Open AccessEffect of food on the pharmacokinetics of emtricitabine/rilpivirine/tenofovir disoproxil fumarate single‐tablet regimen
Author(s) -
Ramanathan S,
Custodio J,
Yin X,
Hepner M,
Pugatch D,
Kearney B
Publication year - 2012
Publication title -
journal of the international aids society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.724
H-Index - 62
ISSN - 1758-2652
DOI - 10.7448/ias.15.6.18333
Subject(s) - rilpivirine , medicine , emtricitabine , pharmacokinetics , meal , adverse effect , regimen , pharmacology , human immunodeficiency virus (hiv) , viral load , virology , antiretroviral therapy
Purpose Emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF; Complera®/Eviplera®) is a recently approved complete single tablet regimen (STR) for treatment‐naïve 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).Exposure versus standard mealGMR (%) 90% CI fasted/standard GMR (%) 90% CI light meal/standardRilpivirineAUC inf (ng*h/mL) 85.9 (72.7, 101) 93.8 (79.2, 111) AUC last (ng*h/mL) 83.7 (70.6, 99.3) 94.9 (79.9, 113) C max (ng/mL) 79.1 (65.5, 95.5) 106 (87.6, 129)EmtricitabineAUC inf (ng*h/mL) 105 (102, 108) 101 (98.2, 104) AUC last (ng*h/mL) 105 (102, 108) 101 (98.2, 104) C max (ng/mL) 107 (101, 114) 103 (96.2, 109)TenofovirAUC inf (ng*h/mL) 72.5 (68.1, 77.2) 93.0 (87.2, 99.2) AUC last (ng*h/mL) 70.9 (66.3, 75.8) 92.8 (86.7, 99.4) C max (ng/mL) 75.8 (67.8, 84.6) 84.8 (75.8, 94.9)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.