Pharmacokinetics and Bioequivalence Evaluation of 2 Formulations of Tenofovir Alafenamide.

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 (AUC0-t ), area under the concentration-time curve from time 0 to infinity (AUC0-∞ ), and maximum concentration (Cmax ) 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 Cmax , AUC0-t , and AUC0-∞ 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 AUC0-t and AUC0-∞ 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 Cmax 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).