Effect of food on the pharmacokinetics of emtricitabine/rilpivirine/tenofovir disoproxil fumarate single-tablet regimen

Purpose: Emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF; Complera ® /Eviplera ® ) is a recently approved complete single tablet regimen (STR) for treatment-naive HIV-1-infected patients. Exposures of rilpivirine single agent Edurant ® ) are 40% lower when administered under fasted conditions versus standard meal (533 kcal) or high-fat/high caloric meal (928 kcal). The present study evaluated the effect of standard and light meal on FTC/RPV/TDF pharmacokinetics (PK). Methods: This was a three-period, six-sequence, crossover single-dose study (N=24) in healthy subjects that received FTC/RPV/TDF with a standard meal (540 kcal, 21 g fat), light meal (390 kcal, 12 g fat) or under fasted conditions (each treatment 18 days apart). Blood sampling was done for 192 hrs and PK of RPV, FTC, and tenofovir (TFV) were evaluated. Safety was monitored throughout the study and at 14-day follow-up. Exposures of study drugs from the various treatments were compared to fasted or standard meal as reference using 90% confidence interval (CI) bounds of 80 to 125% about the geometric mean ratio (GMR). Results: Of the 24 enrolled subjects, 23 completed. There were no Grade 3 or 4 adverse events (AEs), serious AEs, or AEs leading to discontinuation. Compared to fasting conditions, RPV AUC inf was 9% and 16% higher with a light meal or standard meal, respectively. Compared to standard meal, RPV AUC inf was 14% and 6% lower with fasted or light meal administration, respectively. TFV and FTC exposures were consistent with their established PK/food effect (Table 1). Conclusion: Administration with food has a modest effect on RPV PK as FTC/RPV/TDF STR versus fasted dosing, with no relevant differences between a light meal versus standard meal. FTC/RPV/TDF STR can be administered with a light or standard meal. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Ramanathan S et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18333 http://www.jiasociety.org/index.php/jias/article/view/18333 | http://dx.doi.org/10.7448/IAS.15.6.18333