title: Pregnancy-related effects on tenofovir pharmacokinetics: a population study with 186 women.
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.
authors: Université Paris Descartes Sorbonne Paris Cité, EA3620, Paris, France.
authors: Sihem
authors: S
authors: Benaboud
authors: Déborah
authors: D
authors: Hirt
authors: Odile
authors: O
authors: Launay
authors: Emmanuelle
authors: E
authors: Pannier
authors: Ghislaine
authors: G
authors: Firtion
authors: Elisabeth
authors: E
authors: Rey
authors: Naïm
authors: N
authors: Bouazza
authors: Frantz
authors: F
authors: Foissac
authors: Hélène
authors: H
authors: Chappuy
authors: Saik
authors: S
authors: Urien
authors: Jean Marc
authors: JM
authors: Tréluyer
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D063065:Organophosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011247:Pregnancy / Q000378:metabolism*; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000821:virology; D011262:Pregnancy Trimester, Second / Q000378:metabolism; D011263:Pregnancy Trimester, Third / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000068698:Tenofovir; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine