title: Pregnancy-related effects on lamivudine pharmacokinetics in a population study with 228 women.
abstract: The aim of this study was to describe lamivudine (3TC) pharmacokinetics (PK) in HIV-infected nonpregnant and pregnant women and their fetuses. Samples were collected according to therapeutic drug monitoring from 228 women treated with lamivudine and retrospectively analyzed by a population approach. The samples were also collected from cord blood and amniotic fluid at birth. Lamivudine pharmacokinetics were ascribed to an open two-compartment model with linear absorption and elimination. Mean population parameter estimates (intersubject variability) for women were an absorption rate constant of 1.04 h(-1), an elimination clearance rate of 23.6 (0.266) liters · h(-1), a central volume of distribution of 109 (0.897) liters, an intercompartmental clearance rate of 6.7 liters/h, and a peripheral volume of distribution of 129 liters. A fetal compartment was linked to maternal circulation by mother-to-cord (or fetus) and cord-to-mother rate constants of 0.463 h(-1) and 0.538 h(-1), respectively. The amniotic fluid compartment was connected to the fetal compartment with an elimination rate constant of 0.163 h(-1) and a fixed-constant swallowing flow. The placental transfer expressed as fetal-to-maternal area under the concentration-time curve (AUC) ratio was 0.86, and the lamivudine amniotic fluid accumulation, expressed as the amniotic fluid-to-fetal AUC ratio, was 2.9. Pregnant women had a 22% higher apparent clearance than nonpregnant and parturient women; however, this increase did not lead to subexposure and should not require a dosage adjustment.
authors: Université Paris Descartes, Paris, France. nedjma.benaboud@parisdescartes.fr
authors: Sihem
authors: S
authors: Benaboud
authors: Jean Marc
authors: JM
authors: Tréluyer
authors: Saik
authors: S
authors: Urien
authors: Stéphane
authors: S
authors: Blanche
authors: Naim
authors: N
authors: Bouazza
authors: Hélène
authors: H
authors: Chappuy
authors: Elisabeth
authors: E
authors: Rey
authors: Emmanuelle
authors: E
authors: Pannier
authors: Ghislaine
authors: G
authors: Firtion
authors: Odile
authors: O
authors: Launay
authors: Déborah
authors: D
authors: Hirt
mesh_terms: D000293:Adolescent; D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016903:Drug Monitoring; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000821:virology; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine