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To investigate the effect of simulated weightlessness on the pharmacokinetics of orally administered moxifloxacin and the antacid Maalox or the antidiarrheal Pepto-Bismol using a tail-suspended (TS) rat model of microgravity. Fasted control and TS, jugular-vein-cannulated, male Sprague-Dawley rats received either a single 5 mg/kg intravenous dose or a single 10 mg/kg oral dose of moxifloxacin alone or with a 0.625 mL/kg oral dose of Maalox or a 1.43 mL/kg oral dose of Pepto-Bismol. Plasma concentrations of moxifloxacin were measured by HPLC. Pharmacokinetic data were analyzed using WinNonlin. Simulated weightlessness had no effect on moxifloxacin disposition after intravenous administration but significantly decreased the extent of moxifloxacin oral absorption. The coadministration of moxifloxacin with Maalox to either control or TS rats caused significant reductions in the rate and extent of moxifloxacin absorption. In contrast, the coadministration of moxifloxacin with Pepto-Bismol to TS rats had no significant effect on either the rate or the extent of moxifloxacin absorption. These interactions showed dose staggering when oral administrations of Pepto-Bismol and moxifloxacin were separated by 60 min in control rats but not in TS rats. Dose staggering was more apparent after the coadministration of Maalox and moxifloxacin in TS rats.

Layered double hydroxides (LDHs), have been known for many decades as catalyst and ceramic precursors, traps for anionic pollutants, and additives for polymers. Recently, their successful synthesis on the nanometer scale opened up a whole new field for their application in nanomedicine. Here we report the efficacy of Mg1-xAlx (NO3)x (OH)2 LDH nanoparticles as a carrier and for controlled release of one of the non-steroidal anti-inflammatory drugs (NSAID), sodium salicylate. Mg1-xAlx (NO3)x (OH)2.nH2O nanoparticles were synthesized using co-precipitation method from an aqueous solution of Mg(NO3)2.6H2O and Al(NO3)3.9H2O. Salicylate was intercalated in the interlayer space of Mg-Al LDH after suspending nanoparticles in 0.0025(M) HNO3 and 0.75 (M) NaNO3 solution and using anion exchange method under N2 atmosphere. The shift in the basal planes like (003) and (006) to lower 2θ value in the XRD plot of intercalated sample confirmed the increase in basal spacing in LDH because of intercalation of salicylate into the interlayer space of LDH. FTIR spectroscopy of SA-LDH nano hybrid revealed a red shift in the frequency band of carboxylate group in salicylate indicating an electrostatic interaction between cationic LDH sheet and anionic drug. Differential thermal analysis of LDH-SA nanohybrid indicated higher thermal stability of salicylate in the intercalated form into LDH as compared to its free state. DLS studies showed a particle size distribution between 30-60 nm for pristine LDH whereas salicylate intercalated LDH exhibited a particle size distribution between 40-80nm which is ideal for its efficacy as a superior carrier for drugs and biomolecules. The cumulative release kinetic of salicylate from MgAl-LDH-SA hybrids in phosphate buffer saline (PBS) at pH7.4 showed a sustained release of salicylate up to 72h that closely resembled first order release kinetics through a combination of drug diffusion and dissolution of LDH under physiological conditions. Also the cytotoxicity tests performed revealed the less toxic nature of the nanohybrid as compared to the bare SA drug., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al(3+) in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.

The intercalation of a drug active, perindopril, into Mg/Al-layered double hydroxide for the formation of a new nanocomposite, PMAE, was accomplished using a simple ion exchange technique. A relatively high loading percentage of perindopril of about 36.5% (w/w) indicates that intercalation of the active took place in the Mg/Al inorganic interlayer. Intercalation was further supported by Fourier transform infrared spectroscopy, and thermal analysis shows markedly enhanced thermal stability of the active. The release of perindopril from the nanocomposite occurred in a controlled manner governed by pseudo-second order kinetics. MTT assay showed no cytotoxicity effects from either Mg/Al-layered double hydroxide or its nanocomposite, PMAE. Mg/Al-layered double hydroxide showed angiotensin-converting enzyme inhibitory activity, with 5.6% inhibition after 90 minutes of incubation. On incubation of angiotensin-converting enzyme with 0.5 μg/mL of the PMAE nanocomposite, inhibition of the enzyme increased from 56.6% to 70.6% at 30 and 90 minutes, respectively. These results are comparable with data reported in the literature for Zn/Al-perindopril.

Aims: Oseltamivir is an oral ester prodrug of its active metabolite Ro 64-0802, a potent and selective neuraminidase inhibitor of the influenza virus. The object of this study was to evaluate whether the oral absorption of oseltamivir was reduced in the presence of two main classes of antacid, Maalox(R) suspension (containing magnesium hydroxide and aluminium hydroxide) and Titralac(R) tablets (containing calcium carbonate)., Methods: Twelve healthy volunteers completed a randomized, single dose, three-period crossover study. Each volunteer received in a fasted state, 150 mg oseltamivir alone (Treatment A), 150 mg oseltamivir with a 20 ml Maalox suspension (Treatment B), and 150 mg oseltamivir with four Titralac tablets (Treatment C), with 7-10 days washout in between treatments. Plasma and urine concentrations of oseltamivir and Ro 64-0802 were measured using a validated h.p.l.c./MS/MS assay. Pharmacokinetic parameters were calculated for oseltamivir and Ro 64-0802. Since antacids are locally acting drugs and generally not expected to be absorbed substantially into the systemic system, no plasma or urine concentrations of antacids were measured., Results: Bioequivalence was achieved for the primary pharmacokinetic parameters Cmax and AUC(0, infinity ) of Ro 64-0802 following administration of oseltamivir with either Maalox suspension or Titralac(R) tablets vs administration of oseltamivir alone. The bioavailability (90% confidence intervals) of Ro 64-0802 following administration of oseltamivir together with Maalox suspension vs administration of oseltamivir alone, was 90% (83.6, 96.9%) for C(max) and 94.1% (91.4, 96.9%) for AUC(0, infinity); similarly, for Titralac tablets, the equivalent values were 95.1% (88.3, 102%) for C(max) and 94.7% (91.9, 97.5%) for AUC(0, infinity)., Conclusions: The coadministration of either Maalox suspension or Titralac tablets with oseltamivir has no effect on the pharmacokinetics of either oseltamivir or Ro 64-0802, and conversely, there is no evidence that coadministration with oseltamivir has an effect on the safety and tolerability of either Maalox suspension or Titralac tablets. There was no pharmacokinetic interaction between oseltamivir with either antacid, demonstrating that the oral absorption of oseltamivir was not impaired in the presence of antacids containing magnesium, aluminium or calcium.

Macrophagic myofasciitis (MMF) is an emerging condition of unknown cause, detected in patients with diffuse arthromyalgias and fatigue, and characterized by muscle infiltration by granular periodic acid-Schiff's reagent-positive macrophages and lymphocytes. Intracytoplasmic inclusions have been observed in macrophages of some patients. To assess their significance, electron microscopy was performed in 40 consecutive cases and chemical analysis was done by microanalysis and atomic absorption spectrometry. Inclusions were constantly detected and corresponded to aluminium hydroxide, an immunostimulatory compound frequently used as a vaccine adjuvant. A lymphocytic component was constantly observed in MMF lesions. Serological tests were compatible with exposure to aluminium hydroxide-containing vaccines. History analysis revealed that 50 out of 50 patients had received vaccines against hepatitis B virus (86%), hepatitis A virus (19%) or tetanus toxoid (58%), 3-96 months (median 36 months) before biopsy. Diffuse myalgias were more frequent in patients with than without an MMF lesion at deltoid muscle biopsy (P < 0.0001). Myalgia onset was subsequent to the vaccination (median 11 months) in 94% of patients. MMF lesion was experimentally reproduced in rats. We conclude that the MMF lesion is secondary to intramuscular injection of aluminium hydroxide-containing vaccines, shows both long-term persistence of aluminium hydroxide and an ongoing local immune reaction, and is detected in patients with systemic symptoms which appeared subsequently to vaccination.

It is now becoming common practice to co-administer H2-receptor antagonists and anti-reflux agents in the treatment of reflux oesophagitis. The mechanism by which anti-reflux agents achieve flotation requires a small amount of gastric acid to be present in the stomach. This study investigated whether an anti-reflux agent would remain effective after the decrease in acid secretion produced by a typical clinical dosage regimen of cimetidine (400 mg q.d.s., 7 days). Gastric distribution and residence of a meal and an anti-reflux agent were assessed in 12 normal subjects using gamma scintigraphy. The area under the gastric and fundal emptying curves demonstrated that Liquid Gaviscon (sodium alginate compound) had a significantly greater gastric residence than the meal, both during the control period and after cimetidine pretreatment, and that the majority of the Gaviscon was located in the fundus. The distribution of Gaviscon into the fundus was not affected by cimetidine pretreatment. Cimetidine pre-treatment slightly, but not significantly, increased the time for half the meal and the Gaviscon to empty from the stomach. The results suggest that the mechanism of action of Liquid Gaviscon is not compromised by concurrent H2-antagonist therapy.

The rate of gastric emptying of two antacids, magaldrate and Maalox, was investigated using scintigraphy. Successful labelling of the antacids was carried out with 99mTc. The stability of the 99mTc-labelled antacids was satisfactory and there was no difference in antacid capacity between the labelled and unlabelled antacids. The studies were carried out on 15 healthy male volunteers. After an eight hour fast each subject ingested a standardised meal of 95.7 MJ (400 kcal). One hour later 10 ml of one of the two antacids previously labelled with 99mTc was administered. Serial detection by anterior and posterior projection of the amount of antacid retained in the stomach was performed to determine gastric emptying of antacid. One week later the study was repeated under the same conditions with the other antacid also labelled with 99mTc. The mean (SD) percentages of antacid retained in the stomach fit a linear model with a t1/2 of 86.6 (15.3) minutes for magaldrate and 52.3 (5.2) minutes for Maalox (p less than 0.01). When the mean percentages of retention at six time intervals were compared for both antacids, it was found that Maalox emptied much faster (p less than 0.01 at 15 and 30 minutes, p less than 0.02 at 45, 60, 75, and 90 minutes).

The risk of aluminum (Al) accumulation in patients with chronic renal failure has led to use of non-Al phosphate binders. Frequently, Al and non-Al phosphate binders are co-administered. Unfortunately, calcium citrate (Ca citr), when given with Al-gel, markedly enhances Al absorption. To determine whether calcium acetate (Ca acetate) also augments Al absorption, 10 normal volunteers were each given orally, three-day courses of the following drug combinations dosed four times daily: 1) aluminum hydroxide gel (Al[OH]3) (5 ml) alone; 2) Al[OH]3 (5 ml) plus Ca acetate (1330 mg); 3) Al[OH]3 (5 ml) plus Ca citr (950 mg). A nine day wash-out occurred between each course. Al levels were measured using flameless atomic absorption spectrophotometry. Daily urine Al excretion was measured during a two-day baseline before each course and during each three-day drug course. Plasma Al was obtained during each baseline and drug course. Mean 24-hour Al excretion (micrograms/g creatinine/day) at baseline versus treatment for each combination was: 1) 5.9 +/- 3.2 versus 42.0 +/- 40.7 (mean +/- SD); 2) 5.7 +/- 3.0 versus 40.3 +/- 28.6: 3) 6.3 +/- 3.4 versus 175.8 +/- 103.3. Al excretion was significantly greater with combination 3 than with either 1 or 2 (P less than 0.05). The difference between 1 and 2 was not significant. Plasma Al (micrograms/liter) at baseline versus treatment for each combination was: 1) 5.3 +/- 4.2 versus 8.1 +/- 2.5 (mean +/- SD); 2) 3.1 +/- 2.2 versus 7.3 +/- 2.9; 3) 3.0 +/- 2.3 versus 12.0 +/- 6.1.(ABSTRACT TRUNCATED AT 250 WORDS)