The Effect of Food on Doravirine Bioavailability: Results from Two Pharmacokinetic Studies in Healthy Subjects.

BACKGROUND AND OBJECTIVE: Doravirine is a novel non-nucleoside reverse transcriptase inhibitor being developed for the treatment of HIV-1. In two open-label, single-dose, randomized, two-period, crossover trials, the bioavailability of doravirine administered alone or in a fixed-dose combination (FDC) was determined under fed and fasted conditions.

METHODS: Doravirine 100 mg alone or with lamivudine and tenofovir disoproxil fumarate (each 300 mg) were administered to healthy subjects fasted or 30 min after a high-fat, high-calorie breakfast. Twenty-eight subjects, aged 26-55 years, enrolled (doravirine, n = 14; FDC, n = 14). The sequence of fed/fasted treatment was randomized (1:1). Pharmacokinetic data were analyzed as geometric mean ratios (GMRs) with 90% confidence intervals.

RESULTS: Doravirine area under the plasma concentration-time curve (AUC) from time zero to infinity (fed/fasted GMRs: alone 1.16 [1.06-1.26]; FDC 1.10 [1.02-1.20]), AUC from time zero to the last measurement (GMRs: alone 1.18 [1.08-1.29]; FDC 1.10 [1.01-1.20]), and plasma concentration 24 h after administration (GMRs: alone 1.36 [1.19-1.55]; FDC 1.26 [1.13-1.41]) values increased in the fed versus fasted state when administered alone or as the FDC; the magnitude was not clinically meaningful. Doravirine maximum achieved concentration was similar after fed or fasted administration for both doravirine alone and FDC (GMRs: alone 1.03 [0.89-1.19]; FDC 0.95 [0.80-1.12]). The pharmacokinetics of tenofovir and lamivudine in the FDC were also slightly altered by administration with food; the changes were not clinically meaningful.

CONCLUSIONS: All treatments were generally well tolerated. Food had no clinically meaningful effect on doravirine 100 mg alone or as part of an FDC.