target of 3000 ng/mL, and the adjusted gMean NVP-XR:NVP-IR ratio (90% confidence interval) for QD normalized and un-normalized Cpre,ss were 91.2% (83.5-99.6%) and 91.8% (83.7-100.7%). gMean 24-hour area under the curve at steady-state NVP-XR:NVP-IR for un-normalized dose was 90.4% and un-normalized Cpre,ss NVP-XR:NVP-IR were 91.0%, 81.9% and 103.7% for the 3 age groups, 3 to <6, 6 to <12 and 12 to <18 years, respectively. gMean values indicated no exposure to subtherapeutic NVP concentrations and viral suppression was adequate and maintained in all QD groups. Most AEs were mild and similar between age groups. No serious or Division of AIDS Grade 4 AEs or AE related treatment discontinuations occurred., Conclusions: NVP-XR exhibited adequate trough concentrations with equivalent area under the curve at steady-state relative to NVP-IR. NVP-XR was well-tolerated and is a valuable treatment option for HIV-infected children and adolescents.

Tracheobronchial foreign body aspiration is a major cause of morbidity and mortality. The incidence of foreign body aspiration decreases significantly with increasing age, resulting in atypical presentations in adults. A high index of suspicion is required in adults presenting with respiratory symptoms. We present a rare case of a foreign body (pill) aspiration in an elderly female mimicking an obstructing endobronchial lesion.

Introduction: Acute toxic ingestion is a common cause of morbidity and mortality. Emergency physicians (EP) caring for overdose (OD) patients are often required to make critical decisions with incomplete information. Point of care ultrasound (POCUS) may have a role in assisting EPs manage OD patients. We evaluated the impact of different liquid adjuncts used for gastric decontamination on examiners' ability to identify the presence of tablets using POCUS, and assessed examiners' ability to quantify the numbers of tablets in a simulated massive OD., Methods: This prospective, blinded, pilot study was performed at an academic emergency department. Study participants were volunteer resident and staff EPs trained in POCUS. Five nontransparent, sealed bags were prepared with the following contents: 1 liter (L) of water, 1 L of water with 50 regular aspirin (ASA) tablets, 1 L of water with 50 enteric-coated aspirin tablets (ECA), 1 L of polyethylene glycol (PEG) with 50 ECA, and 1 L of activated charcoal (AC) with 50 ECA. After performing POCUS on each of the bags using a 10-5 MHz linear array transducer, participants completed a standardized questionnaire composed of the following questions: (1) Were pills present? YES/NO; (2) If tablets were identified, estimate the number (1-10, 11-25, >25). We used a single test on proportions using the binomial distribution to determine if the number of EPs who identified tablets differed from 50% chance. For those tablets identified in the different solutions, another test on proportions was used to determine whether the type of solution made a difference. Since 3 options were available, we used a probability of 33.3%., Results: Thirty-seven EPs completed the study. All (37/37) EP's correctly identified the absence of tablets in the bag containing only water, and the presence of ECA in the bags containing water and PEG. For Part 2 of the study, most participants - 25/37 (67.5%) using water, 23/37 (62.1%) using PEG, and all 37 (100%) using AC - underestimated the number of ECA pills in solution by at least 50%., Conclusion: There may be a potential role for POCUS in the evaluation of patients suspected of acute, massive ingested OD. EPs accurately identified the presence of ECA in water and PEG, but underestimated the number of tablets in all tested solutions.

Background: Sildenafil citrate is indicated for the treatment of erectile dysfunction. An orally disintegrating tablet (ODT) of sildenafil citrate has been developed for the benefit of patients who have difficulty swallowing solid dosage forms., Objective: The main goal of this study was to evaluate the bioequivalence of sildenafil ODT with and without water versus marketed sildenafil oral film-coated tablets. A secondary objective was to evaluate the effects of a high-fat meal on the pharmacokinetics of sildenafil ODT., Methods: The bioequivalence study of sildenafil ODT given with and without water versus marketed sildenafil citrate film-coated oral tablets was conducted in 36 subjects. In a food-effect study, the effect of a standard high-fat meal on the pharmacokinetics of sildenafil ODT was evaluated in 12 subjects. Both studies were randomized, open-label, crossover, single-dose (50 mg) studies in healthy men aged ≥45 years. Plasma samples were collected for 14 hours postdose, and pharmacokinetics were determined by using noncompartmental analyses., Results: All subjects in both studies were Asian males between the ages of 45 and 69 years. Sildenafil ODT without water was bioequivalent to the marketed sildenafil film-coated oral tablet as the 90% CI for the ratio of geometric means of Cmax, AUC0-∞, and AUC0-last were contained within equivalence limits (80%-125%). When sildenafil ODTs were given with water, the 90% CIs for sildenafil AUC0-∞ and AUC0-last were contained within the range of 80% to 125%; however, the 90% CI for sildenafil Cmax was not (79.76-92.78). This difference in Cmax is unlikely to have any clinically meaningful impact. High-fat meals reduced the rate but not the extent of absorption of sildenafil. Mean Cmax was reduced by 59%, and median Tmax was delayed from 0.625 hour (fasting) to 4 hours (high-fat meal). However, AUC values were comparable between fed and fasted treatments., Conclusions: Sildenafil ODT, given with or without water, provides equivalent systemic exposure compared with marketed sildenafil film-coated oral tablets, thus offering a convenient alternative method of administration. Considering the results of the food-effect study, sildenafil ODT should be taken on an empty stomach. ClinicalTrials.gov identifiers: NCT01254383 (bioequivalence) and NCT01254396 (food effect)., (Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.)

Background: The solubility of valsartan is dependent on pH and thus may cause patient variability in drug absorption and failure in bioequivalence studies; thus, increasing the solubility and release of valsartan at low pH has been suggested for a more favorable pharmacokinetic profile. However, due to this pH dependence, the change in the formulation process could alter the disintegration and/or dissolution profile of the drug, possibly making the results of bioequivalence studies misleading., Objective: The aim of this study was to assess the bioavailability and tolerability of a newly developed oral formulation of valsartan 160 mg (wet-granulation tablet) in healthy Korean male volunteers., Method: This study was performed with the subjects under fasted conditions, using a randomized, single-dose, 2-period crossover design. Subjects were assigned to receive, in randomized order, a single dose of the test formulation and a reference formulation (valsartan 160-mg dry-granulation tablet), with a washout period of 7 days between the administrations. Blood samples were collected up to 24 hours after dosing, and pharmacokinetic parameters were determined after the plasma valsartan concentration was analyzed using UPLC-MS/MS. The dissolution studies of both formulations were conducted using USP apparatus 2 at 50 rpm with 1000 mL of phosphate buffer solution (pH, 6.8) at 37°C ± 0.5°C. Bioequivalence was defined per Korean Food and Drug Administration's regulatory criteria as 90% CIs of the geometric mean test/reference ratios of AUC0-t and Cmax within the range of 0.8 to 1.25. Tolerability was assessed using physical examination and subject interviews., Results: Sixty subjects were enrolled (mean [SD] age [range], 23.6 [2.4] years [21-31]; height, 173.7 [6.6] cm [161-190]; and weight, 68.0 [8.7] kg [54-85]). The mean AUC0-∞ values with the test and reference tablets were 31,784 (13,844) and 32,714 (14,512) ng · h/mL, respectively; Cmax, 5094 (2061) and 5064 (1864) ng/mL; Tmax, 2.92 (1.04) and 3.08 (1.01) hours. The 90% CIs for the geometric mean test/reference ratios of AUC0-t and Cmax were 0.9295 to 1.0546 and 0.9190 to 1.0848, respectively, which met the criteria for bioequivalence. The most frequently reported adverse event was dizziness after blank blood sampling, recorded in 4 subjects, 2 cases each with the test and reference formulations., Conclusions: In this study in healthy Korean male volunteers, the test and reference formulations of 160-mg valsartan met the Korean Food and Drug Administration's regulatory criteria for bioequivalence despite the difference in formulation (wet granulation vs dry granulation). Both formulations were well tolerated, with no serious adverse events reported., (Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.)

The quad pill is the newest single-pill, once-daily option for the treatment of human immunodeficiency virus (HIV) type 1 infection. In addition to tenofovir difumarate (TDF) and emtricitabine (FTC), the quad pill includes cobicistat (COBI; an inactivator of cytochrome P450 isoenzyme CYP3A without anti-HIV activity) and a new integrase inhibitor, elvitegravir (EVG). The quad does not have drug interactions with H2-receptor antagonists or proton pump inhibitors, does not cause central nervous system (CNS) side effects, and is pregnancy category B. It does have substantial drug interactions with medications that are metabolized using CYP3A and causes reversible declines in estimated glomerular filtration rate (eGFR) owing to inhibition of renal tubule transport of creatinine. In clinical trials, the virologic and immunologic efficacy of the quad pill is equivalent to that of other comparator regimens with low rates of discontinuation. The major side effect is nauseam which is self-limited, and the primary mutations associated with treatment failure frequently lead to cross-resistance with raltegravir (RAL).

Both researchers and practitioners have reached an influential period in the new era of developing pediatric medicines. Evolving regulatory reforms and guidance continue to serve as platforms steering research and development while distinctive opportunities and challenges in the field emerge. An advancing research need involves gaining a better understanding of end-user requirements and acceptability of formulations. This review considers solid oral forms to demonstrate the importance of such research to stakeholders in policy and practice.

Objective: To assess the effect of concomitant food intake on the relative bioavailability of ospemifene and its main metabolite, 4-hydroxyospemifene, after single oral dosing., Methods: This was an open-label, randomized, balanced, two-treatment (fed vs. fasted), two-period, two-sequence cross-over study in 24 healthy male subjects. Single 60-mg doses of ospemifene were administered without food or with a high-fat, high-energy breakfast (860 kcal). In an extension study, a single 60-mg dose of ospemifene was given to 12 subjects with a low-fat, light breakfast (300 kcal). Additional information was acquired by determining tablet dissolution profiles in media which reflected fasted and fed intestinal conditions., Results: The AUC0-72 h and Cmax of ospemifene were 2.8- and 3.6-fold higher after a high-fat breakfast and 1.9- and 2.3-fold higher after a low-fat breakfast when compared with an overnight fast. The variability in both primary pharmacokinetic parameters was considerably reduced (by up to 50%) with a meal, indicating more consistent absorption of ospemifene with concomitant food intake. Dissolution in conditions simulating fed intestinal fluid (high bile acid concentration) was increased 3-fold compared with dissolution in simulated fasted intestinal fluid., Conclusions: wood markedly enhanced the extent and predictability of ospemifene absorption. The increase in bioavailability was not linearly related with the fat content of the meal. In vitro dissolution results were consistent with these clinical observations. Administration with food enhances and standardizes the oral bioavailability of ospemifene. Thus, it is recommended that ospemifene tablets should be taken with food.

Aspiration of a medication in the airways in any form produces a variety of adverse effects, both local and systemic. Furthermore, specific reaction of the airways to each type of pill strongly affects the outcome. It is crucial for pulmonologists and emergency medicine specialists to acknowledge this clinical entity. In addition, airways have been increasingly used to deliver medications such as insulin and prostacycline. These aerosolized medications can also cause local as well as systemic side effects. We review the local and systemic reactions of these "pills" accessing the airways either by incidental aspiration or iatrogenic administration. We address clinical presentation, mechanism of injury, diagnosis, and management of complications of these pills in the air passages.

Background: This study evaluated treatment satisfaction, gastrointestinal tolerability, depressive symptoms and alterations in laboratory parameters before and after switching from ritonavir capsule to tablet formulation., Methods: HIV+ adults switching from ritonavir capsules to tablets were eligible for the study. The HIV Treatment Satisfaction Questionnaire (HIVTSQ), Gastrointestinal Symptom Rating Scale (GSRS) and CES-D Depression inventory were self-administered before, and 3-4 months after switching. Results of laboratory tests within three months of each questionnaire were collected. A subset underwent plasma drug level sampling. Wilcoxon signed rank sum test was used for comparison of continuous variables and McNemar's test for dichotomised data., Results: Most of the 71 participants were Caucasian men, median age 51 years. Participants were taking ritonavir in combination with either atazanavir (n=48 [67.6%]), darunavir (n=18 [25.4%]), fosamprenavir (n=3 [4.2%]) or saquinavir (n=2 [2.8%]). In general after the switch to tablets, participants reported improved treatment satisfaction (median [interquartile range] HIVTSQ score 53/60 [48, 58] after vs 49/60 [45, 54] before, p <0.001), fewer gastrointestinal symptoms (GSRS score 4/45 [1, 9] vs 5/45 [3,13], p < 0.001) and had higher HDL cholesterol (1.22 mmol/L [1.07, 1.45] vs 1.09 mmol/L [0.90,1.32], p = 0.003) and lower total cholesterol/HDL ratio (3.82 [3.05, 4.40] vs 4.23 [3.45, 4.84], p<0.001). There were no significant changes in plasma viral load, CD4 counts, depression scores, or atazanavir or ritonavir trough levels., Conclusion: Results of this study suggest that the newer tablet formulation of ritonavir is better tolerated and has fewer gastrointestinal side effects than the older capsule formulation.

Medication in patients undergoing enteral intubation addresses various challenging issues considering safety and treatment efficiency. Ideally, other routes of administration (i.e. intravenous or intramuscular routes) or especially dedicated formulations should be used. However, in absence of liquid dosage form, tablets or pills must be crushed and suspended in a vehicle before administration. The administration of oral dosage forms by enteral tube is usually performed by the nursing staff facing (i) pharmaceutical relevance of crushing, (ii) loss and concomitant aero-contamination of drug substance, (iii) drug-nutriment interactions and (iv) enteral feeding tube clogging. In the present study, different combinations of either open or confined crushing and suspending protocols were compared by taking into account the crushing yield, the stability and granulometry of the solid oral form suspension and finally the extend of aerosol contamination during crushing and suspending. All protocols exhibited comparable crushing efficiency and suspending properties, but significantly higher aerosolisation of tablet particles was observed in both open crushing and suspending protocol. Therefore, both confined crushing and suspending protocol constitutes an efficient, time saving and safe alternative to the absence of available liquid dosage form for intubated patients., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Doxylamine succinate, an ethanolamine-based antihistamine, is used in the short-term management of insomnia because of its sedative effects. The data available on the pharmacokinetic profile of doxylamine in humans are limited, notwithstanding that this drug has been marketed in European countries for more than 50 years. In fact, no data on the effect of food on the pharmacokinetic parameters of doxylamine are available., Objective: The objective of this study was to evaluate the pharmacokinetic parameters of doxylamine following a single oral dose of doxylamine hydrogen succinate 25 mg in healthy human subjects under fed and fasting conditions., Study Design: This was a single-center, randomized, single-dose, laboratory-blinded, two-period, two-sequence, crossover study., Setting: The study was conducted in a phase I clinical unit., Subjects and Methods: A single oral dose of doxylamine hydrogen succinate 25 mg (equivalent to 17.4 mg of doxylamine base) was administered to healthy volunteers under either fed conditions (high-fat, high-calorie food intake) or fasting conditions in each study period. The drug administrations were separated by a wash-out period of seven calendar days. Plasma samples were collected for up to 60 hours postdose, and plasma doxylamine concentrations were determined by a high-performance liquid chromatography method with tandem mass spectrometry detection. Pharmacokinetic parameters were calculated using noncompartmental analysis. Safety was evaluated through assessment of adverse events, standard laboratory evaluations, vital signs, and 12-lead electrocardiography., Results: In total, 24 healthy subjects (12 male and 12 female) were included in the study. Doxylamine succinate 25 mg tablets exhibited similar oral bioavailability of doxylamine in the fasting state (mean maximum plasma drug concentration [C(max)] 118.21 ng/mL, coefficient of variation [CV] 19.2%; mean area under the plasma concentration time curve from time zero to time t [AUC(t)] 1746.97 ng · h/mL, CV 31.6%) and in the fed state (mean C(max) 120.99 ng/mL, CV 15.0%; mean AUC(t) 1712.20 ng · h/mL, CV 26.7%). No statistically significant between-treatment differences were observed for any of the pharmacokinetic parameters under study. The fed : fasting ratios of the geometric least squares means with corresponding 90% confidence intervals for C(max) and AUC(t) were within the range of 80-125%., Conclusion: High-fat, high-calorie food intake does not affect the kinetics of doxylamine in healthy subjects. The drug was safe and well tolerated by the subjects in this study.

Objectives: Posaconazole is an extended-spectrum triazole with proven efficacy as antifungal treatment and prophylaxis. The marketed oral suspension should be taken with food to maximize systemic absorption. A new solid oral tablet has been developed with improved bioavailability that can be administered without regard to food. The aim of this study was to evaluate rising single- and multiple-dose pharmacokinetics, safety and tolerability of the new tablet., Methods: This was a single-centre, randomized, placebo-controlled, Phase I, rising single- and multiple-dose study of healthy subjects aged 18-65 years who received a posaconazole tablet as 200 mg once daily, 200 mg twice daily or 400 mg once daily. The 24 subjects were studied in two cohorts of 12 subjects each (9 active and 3 placebo)., Results: After single or multiple oral dose administration of posaconazole tablets (200 and 400 mg), exposure increased in a dose-related manner. Peak posaconazole concentrations were attained at a median T(max) of 4-5 h. Mean half-life was similar for 200 and 400 mg posaconazole doses (25 and 26 h). The accumulation ratio upon multiple doses over 8 days was ∼3 for 200 and 400 mg once daily and ∼5 for 200 mg twice daily. C(avg) values exceeded 1300 ng/mL. The posaconazole oral tablet was safe and well tolerated, although mild, transient elevations in liver function were reported in some patients., Conclusions: Posaconazole exposure increased in a dose-related manner. The pharmacokinetics of this new solid oral tablet of posaconazole supports the clinical evaluation of once-daily dosing regimens for fungal infections.

Galenic science is interested in the art and the way of formulating an active principle with an excipient in order for it to be administered to the patient. The pharmaceutical forms envisage different administration routes, including by mouth. Nurses need to handle and sometimes modify the pharmaceutical form of a drug to make it easier for the patient to take. This requires vigilance.

What Is Known and Objectives: Ropinirole hydrochloride, a dopamine receptor agonist with a non-ergot alkaloid structure, is highly selective for the dopamine D(2) /D(3) receptors. This study was conducted to evaluate the steady-state pharmacokinetics, safety and efficacy after repeated oral administration of prolonged-release tablets of ropinirole hydrochloride in the absence of L-dopa preparations in Japanese patients with Parkinson's disease (PD)., Methods: This was a multicenter, open-label, uncontrolled study. The total duration of participation in the study ranged from 56 to 63 weeks. In the study, the plasma concentrations of ropinirole, its major metabolite SK&F104557 (N-depropyl ropinirole) and another metabolite SK&F89124 (ropinirole hydroxylated at the seventh position of the indole ring) were assessed. Safety based on adverse events, haematology, biochemistry, urinalysis and electrocardiography (ECG) (standard 12-lead ECG) were evaluated, and vital signs (blood pressure/pulse rate) were measured. Efficacy based on the Japanese version of Unified Parkinson's Disease Rating Scale (UPDRS) Parts III (motor) and II [activities of daily living (ADL)] as well as tolerability was evaluated., Results: After repeated oral administration of prolonged-release tablets of ropinirole hydrochloride in Japanese patients with PD, ropinirole, SK&F104557 and low levels of SK&F89124 were detected in plasma. The trough concentrations of ropinirole and the two metabolites increased in proportion to the dose when ropinirole hydrochloride prolonged-release tablets were administered at doses ranging from 2 to 16 mg/day. The plasma exposure to ropinirole and its two metabolites after intake of normal diet was comparable to that in the fasting state. The most common adverse events (10% or more) were somnolence, nausea, constipation, hallucination and nasopharyngitis. Most adverse events were mild or moderate in severity, and with no death. During the treatment period, serious adverse events were reported in five patients. Efficacy analysis (LOCF) at the final endpoint up to week 16 demonstrated a mean (SD) change from baseline in the Japanese UPDRS III (motor) and II (ADL) scores of -11·3 (8·21) and -3·9 (3·22), respectively, and thereafter remained at similar levels until week 52., What Is New and Conclusions: After administration of prolonged-release tablets of ropinirole hydrochloride in the absence of L-dopa preparations in Japanese patients with PD, the plasma pharmacokinetics of ropinirole and its metabolites was linear and not affected by food. Compared with the immediate-release (IR) tablet, the prolonged-release tablet can be administered to Japanese patients with PD at a reduced daily dose frequency and adjusted to the maintenance dose after fewer dose changes with a smaller diurnal variation in the plasma ropinirole concentration., (© 2012 Blackwell Publishing Ltd.)

Atenolol is a selective β1 receptor antagonist that is available as a racemic mixture. The objective of this study was to compare the pharmacokinetics and evaluate the bioequivalence of 50 mg atenolol test and reference formulations in 24 healthy Korean male volunteers.This study was a single-dose, randomized, open-label, 2 period crossover study. 24 healthy Korean male volunteers randomly received 50 mg of either test or reference atenolol formulations in a 2×2 crossover study. There was a 1 week washout period between doses. The area under the curve (AUC)0-24 h and Cmax of 50 mg atenolol were the primary criteria for evaluation of bioequivalence.The mean ± standard deviation (SD) values of the Cmax, Tmax, AUC0-24 h, AUC0-∞, ke, and t1/2 of the test and reference formulations were 268.4 (78.96) and 256.9 (79.34), 2.750 (0.9555) and 3.104 (1.053), 1 981 (729.2) and 1 872 (604.8), 2228 (697.1) and 2 187 (628.5), 0.1332 (0.02748) and 0.1421 (0.04223), 5.419 (1.110) and 5.442 (2.357), respectively. The 90% confidence intervals for AUC0-24 h and Cmax were 0.9037-1.166 and 0.9169-1.1987, respectively. These results were within the accepted bioequivalence range of 0.80-1.25, which satisfied the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration guidelines. In conclusion, the findings of this study indicate that the 2 formulations of 50 mg atenolol that were tested are bioequivalent. Therefore, these formulations may be prescribed interchangeably., (© Georg Thieme Verlag KG Stuttgart · New York.)

A study was conducted in healthy adults (n = 19) to evaluate the pharmacokinetics of lopinavir/ritonavir when coadministered with efavirenz. Participants were administered lopinavir/ritonavir 400/100 mg alone twice daily (bid) from the morning of day 1 through the morning of day 10, and then lopinavir/ritonavir 500/125 mg bid was coadministered with efavirenz 600 mg every evening (qhs) from the evening of day 10 through day 20. Lopinavir and ritonavir exposures when administered alone versus with efavirenz were determined on days 10 and 20 and compared using point estimates and 90% confidence intervals. The point estimates for the ratios of lopinavir maximum observed plasma concentration (C(max)), plasma concentration prior to morning dosing (C(trough)), and area under the plasma concentration-time curve over a dosing interval (AUC(12)) were 1.121, 0.954, and 1.060, respectively. The lopinavir/ritonavir dose of 500/125 mg bid administered with efavirenz most closely approximates the pharmacokinetic exposure of lopinavir/ritonavir 400/100 mg bid administered alone.

Oropharyngeal candidiasis (OPC) is among the most common opportunistic infections observed in persons infected with human immunodeficiency virus. A once-daily miconazole 50 mg mucoadhesive buccal tablet (MBT) is a novel delivery system with potent in vitro activity against many Candida species, including some that may be resistant to other azoles. MBT, although more expensive, offers an effective, safe, and well-tolerated topical treatment option for OPC that is administered as a convenient once-daily dose.

History: A 60-year-old woman was referred to our hospital, because she was unarousable. She was known to have an impaired liver function due to long-lasting alkohol abuse. Third-party medical history did not explain the patient's condition., Treatment and Course: The history and laboratory findings suggested hepatic coma, therefore treatment with ornithin-aspartat, rifaximin, lactulose and antibiotics was started. Lactate concentration indicated severe hypoxic damage. The clinical examinations and circulatory parameters lead to the diagnosis of sepsis, which was suspected to be caused by spontaneous bacterial peritonitis. Computed tomography of the abomen demonstrated colitis but no other pathologic intestinal finding. Inspite of intensive therapy with antibiotics, fluids and catecholamines the patient died 3 days after admission. Autopsy revealed the cause of sepsis: a tablet, swallowed with its blister package had led to a perforation of the terminal ileum., Conclusion: Apart from the most cause of peritonitis in patients with liver cirrhosis - the spontaneous bacterial peritonitis - a secondary cause must also be taken into account as a reason for sepsis. A well prepared history could possibly show the direction for detection of the cause., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: We aimed to investigate whether the single pill combination (SPC) of aliskiren 300 mg and amlodipine 10 mg (ALIS 300/AMLO 10) improves blood pressure (BP) reduction in hypertensive patients not adequately controlled by the SPC olmesartan 40 mg and amlodipine 10 mg (OLM 40/AMLO 10)., Methods: Open-label, non-randomized single-arm study. Patients with stage 2 hypertension were titrated to the SPC OLM 40/AMLO 10 (4-week Phase 1). If hypertension was not controlled they were switched to the SPC ALIS 300/AMLO 10 (4-week Phase 2). In the optional 4-week study extension hydrochlorothiazide (HCT) 12.5 mg was added. EudraCT 2009-016693-33., Results: In the 342 patients treated, OLM 40/AMLO 10 reduced systolic BP (SBP)/diastolic BP (DBP) by 24.5/14.5 mmHg by end of Phase 1. Those 187 patients with uncontrolled hypertension at the end of Phase 1 switched to ALIS 300/AMLO 10 experienced a further SBP reduction of 5.1 mmHg (95% confidence interval [CI] 3.7 to 6.5, p < 0.0001) and a DBP reduction of 4.8 mmHg (95% CI 3.8 to 5.8; p < 0.0001) in Phase 2. DBP or SBP responder rates were achieved by 51.3% or 44.4%, respectively, SBP and DBP normalization by 36.4%. In 65 patients whose BP was not controlled in Phase 2, SPC ALIS 300/AMLO 10/HCT 12.5 mg decreased SBP/DBP by further 8.1/6.7 mmHg (p < 0.0001 each). No deaths or serious adverse events were noted. Significant adverse events leading to study discontinuation were reported in 2.6% (Phase 1), 2.7% (Phase 2), and 0% (extension). Limitations included the open-label, single-arm non-randomized design, and the relatively short duration., Conclusions: In this switch study reflecting clinical practice, patients with moderate hypertension not controlled by the SPC OLM 40/AMLO 10 achieved a clinically and statistically significant reduction of blood pressure from the SPC ALIS 300/AMLO 10 and the optional addition of HCT. All drug combinations were well tolerated.

Objective: To observe the compliance of film-coated praziquantel tablets in the schistosomiasis transmission controlled areas, so as to provide the evidence for the establishment of chemotherapy intervention measures in these areas., Methods: In the areas of schistosomiasis transmission controlled in Sichuan Province, 234 people were selected as film-coated praziquantel group (FCPG), and 203 people were selected as praziquantel group (PG). A questionnaire survey was implemented and the compliance of chemotherapy of the 2 groups was compared., Results: In PG, all the people indicated that the praziquantel tablets has bad smell, 98.0% of the people had side-effects, such as nausea, headache, 69.5% thought the medicine was harmful to health subjectively, and 99.5% thought that it was too much dose of tablets for taking one time. In FCPG, all the people indicated that the film-coated praziquantel tablets had no bad smell, 18.8% of the people had side-effects, and 74.4% would like to choose film-coated praziquantel tablets. The rates of knowledge of praziquantel of PG and FCPG were 50.7% and 29.1%, respectively ( chi2 = 21.449, P = 0.01)., Conclusions: The film-coated praziquantel tablets have no bad smell and lighter side-effects. The compliance of the film-coated praziquantel tablets is high in the areas of schistosomiasis transmission controlled, so the film-coated praziquantel tablets are worth to popularize and apply.

A 58-year-old female patient was prescribed different drugs in both tablet and powder form and inadvertently ingested the tablet along with its press through package (PTP), which thus became lodged in the subglottic region. An emergency operation was then performed to remove this foreign material, under neuroleptic anesthesia, and the foreign material was removed successfully. Furthermore, no abnormal findings, such as enlarged vocal cords, were noted. Vocal cord granuloma developed three months after the operation but it improved after conservative treatment.

Introduction: Older people in care homes are at increased risk of medication errors and adverse drug events. The effect of formulation on administration errors is not known, that is whether the medicine is a tablet or capsule, liquid or device such as an inhaler. Also, the impact on administration errors of monitored dosage systems (MDS), commonly used in UK care homes to dispense tablets and capsules, is not known. This study investigated the influence of formulation and MDS on administration errors., Methods: Administration errors were identified by pharmacists (using validated definitions) observing two drug rounds of residents randomly selected from a purposive sample of UK nursing and residential homes. Errors were classified and analysed by formulation and medicine delivery system., Results: The odds of administration errors by formulation, when compared with tablets and capsules in MDS, were: liquids 4.31 (95% CI 2.02 to 9.21; p = 0.0002); topicals/transdermals/injections 19.61 (95% CI 6.90 to 55.73; p < 0.0001); inhalers 33.58 (95% CI 12.51 to 90.19; p < 0.0001). The odds of administration errors for tablets and capsules not in MDS were double those that were dispensed in MDS (adjusted OR 2.14, 95% CI 1.02 to 4.51; p = 0.04)., Conclusions: Inhalers and liquid medicines were associated with significantly increased odds of administration errors. Training of staff in safe administration of these formulations needs implementing. Although there was some evidence that MDS reduced the odds of an administration error, the use of MDS impacts on other aspects of medicines management. Because of this, and as the primary topic of our study was not MDS, a prospective trial specifically designed to evaluate the overall impact of MDS on medicine management in care homes is needed.

Background: Efforts to lower plasma lipid levels sometimes require multiple agents with different mechanisms of action to achieve results specified by national treatment guidelines., Methods: This was an open-label, randomized, three-period, multiple-dose crossover study that assessed the potential for pharmacokinetic interaction between extended-release niacin and ezetimibe/simvastatin and their major metabolites. Eighteen adults received three randomized treatments: (A) extended-release (ER) niacin 1000 mg/day for 2 days, followed by 2000 mg/day for 5 days; (B) ezetimibe/simvastatin 10 mg/20 mg/day; (C) coadministration of Treatments A and B. Treatments were given once a day after a low fat breakfast for a total of 7 days, with a 7-day inter-dose period., Results: There were small (mean ≤35%) increases in drug exposure for all analytes after coadministration of ER niacin and ezetimibe/simvastatin 10 mg/20 mg. The least-square mean between treatment C(max) (maximum plasma concentration) ratios (×100) were 97, 98, and 109% for ezetimibe, simvastatin and niacin, respectively. The corresponding ratios for total ezetimibe, simvastatin acid, and nicotinuric acid were 99, 118, and 110%. The AUC((0-24)) (area under the plasma concentration-time curve from time zero to 24 h after dosing) ratios for ezetimibe, simvastatin, and niacin were 109, 120, and 122%, respectively, and the corresponding ratios for total ezetimibe, simvastatin acid, and nicotinuric acid were 126, 135 and 119%., Conclusion: There is a small pharmacokinetic drug interaction between ER niacin and ezetimibe/simvastatin and although this is not considered to be clinically significant, the concomitant use of these drugs should be appropriately monitored, especially during the niacin titration period.

Context: Microcrystalline cellulose (MCC) is extensively used as a filler material in pharmaceutical tablets. When injected intravenously in aqueous tablet suspensions, MCC may contribute to embolic pulmonary hypertension and be identified histologically in lung tissue samples. In this study, we evaluated a modified Russell Movat pentachrome stain (MMPS) as a means of recognizing MCC and distinguishing it from other birefringent crystals in lung specimens., Objective: To study the staining properties of MCC versus other crystalline materials using the MMPS stain., Design: Archival, formalin-fixed, paraffin-embedded lung specimens that contained birefringent crystals, including MCC (3 cases of intravenous drug abuse), talc (2 cases of intravenous drug abuse, 1 talc pleurodesis), mixed silicates (1 case of silicate pneumoconiosis), and calcium oxalate (1 case of aspergillosis from Aspergillus niger infection), were evaluated with MMPS. Crystal identification was confirmed by morphology, other histochemical stains, infrared spectroscopy (1 case), and cellulose controls., Results: The MMPS stained the MCC bright yellow in tissue and control specimens. Talc stained light greenish-blue; mixed silicates appeared either greenish-blue or unstained. Oxalate crystals stained sea-green. Crospovidone, a nonbirefringent tablet filler substance, stained yellow to dark green with MMPS and was easily distinguished from MCC. Starch granules were unstained by MMPS., Conclusions: The MMPS is an excellent method for the histochemical identification of MCC in tissue and its separation from other birefringent crystals with which MCC might be confused. The MMPS is especially useful in the evaluation of pulmonary foreign body embolization in cases of suspected intravenous substance abuse.

Oropharyngeal candidiasis is a commonly encountered problem in daily clinical practice. Topical therapies for oropharyngeal candidiasis are considered preferable to systemic therapies in most patient populations. However, traditional topical therapies have limitations including short contact time with the oral mucosa and the need for multiple doses each day. Miconazole mucoadhesive tablet has recently been approved in Europe (Loramyc®) and the USA (Oravig™) for the treatment of oropharyngeal candidiasis. This tablet adheres to the oral mucosa and provides sustained local release of miconazole over a period of several hours with just one daily application. This article reviews the pharmacology, safety and efficacy of this novel agent.