Effect of Food on the Pharmacokinetics of Tenofovir Amibufenamide: A Phase I, Randomized, Open-Label, Two-Period Crossover Trial in Healthy Adult Subjects.

ABSTRACT

Purpose: Tenofovir amibufenamide (TMF) is a novel nucleotide reverse transcriptase inhibitor. The aim of this study was to investigate the effect of food on the single-dose pharmacokinetic properties of TMF. Patients and Methods: In this open-label, randomized, crossover study, after an overnight fast, eligible subjects received a single 25 mg dose of TMF tablet, either under fasted conditions or following consumption of a high-fat, high-calorie meal, followed by a two-week washout period. Blood samples were collected until 144 h after administration. TMF and its metabolite, tenofovir (TFV), were analyzed using validated liquid chromatography-tandem mass spectrometry methods. The geometric mean ratio (GMR) and the corresponding 90% confidence interval (CI) values of AUC0-t, AUC0-∞, and Cmax were acquired for analysis. The absence of an effect of food was indicated if the 90% CI values were within the predefined equivalence limits of 80%-125%. Safety and tolerability were also assessed. Results: For TMF, adjusted GMR (90% CI) values for the fed versus fasted states were 150.28% (125.36%-180.16%), 158.24% (130.42%-192.00%), and 57.65% (45.68%-72.76%) for AUC0-t, AUC0-∞, and Cmax, respectively. For TFV, the GMR (90% CI) of Cmax was 82.00% (74.30%-90.49%) after administration under fed conditions, slightly outside the bioequivalence boundary of 80%-125%, while the corresponding values for AUC0-t and AUC0-∞ were within range. The absorption of TMF was delayed by food, with median Tmax values of 0.33 and 1.00 h in fasted and fed conditions, respectively. The adverse events observed in subjects were all mild. Conclusion: Our results demonstrated that TMF tablets were well-tolerated in healthy volunteers. When TMF tablets were taken with food, Tmax was delayed and exposures of TMF and TFV were higher than under fasted conditions. The modest changes observed are not considered clinically relevant, so TMF can be taken with or without food.