Plasma pharmacokinetics and urinary excretion of tenofovir following cessation in adults with controlled levels of adherence to tenofovir disoproxil fumarate
Plasma pharmacokinetics and urinary excretion of tenofovir following cessation in adults with controlled levels of adherence to tenofovir disoproxil fumarate
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DOI：
10.1016/j.ijid.2020.06.037
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发表时间：
2020-08-01
影响因子：
8.4
通讯作者：
Drain, Paul K.
中科院分区：
文献类型：
--
作者：
Cressey, Tim R.;Siriprakaisil, Oraphan;Drain, Paul K.
目的：目的是充分表征血浆和尿液洗脱替诺福韦酯（TFV）的药代动力学在成人后6周的控制水平的替诺福韦酯富马酸盐（TDF）adherence，以通知实用的临床为基础的坚持testing.Design：这是一个三臂，随机，开放标签的研究在成人志愿者。受试者随机接受TDF 300 mg/恩曲他滨（FTC）200 mg，剂量为（1）7剂/周（完全依从性），（2）4剂/周（中度依从性）或（3）2剂/周（低依从性）。在6周的给药期和停药后4周定期收集血浆和尿液样本。中位（范围）年龄为33（20-49）岁。在洗脱期间，未观察到研究组间TFV药代动力学参数的差异。给药后4 - 10 h，各组间TFV血浆浓度存在微小差异。在给药后24小时，尿液中排泄的TFV累积量无差异，但在148小时，完全、中度和低依从性组分别为24.8 mg、21.0 mg和17.2 mg（p = 0.043）.结论：在具有不同TDF坚持模式的成人中，停药后TFV的血浆浓度和累积尿液提取的相对差异较小。血浆或尿液中的TFV测量值更能指示末次药物摄入，而不是既往剂量模式。(C)2020作者由Elsevier Ltd代表国际传染病学会出版。这是一个在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Objectives: The aim was to fully characterize the plasma and urine washout pharmacokinetics of tenofovir (TFV) in adults following 6 weeks of controlled levels of tenofovir disoproxil fumarate (TDF) adherence, in order to inform the utility of clinic-based adherence testing.Design: This was a three-arm, randomized, open-label study in adult volunteers. Participants were randomized to receive TDF 300 mg/emtricitabine (FTC) 200 mg as (1) 7 doses/week (perfect adherence), (2) 4 doses/week (moderate adherence), or (3) 2 doses/week (low adherence). Plasma and urine samples were collected regularly during the 6-week dosing phase and for 4 weeks following drug cessation.Results: Twenty-eight adults were included in this analysis. Median (range) age was 33 (20-49) years. No differences in TFV pharmacokinetic parameters during the washout were observed across the study arms. Small differences in TFV plasma concentrations occurred across arms between 4 and 10 h post-dose. The cumulative amount of TFV excreted in urine was not different at 24 h post-dose, but at 148 h it was 24.8 mg, 21.0 mg, and 17.2 mg for the perfect, moderate, and low adherence arms, respectively (p = 0.043).Conclusions: Among adults with different TDF adherence patterns, relative differences in plasma concentrations and cumulative urine extraction of TFV were minor following cessation. TFV measurement in plasma or urine is more indicative of last drug ingestion, rather than prior dose patterns. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).