Chao-Ying Hu1, Yan-Mei Liu2, Yun Liu2, Qian Chen2, Wei Wang2, Kai Wu3, Jie Dong3, Jie Li3, Jing-Ying Jia2, Chuan Lu2, Shi-Xuan Sun2, Chen Yu2, Xuening Li4. 1. Department of Clinical Pharmacology, Zhong Shan Hospital, Fudan University, Shanghai, China; Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China. 2. Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China. 3. Clinical Development, GlaxoSmithKline R&D China, Shanghai, China. 4. Department of Clinical Pharmacology, Zhong Shan Hospital, Fudan University, Shanghai, China. Electronic address: clab001@126.com.
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. 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 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. Crown
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 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. Crown
Authors: Yanhui Lu; Vineet Goti; Ayyappa Chaturvedula; Jessica E Haberer; Michael J Fossler; Mark E Sale; David Bangsberg; Jared M Baeten; Connie L Celum; Craig W Hendrix Journal: Antimicrob Agents Chemother Date: 2016-08-22 Impact factor: 5.191
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