PMID- 24148552
OWN - NLM
STAT- MEDLINE
DCOM- 20140715
LR  - 20221207
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 35
IP  - 12
DP  - 2013 Dec
TI  - Pharmacokinetics and tolerability of Tenofovir disoproxil fumarate 300 mg once 
      daily: an open-label, single- and multiple-dose study in healthy Chinese 
      subjects.
PG  - 1884-9
LID - S0149-2918(13)00971-5 [pii]
LID - 10.1016/j.clinthera.2013.09.020 [doi]
AB  - 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 t(1/2) was ~21 hours 
      with single dosing. The mean ratio of AUC0-tau 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.
CI  - Crown Copyright (c) 2013 Published by Elsevier HS Journals, Inc. All rights 
      reserved.
FAU - Hu, Chao-Ying
AU  - Hu CY
AD  - Department of Clinical Pharmacology, Zhong Shan Hospital, Fudan University, 
      Shanghai, China; Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, 
      Shanghai, China.
FAU - Liu, Yan-Mei
AU  - Liu YM
AD  - Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
FAU - Liu, Yun
AU  - Liu Y
AD  - Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
FAU - Chen, Qian
AU  - Chen Q
AD  - Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
FAU - Wang, Wei
AU  - Wang W
AD  - Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
FAU - Wu, Kai
AU  - Wu K
AD  - Clinical Development, GlaxoSmithKline R&D China, Shanghai, China.
FAU - Dong, Jie
AU  - Dong J
AD  - Clinical Development, GlaxoSmithKline R&D China, Shanghai, China.
FAU - Li, Jie
AU  - Li J
AD  - Clinical Development, GlaxoSmithKline R&D China, Shanghai, China.
FAU - Jia, Jing-Ying
AU  - Jia JY
AD  - Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
FAU - Lu, Chuan
AU  - Lu C
AD  - Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
FAU - Sun, Shi-Xuan
AU  - Sun SX
AD  - Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
FAU - Yu, Chen
AU  - Yu C
AD  - Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
FAU - Li, Xuening
AU  - Li X
AD  - Department of Clinical Pharmacology, Zhong Shan Hospital, Fudan University, 
      Shanghai, China. Electronic address: clab001@126.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT01480622
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131019
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Anti-Retroviral Agents)
RN  - 0 (Organophosphonates)
RN  - 99YXE507IL (Tenofovir)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - Adenine/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics
MH  - Administration, Oral
MH  - Adult
MH  - Anti-Retroviral Agents/*pharmacokinetics/*therapeutic use
MH  - Asian People
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Organophosphonates/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Tenofovir
MH  - Young Adult
OTO - NOTNLM
OT  - LC-MS/MS
OT  - pharmacokinetics
OT  - tenofovir disoproxil fumarate
OT  - tolerability
EDAT- 2013/10/24 06:00
MHDA- 2014/07/16 06:00
CRDT- 2013/10/24 06:00
PHST- 2013/03/25 00:00 [received]
PHST- 2013/09/09 00:00 [revised]
PHST- 2013/09/24 00:00 [accepted]
PHST- 2013/10/24 06:00 [entrez]
PHST- 2013/10/24 06:00 [pubmed]
PHST- 2014/07/16 06:00 [medline]
AID - S0149-2918(13)00971-5 [pii]
AID - 10.1016/j.clinthera.2013.09.020 [doi]
PST - ppublish
SO  - Clin Ther. 2013 Dec;35(12):1884-9. doi: 10.1016/j.clinthera.2013.09.020. Epub 
      2013 Oct 19.