European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
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Randomized Controlled Trial
Pharmacokinetic and pharmaceutical properties of a novel buprenorphine/naloxone sublingual tablet for opioid substitution therapy versus conventional buprenorphine/naloxone sublingual tablet in healthy volunteers.
A novel sublingual buprenorphine/naloxone rapidly-dissolving tablet (BNX-RDT) for opioid substitution therapy has been developed for improved bioavailability, rapid disintegration and improved taste masking. We compared the bioavailability and pharmaceutical properties of BNX-RDT with conventional buprenorphine/naloxone sublingual tablets (BNX). ⋯ BNX-RDT provided improved buprenorphine absorption compared to a conventional sublingual tablet, with shorter dissolve times and improved taste and mouthfeel, resulting in a high preference for the novel formulation.
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Randomized Controlled Trial
Population pharmacokinetic evaluation of ADV6209, an innovative oral solution of midazolam containing cyclodextrin.
In the absence of a licensed formulation in many countries worldwide, ADV6209, an innovative 2mg/ml oral solution of midazolam containing cyclodextrin, has been developed for moderate sedation in paediatric patients. Population pharmacokinetics for ADV6209 is reported. ⋯ Pharmacokinetic parameters were close to those reported in the literature with midazolam extemporaneous oral solutions or syrups, demonstrating that cyclodextrin had no significant effect on measured parameters.
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Randomized Controlled Trial Multicenter Study
A PK-PD model-based assessment of sugammadex effects on coagulation parameters.
Exposure-response analyses of sugammadex on activated partial thromboplastin time (APTT) and prothrombin time international normalized ratio (PT(INR)) were performed using data from two clinical trials in which subjects were co-treated with anti-coagulants, providing a framework to predict these responses in surgical patients on thromboprophylactic doses of low molecular weight or unfractionated heparin. Sugammadex-mediated increases in APTT and PT(INR) were described with a direct effect model, and this relationship was similar in the presence or absence of anti-coagulant therapy in either healthy volunteers or surgical patients. In surgical patients on thromboprophylactic therapy, model-based predictions showed 13.1% and 22.3% increases in respectively APTT and PT(INR) within 30min after administration of 16mg/kg sugammadex. These increases remain below thresholds seen following treatment with standard anti-coagulant therapy and were predicted to be short-lived paralleling the rapid decline in sugammadex plasma concentrations.
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Randomized Controlled Trial
Influence of genetic polymorphisms on the pharmacokinetics of celecoxib and its two main metabolites in healthy Chinese subjects.
Celecoxib is a selective cyclooxygenase-2 inhibitor used extensively for the treatment of rheumatism and osteoarthritis. The aim of this study was to evaluate the influence of the genetic polymorphisms of CYP2C9, CYP2D6 and CYP3A4 on the pharmacokinetics (PK) of celecoxib and its two main metabolites, hydroxyl-celecoxib and carboxy-celecoxib, in healthy Chinese subjects, based on a bioequivalence study of celecoxib. This study was an open-label, two-period, crossover study. 52 healthy Chinese male subjects were recruited and were genotyped for CYP2C9*3, CYP2C9*13, CYP2D6*10 and CYP3A4*18 by using polymerase chain reactions (PCR). ⋯ In terms of carboxy-celecoxib, the AUC0-48 was increased by 25.2%, the t1/2 prolonged 16.1% and the CL/F was decreased by 21.2% in CYP2C9*1/*3 group. Except for the t1/2 of hydroxy-celecoxib, no statistically significant difference was observed in other pharmacokinetic parameters of hydroxy-celecoxib and carboxy-celecoxib between the two CYP2C9 genotypic groups. This study revealed that there was no significant influence of CYP2D6*10 on the metabolism of celecoxib, and the expression of CYP2C9*3 led to increased drug exposure and slowed drug disposition in healthy Chinese male subjects.
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Randomized Controlled Trial Clinical Trial
Novel method to assess gastric emptying in humans: the Pellet Gastric Emptying Test.
To further validate the Pellet Gastric Emptying Test (PGET) as a marker of gastric emptying, a randomized, four-way crossover study was conducted with 12 healthy subjects. The study consisted of oral co-administration of enteric coated caffeine (CAFF) and acetaminophen (APAP) pellets in four treatment phases: Same Size (100 kcal), Fasted, Small Liquid Meal (100 kcal), and Standard Meal (847 kcal). The time of first appearance of measurable drug marker in plasma, t(initial), was taken as the emptying time for the markers. ⋯ Co-administration of different size pellets indicated that the smaller 0.7-mm diameter (CAFF) pellets were emptied and absorbed significantly earlier than the larger 3.6-mm diameter (APAP) pellets with both the Small Liquid Meal (by 35 min) and the Standard Meal (by 33 min) (P<0.05). The differences in emptying of the pellets were not significant in the Fasted Phase. The results suggest that the pellet gastric emptying test could prove useful in monitoring changes in transit times in the fasted and fed states and their impact on drug absorption.