Pharmacokinetic and bioequivalence evaluation of single‐tablet and separate‐tablet regimens for once‐daily cobicistat‐boosted elvitegravir in healthy Japanese male subjects: A randomized, two‐way crossover study
| Autor: | Atsushi Ikeda, Miyuki Kimura, Tomohiro Ishikawa, Yuji Kumagai, Shin Irie, Noriaki Nishino, Mari Shiomi, Shunji Matsuki |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Anti-HIV Agents Metabolic Clearance Rate Cmax Administration Oral Pharmaceutical Science Quinolones Pharmacology Bioequivalence Emtricitabine Models Biological Drug Administration Schedule Young Adult Japan Humans Medicine Pharmacology (medical) Least-Squares Analysis Cross-Over Studies business.industry Elvitegravir Cobicistat Middle Aged Crossover study Healthy Volunteers Regimen Therapeutic Equivalency Tolerability Area Under Curve Elvitegravir Cobicistat Emtricitabine Tenofovir Disoproxil Fumarate Drug Combination Drug Therapy Combination business Tablets medicine.drug |
| Zdroj: | Clinical Pharmacology in Drug Development. 4:218-225 |
| ISSN: | 2160-7648 2160-763X |
| Popis: | This randomized, two-way crossover study evaluated the bioavailability of elvitegravir administered as the new individual tablet containing 150 mg and a cobicistat 150 mg tablet, concomitantly with a fixed-dose combination tablet containing 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate (EVG + COBI + FTC/TDF), in comparison with a single-tablet regimen containing the same dose of each component (EVG/COBI/FTC/TDF). Twenty-four healthy Japanese male subjects received the two different elvitegravir treatments, the separate-tablet or single-tablet regimen, once-daily for 10 days in each. The pharmacokinetic parameters (Cmax , AUCtau , and Ctau ) of elvitegravir were investigated at Day 10 after each treatment, together with safety and tolerability. Relative to EVG/COBI/FTC/TDF, the geometric least-squares mean ratios (GMR) and 90% confidence intervals (CIs) for elvitegravir Cmax and AUCtau were within the boundary of 0.8-1.25, while the upper limit of the 90% CI of GMR for Ctau was narrowly below the lack of bioequivalence boundary (0.79). No deaths, serious AEs, or drug-related AEs occurred. In conclusion, Cmax and AUCtau of elvitegravir met the strict definition of bioequivalence, indicating that the two regimens were essentially bioequivalent. Treatment with both regimens for 10 days appeared to be safe and well tolerated. |
| Databáze: | OpenAIRE |
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