title: 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.
abstract: 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.
authors.affiliation: Clinical Development Department, Pharmaceutical Division, Japan Tobacco Inc., Tokyo, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Shiomi
authors.affiliation: Medical Co. LTA Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Matsuki
authors.affiliation: Clinical Development Department, Pharmaceutical Division, Japan Tobacco Inc., Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ikeda
authors.affiliation: Clinical Development Department, Pharmaceutical Division, Japan Tobacco Inc., Tokyo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Clinical Development Department, Pharmaceutical Division, Japan Tobacco Inc., Tokyo, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Nishino
authors.affiliation: Medical Co. LTA Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Clinical Research Center, Kitasato University, Kanagawa, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kumagai
authors.affiliation: Medical Co. LTA Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Irie
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D000069547:Cobicistat / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000069545:Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D007564:Japan; D016018:Least-Squares Analysis; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D015363:Quinolones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D013607:Tablets; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D000069545:Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; D015363:Quinolones; D013607:Tablets; C509700:elvitegravir; D000069547:Cobicistat
keywords: HIV integrase strand transfer inhibitor; Japanese; bioequivalence; elvitegravir; stribild