Pharmacokinetics and Tolerability of Tenofovir Disoproxil Fumarate 300 mg Once Daily: An Open-Label, Single- and Multiple-Dose Study in Healthy Chinese Subjects

摘要

Background: Tenofovir disoproxil fumarate (TDF) has been approved worldwide for the treatment of adults with chronic hepatitis B and, in combination with other antiretroviral agents, HIV-1 infection. Although its use for the treatment of HIV has been approved by the Chinese State Food and Drug Administration, there are no data on the pharmacokinetic profile of TDF in Chinese individuals. Objectives: This study aimed to investigate the pharmacokinetic properties and tolerability of TDF in healthy Chinese subjects. Methods: This open-label, single- and multiple-dose study was conducted in healthy Chinese volunteers. Subjects received TDF 300 mg once daily, administered as a single dose (day 1) and multiple doses (days 4-10). Multiple plasma samples were collected over time, and the concentrations of TDF were determined using LC-MS/MS. Pharmacokinetic parameters were estimated using a noncompartmental model. Tolerability was determined using clinical evaluation and monitoring of adverse events (AEs). Results: Fourteen volunteers were enrolled (7 men, 7 women; mean age, 24.6 years). TDF was rapidly absorbed; median Tmax was 0.75 hour, and t1/2 was ~21 hours with single dosing. The mean ratio of AUC0-? steady state/AUC0-24 single dose was 1.55. The pharmacokinetic properties of TDF were consistent between the single dose and multiple doses, and between men and women. No serious AEs were reported, and there were no discontinuations due to AEs. Conclusions: There was an accumulation of approximately 55% in tenofovir exposure in healthy Chinese between multiple dose and single dose. TDF exhibited a pharmacokinetic profile similar to that of healthy Western subjects in a historical comparison. TDF was generally well tolerated in these healthy Chinese subjects. ClinicalTrials.gov identifier: NCT01480622.