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Antimicrob Agents Chemother. 2012 Feb;56(2):857-62. doi: 10.1128/AAC.05244-11. Epub 2011 Nov 28.

Pregnancy-related effects on tenofovir pharmacokinetics: a population study with 186 women.

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1
Université Paris Descartes Sorbonne Paris Cité, EA3620, Paris, France.

Abstract

According to the European AIDS Clinical Society, tenofovir disoproxil fumarate can be used in HIV-infected pregnant women if started prior to pregnancy, although no data are available on the pharmacokinetics of tenofovir (TFV) during pregnancy. The aim of this study was to describe TFV pharmacokinetics in HIV-infected women and to evaluate the effect of pregnancy on TFV disposition. Samples were collected according to a therapeutic drug monitoring in 186 women, including 46 pregnant women treated with TFV and retrospectively analyzed by a population approach. TFV pharmacokinetics were ascribed to an open two-compartment model with linear absorption and elimination. The mean population parameter estimates (between-subject variability) were as follows: absorption rate constant, 0.56 h(-1); elimination clearance, 59.9 liters h(-1) (0.436); central volume of distribution, 552 liters (1.96); intercompartmental clearance, 172 liters/h; and peripheral volume of distribution, 1,390 liters. Pregnant women had a 39% higher apparent clearance compared to nonpregnant women. Apparent clearance significantly decreased with age. In order to obtain an exposure similar to the known exposure in adults and guarantee similar trough concentrations (C(min)) as observed in adults, an increase in the TFV dose should be considered for women from the second trimester to delivery.

PMID:
22123690
PMCID:
PMC3264275
DOI:
10.1128/AAC.05244-11
[Indexed for MEDLINE]
Free PMC Article

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