Effect of omeprazole on the pharmacokinetics of saquinavir-500 mg formulation with ritonavir in healthy male and female volunteers
| Autor: | Alan Winston, Izabela Tolowinska, David Back, Anton Pozniak, Lesley Robinson, Malte Schutz, Jennifer Unsworth, Brian Gazzard, Marta Boffito, Carl Fletcher |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Adolescent medicine.drug_class viruses Immunology Proton-pump inhibitor Pharmacology Dosage form Pharmacokinetics medicine Humans Immunology and Allergy Drug Interactions Protease inhibitor (pharmacology) Saquinavir Omeprazole Ritonavir business.industry Proton Pump Inhibitors HIV Protease Inhibitors Middle Aged biochemical phenomena metabolism and nutrition Anti-Ulcer Agents Infectious Diseases Drug Therapy Combination Female Biological half-life business medicine.drug |
| Zdroj: | AIDS. 20:1401-1406 |
| ISSN: | 0269-9370 |
| DOI: | 10.1097/01.aids.0000233573.41597.8a |
| Popis: | Introduction: Recent studies have described reduced absorption of certain protease inhibitors when administered with agents known to increase gastric pH. No clinically significant interactions between saquinavir absorption and gastric pH have previously been shown. We evaluated the effect of omeprazole, a proton-pump-inhibitor, on the pharmacokinetics of the recently developed saquinavir-500 mg formulation co-administered with ritonavir. Methods: Eighteen healthy subjects (n = 6 women and 12 men) received 1000/100 mg saquinavir/ritonavir twice daily in an open-label study for 15 days. On days 11-15, subjects were administered omeprazole 40 mg daily with the morning dose. Serial plasma samples were collected for 12-h pharmacokinetic profiles of saquinavir and ritonavir on days 10 and 15 and safety analysis on days 1, 4, 10, 15 and 29. Results: The geometric mean and 95% confidence interval (Cl), for the area under time-concentration curve (AUC; ng h/ml), trough plasma concentration (C trough ; ng/ml) and maximum observed plasma concentration (C max ; ng/ml) of saquinavir were 20599 (14396-29360) and 37511 (28733-48970); 737 (482-1127) and 1521 (1039-2227); 3227 (2370-4393) and 5611 (4507-7710) on days 10 and 15, respectively, with geometric mean ratios of1.82, 2.06 and 1.75. No significant changes were observed in saquinavir elimination half life, ritonavir pharmacokinetic parameters or in safety laboratory tests. No unexpected adverse events attributed to study medication were noted. Conclusions: In the presence of omeprazole, total saquinavir plasma exposure is significantly increased (82% increase in AUC). The mechanism of this interaction requires elucidation. Despite the significant increase in saquinavir exposure, no short term toxicities were observed. |
| Databáze: | OpenAIRE |
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