Plasma Tenofovir, Emtricitabine, and Rilpivirine and Intracellular Tenofovir Diphosphate and Emtricitabine Triphosphate Pharmacokinetics following Drug Intake Cessation



Dickinson, Laura ORCID: 0000-0001-5557-9396, Yapa, H Manisha, Jackson, Akil ORCID: 0000-0002-4574-544X, Moyle, Graeme, Else, Laura, Amara, Alieu ORCID: 0000-0002-1137-2948, Khoo, Saye ORCID: 0000-0002-2769-0967, Back, David, Karolia, Zeenat, Higgs, Chris
et al (show 1 more authors) (2015) Plasma Tenofovir, Emtricitabine, and Rilpivirine and Intracellular Tenofovir Diphosphate and Emtricitabine Triphosphate Pharmacokinetics following Drug Intake Cessation. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 59 (10). pp. 6080-6086.

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Abstract

Pharmacokinetic (PK) data describing a prolonged time course of antiretrovirals in plasma and peripheral blood mononuclear cells (PBMCs) are important for understanding and managing late or missed doses and to assess the appropriateness of compounds for preexposure prophylaxis (PrEP). This study aimed to evaluate the PK of coformulated tenofovir disoproxil fumarate (DF), emtricitabine, and rilpivirine in plasma and of the intracellular (IC) anabolites tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) in healthy volunteers up to 9 days after drug cessation. Individuals received daily tenofovir DF-emtricitabine-rilpivirine (245/200/25 mg) for 14 days. Drug intake was stopped, and serial sampling occurred prior to the final dose and up to 216 h (9 days) after stopping drug intake. Concentrations were quantified and PK parameters calculated. Eighteen volunteers completed the study. The terminal elimination plasma half-lives for tenofovir and emtricitabine over 216 h (geometric mean [90% confidence interval]) were higher than those seen over 0 to 24 h (for tenofovir, 31 h [27 to 40 h] versus 13.3 h [12.5 to 15.1 h]; for emtricitabine, 41 h [36 to 54 h] versus 6.4 h (5.9 to 7.6 h]). Model-predicted IC half-lives (0 to 168 h) were 116 h (TFV-DP) and 37 h (FTC-TP). The plasma rilpivirine concentration at 216 h was 4.5 ng/ml (4.2 to 6.2 ng/ml), and half-lives over 0 to 216 h and 0 to 24 h were 47 h (41 to 59 h) and 35 h (28 to 46 h), respectively. These data contribute to our understanding of drug behavior following treatment interruption; however, adherence to therapy should be promoted. Validated plasma and IC target concentrations are necessary to allow interpretation with respect to sustained virus suppression or HIV prevention. (The trial was conducted in accordance with the Declaration of Helsinki [EudraCT 2012-002781-13].).

Item Type: Article
Uncontrolled Keywords: Humans, HIV Infections, Adenine, Anti-HIV Agents, Adolescent, Adult, Aged, Middle Aged, Female, Young Adult, Organophosphates, Tenofovir, Emtricitabine, Rilpivirine
Depositing User: Symplectic Admin
Date Deposited: 13 Jul 2018 15:04
Last Modified: 19 Jan 2023 01:30
DOI: 10.1128/AAC.01441-15
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3023731