Pharmacokinetics and Bioequivalence Evaluation of 2 Formulations of Tenofovir Alafenamide

Abstract

Abstract The study was conducted to compare the pharmacokinetics and safety profiles of 2 brands of tenofovir alafenamide (TAF) fumarate tablets. This research was a 2‐preparation, 2‐sequence, 4‐period crossover, completely replicated study in 68 healthy Chinese subjects under fasting and fed conditions. The mean values of the area under the concentration‐time curve from time 0 to the last time point with blood sample collection (AUC 0‐t ), area under the concentration‐time curve from time 0 to infinity (AUC 0‐∞ ), and maximum concentration (C max ) for the test and reference products of TAF were 248.5 and 275.7 ng/mL, 148.1 and 157.8 ng • h/mL, and 148.4 and 158.1 ng • h/mL, respectively, under the fasting condition. On the other hand, the mean value of C max , AUC 0‐t , and AUC 0‐∞ for the test and reference formulations of TAF were 244.6 and 246.7 ng/mL, 230.4 and 244.9 ng • h/mL, and 233.2 and 246.2 ng • h/mL, respectively, under the fed condition. The 90% confidence intervals for geometric mean ratios of AUC 0–t and AUC 0‐∞ of TAF in fasting and fed states were within the bioequivalence acceptance limits when tested using the average‐bioequivalence method. The point estimate value for geometric mean ratio of C max in fasting and fed states (88.4% and 95.5%, respectively) were within the bioequivalence acceptance limits as per the reference‐scaled average‐bioequivalence method. The safety profiles of the 2 formulations were comparable. Pharmacokinetic analysis demonstrated that the test formulations of TAF exhibited bioequivalence to the reference and were well tolerated by healthy Chinese subjects (Study Registry Identification Number: CTR20190086; CTR20190087).