title: Pharmacokinetics and tolerability of Tenofovir disoproxil fumarate 300 mg once daily: an open-label, single- and multiple-dose study in healthy Chinese subjects.
abstract: 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.
  
  
  OBJECTIVE
  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 t½ was ~21 hours with single dosing. The mean ratio of AUC0-τ 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.
authors.affiliation: Department of Clinical Pharmacology, Zhong Shan Hospital, Fudan University, Shanghai, China; Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
authors.forename: Chao-Ying
authors.initials: CY
authors.lastname: Hu
authors.affiliation: Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Liu
authors.affiliation: Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Clinical Development, GlaxoSmithKline R&D China, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wu
authors.affiliation: Clinical Development, GlaxoSmithKline R&D China, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Dong
authors.affiliation: Clinical Development, GlaxoSmithKline R&D China, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
authors.forename: Jing-Ying
authors.initials: JY
authors.lastname: Jia
authors.affiliation: Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Lu
authors.affiliation: Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
authors.forename: Shi-Xuan
authors.initials: SX
authors.lastname: Sun
authors.affiliation: Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Clinical Pharmacology, Zhong Shan Hospital, Fudan University, Shanghai, China. Electronic address: clab001@126.com.
authors.forename: Xuening
authors.initials: X
authors.lastname: Li
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D044966:Anti-Retroviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D044466:Asian People; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068698:Tenofovir; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine
keywords: LC-MS/MS; pharmacokinetics; tenofovir disoproxil fumarate; tolerability