Effect of varying amounts of a liquid nutritional supplement on the pharmacokinetics of posaconazole in healthy volunteers
| Autor: | Xin Yu, Irene Wu, Lei Ma, Steven Komjathy, Eric Beresford, Edward Power, Gopal Krishna, Donna Vickery |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Pharmacology Posaconazole Antifungal Agents Cross-Over Studies Chemistry Cmax Healthy subjects Biological Availability Triazoles Crossover study Bioavailability Infectious Diseases Animal science Pharmacokinetics Food Healthy volunteers medicine Humans Pharmacology (medical) Female Adverse effect medicine.drug |
| Zdroj: | Antimicrobial agents and chemotherapy. 53(11) |
| ISSN: | 1098-6596 |
| Popis: | The aim of this single-center, phase 1, randomized, 5 by 5 crossover, open-label study was to determine the effects of varying amounts of a nutritional supplement (Boost Plus) on the pharmacokinetics of posaconazole in 30 healthy volunteers. After an overnight fast, subjects were administered a single dose of 400 mg posaconazole oral suspension alone or following Boost Plus (8 fluid ounces [oz] [240 ml], 4 oz [120 ml], 2 oz [60 ml], or 1 oz [30 ml]). Subjects were randomized to receive all five treatments in different sequences, with a 14-day washout between treatments. Primary pharmacokinetic variables—area under the concentration-time curve from time zero to the time of the final quantifiable sample (AUC tf ), maximum observed plasma concentration ( C max ), time to C max ( T max ), and relative bioavailability—were assessed up to 5 days postdose. Safety assessments included testing for adverse events, clinical laboratory tests, measurement of vital signs, physical examinations, and electrocardiograms. Posaconazole bioavailability increased almost linearly with increasing amounts of Boost Plus. Based on log-transformed data, the relative bioavailabilities (AUCs) of posaconazole were 35% (fasting), 48% (1 oz), 60% (2 oz), and 77% (4 oz) of the level reached in the presence of 8 oz Boost Plus, whereas T max was unaffected. Compared with the levels reached under fasting conditions, posaconazole C max and AUC values increased 3.5- and 2.9-fold, respectively, when given with 8 oz Boost Plus. Single doses of posaconazole at 400 mg alone and with 1, 2, 4, or 8 oz Boost Plus were safe and well tolerated in healthy subjects. |
| Databáze: | OpenAIRE |
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