Document Detail


Tenofovir, emtricitabine intracellular and plasma, and efavirenz plasma concentration decay following drug intake cessation: implications for HIV treatment and prevention.
MedLine Citation:
PMID:  23274933     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: In vivo data on tenofovir (TFV), emtricitabine (FTC), and efavirenz (EFV) concentration decay after intake cessation are limited; determinations of "true" elimination half-lives (t½) have often been based on suboptimal sampling windows. Understanding these parameters is important in managing missed doses and planning HIV pre-exposure prophylaxis (PrEP). This study investigated the pharmacokinetics (PK) of plasma TFV/FTC, their intracellular (IC) anabolites, TFV-diphosphate (DP) and FTC-triphosphate (TP), and plasma EFV over 10 days after intake cessation in HIV-negative volunteers.
METHODS: Volunteers received an Atripla (TFV/FTV/EFV) tablet daily for 14 days. PK sampling occurred before final dose and up to 228 hours after stopping. Peripheral blood mononuclear cells for [IC](drug) and [plasma](drug) were isolated, with analysis by tandem mass spectrometry.
RESULTS: Sixteen participants completed the study. Geometric mean plasma (t½)(228h) of TFV and FTC were 31 and 37 hours. These were longer than the previous reports (TFV 12-18 hours, FTC 10 hours).Geometric mean (t½)(228h) of IC TFV-DP and FTC-TP were 164 and 39 hours, whereas for EFV in plasma was 92 hours. [EFV](plasma) in 5/16 participants were below the suggested MEC of 1000 ng/mL within 48 hours postdose; however, 50% of the participants maintained concentrations above this level after 84 hours.
CONCLUSIONS: These data fully characterize the PK of TFV and TFV-DP, FTC and FTC-TP, and EFV after stopping the drug combination. Although decay in concentrations can be related to a target for EFV, this is more difficult for the IC phosphates. Consensus on 'target' triphosphate/diphosphate concentrations will further our understanding of missed/delayed doses in treatment and prevention strategies.
Authors:
Akil Jackson; Graeme Moyle; Victoria Watson; John Tjia; Alieu Ammara; David Back; Malika Mohabeer; Brian Gazzard; Marta Boffito
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of acquired immune deficiency syndromes (1999)     Volume:  62     ISSN:  1944-7884     ISO Abbreviation:  J. Acquir. Immune Defic. Syndr.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-08-08     Completed Date:  2013-08-20     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  100892005     Medline TA:  J Acquir Immune Defic Syndr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  275-81     Citation Subset:  IM; X    
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MeSH Terms
Descriptor/Qualifier:
Adenine / administration & dosage,  analogs & derivatives*,  blood,  pharmacokinetics
Adult
Anti-HIV Agents / administration & dosage,  blood,  pharmacokinetics*
Benzoxazines / administration & dosage,  blood,  pharmacokinetics*
Deoxycytidine / administration & dosage,  analogs & derivatives*,  blood,  pharmacokinetics
Drug Combinations
Female
HIV Infections / drug therapy*,  prevention & control
Half-Life
Humans
Leukocytes, Mononuclear / metabolism
Male
Middle Aged
Organophosphonates / administration & dosage,  blood,  pharmacokinetics*
Tandem Mass Spectrometry
Young Adult
Grant Support
ID/Acronym/Agency:
BRF-2011-029//Department of Health
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Benzoxazines; 0/Drug Combinations; 0/Organophosphonates; 0/emtricitabine; 0W860991D6/Deoxycytidine; 107021-12-5/tenofovir; JAC85A2161/Adenine; JE6H2O27P8/efavirenz

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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