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. Issue 3 (27th October 2014)

• Record Type: Journal Article
• Authors: Shiomi, Mari; Matsuki, Shunji; Ikeda, Atsushi; Ishikawa, Tomohiro; Nishino, Noriaki; Kimura, Miyuki; Kumagai, Yuji; Irie, Shin
• Is Part Of: Clinical pharmacology in drug development. Volume 4:Issue 3(2015:May/Jun.)
• Page Start: 218
• Page End: 225
• Publication Date: 2014-10-27
• Subjects: Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.164
• Languages: English
• ISSNs: 2160-7648

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="cpdd164-sec-0001" sec-type="section"> <p>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 (C<sub>max</sub>, AUC<sub>tau</sub>, and C<sub>tau</sub>) 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 C<sub>max</sub> and AUC<sub>tau</sub> were within the boundary of 0.8–1.25, while the upper limit of the 90% CI of GMR for C<sub>tau</sub> was narrowly below the lack of bioequivalence boundary (0.79). No deaths, serious AEs, or drug‐related AEs occurred. In conclusion, C<sub>max</sub> and AUC<sub>tau</sub> 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.</p> </sec> </abstract>