Bioavailability and bioequivalence of a darunavir 800-mg tablet formulation compared with the 400-mg tablet formulation
| Autor: | Frank Tomaka, Maarten Timmers, Vera Hillewaert, Richard M. W. Hoetelmans, Thomas N. Kakuda, Lorant Leopold, Tom Van De Casteele |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Adolescent Anti-HIV Agents Metabolic Clearance Rate Chemistry Pharmaceutical Administration Oral Biological Availability Pharmacology Bioequivalence Drug Administration Schedule Young Adult Pharmacokinetics Humans Medicine Pharmacology (medical) Least-Squares Analysis Darunavir Sulfonamides Cross-Over Studies Ritonavir business.industry Half-life Fasting Middle Aged Postprandial Period Crossover study Healthy Volunteers Bioavailability Therapeutic Equivalency Tolerability Area Under Curve Drug Therapy Combination Female business Half-Life Tablets medicine.drug |
| Zdroj: | Int. Journal of Clinical Pharmacology and Therapeutics. 52:805-816 |
| ISSN: | 0946-1965 |
| DOI: | 10.5414/cp202066 |
| Popis: | UNLABELLED Once-daily darunavir/ritonavir (800/100 mg), plus other antiretrovirals, is recommended for HIV-1-infected patients. Low therapy adherence is linked with poor outcomes. Pill burden can impact adherence. An 800-mg darunavir tablet would reduce pill burden. OBJECTIVES To assess the relative oral bioavailability (NCT01052883) and bioequivalence (NCT01308658) of a darunavir 800-mg tablet vs. 2 × 400-mg tablets. METHODS In two phase I, open-label, randomized, crossover, single-center studies, healthy volunteers received once-daily ritonavir (100 mg, days 1 - 5) and a single 800-mg darunavir dose: 2 × 400-mg tablets (reference) or 1 × 800- mg tablet (test) on day 3 and vice versa after a ≥ 7-day wash-out. Each study had fasted (n = 16 (bioavailability); n = 83 (bioequivalence)) and fed panels (n = 16; n = 45, respectively). Pharmacokinetic profiles and tolerability were assessed. RESULTS No volunteers discontinued for treatment-related reasons. Least-square mean ratios (test vs. reference) for darunavir maximum plasma concentrations (C(max)), area under the concentration-time curve from zero to infinity (AUC(0-∞)) were: 1.06 and 1.15 (bioavailability), and 1.02 and 1.00 (bioequivalence), respectively (fasted); 0.89 and 0.88 (bioavailability), and 0.96 and 0.98 (bioequivalence), respectively (fed). 90% confidence intervals (CI) were within 80.00 - 125.00%, except bioavailability AUC(0-∞) (fed and fasted conditions). Median time to C(max) was comparable for both formulations. No clinically relevant differences in adverse events or laboratory abnormalities occurred between formulations. CONCLUSIONS Bioequivalence was demonstrated for the 800-mg darunavir tablet (fasted and fed conditions). This formulation can reduce pill burden and potentially increase adherence for HIV-1-infected patients in whom once-daily darunavir/ritonavir 800/100 mg is appropriate. |
| Databáze: | OpenAIRE |
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