Pharmacokinetics of Tenofovir Alafenamide, Tenofovir, and Emtricitabine Following Administration of Coformulated Emtricitabine/Tenofovir Alafenamide in Healthy Japanese Subjects.

ABSTRACT

A fixed-dose combination of tenofovir alafenamide (TAF) and emtricitabine (FTC) is available in 2 tablet strengths in Japan (FTC/TAF 200/10 mg and FTC/TAF 200/25 mg). These are used once daily in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 infection. The primary objective of this study was to investigate if there is any clinically relevant pharmacokinetic difference for TAF, tenofovir (TFV), and FTC between Japanese and non-Japanese with historical data. Three treatment groups were set in the study; FTC/TAF 200/10 mg in combination with darunavir (DRV) 800 mg + ritonavir (RTV) 100 mg (treatment A) or DRV/cobicistat (COBI) 800/150 mg (treatment B) and FTC/TAF 200/25 mg alone (treatment C). Especially for treatment C, it was designated for another purpose to evaluate the pharmacokinetic boosting effects of RTV and COBI on TAF bioavailability. As a result, the mean exposure of TAF among treatment groups was 125 to 154 ng/mL for Cmax and 119 to 179 ng·h/mL for AUCinf , which were comparable with the historical data in non-Japanese. The exposures of TFV and FTC were also consistent with the historical data. Therefore, no clinically relevant pharmacokinetic differences for TAF, TFV, and FTC were observed between Japanese and non-Japanese. Boosting effects of RTV and COBI on TAF bioavailability were slightly lower than we expected, less than a 2.5-fold increase, but it was within the range of exposures associated with efficacy and safety in phase 3 studies. Therefore, it was not considered clinically relevant.