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 concentrationtime 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).

Pharmacokinetics, Bioequivalence, and Safety Evaluation of Two Formulations of 0.2‐g Ibuprofen Granules

“…Formulations with greater than 30% intrasubject variability for a PK parameter (C max , AUC 0-t , and AUC 0-∞ ) are considered as highly variable drug products. 17,18 This trial verified the intraindividual variations of the PK parameters of ibuprofen. In both fasting and fed arms, the coefficient of variation values of PK parameters (C max , AUC 0-t , and AUC 0-∞ ) for the test and reference formulations were all less than 30%.…”

“…Formulations with greater than 30% intrasubject variability for a PK parameter (C max , AUC 0‐t , and AUC 0‐∞ ) are considered as highly variable drug products 17,18 . This trial verified the intraindividual variations of the PK parameters of ibuprofen.…”

Population Pharmacokinetics of Tenofovir Alafenamide Fumarate and Its Metabolite Tenofovir in Healthy Chinese Volunteers

“…The formal trial involved 4-periods, 2 formulations, and 2 sequences in a fully repeated crossover trial design, with 67 volunteers completing the trial. 4 The pretrial was conducted using a 3-periods, partially repeated crossover trial design with a single oral administration after consuming a high-fat meal. It was completed in 2019 at the Phase I Clinical Trial Institution of the Second Hospital of Lanzhou University, with 15 volunteers completing the trial.…”

“…A high-fat diet can increase its absorption. 4 The plasma protein-binding rate of TAF exceeds 80%, and within the dose range of 8-120 mg, TAF exposure is linearly related to dosage. 5 Most TAF is converted into TFV in liver cells and subsequently phosphorylated into the active metabolite tenofovir diphosphate, with only less than 1% excreted in the urine in an unchanged form.…”

“…The elimination half-life of TAF is 0.4 hours, and the half-life of the metabolite TFV is 31 hours. 4 Compared with tenofovir disoproxil fumarate (TDF), a prodrug of TFV, TAF can strongly inhibit viral replication and produce strong antiviral efficacy at a dose 10 times lower than that of TDF. 6 Moreover, TAF administration results in a higher intracellular TFV diphosphate concentration and a 90% reduction in plasma TFV concentration.…”