Document Detail


Pregnancy-related effects on lamivudine pharmacokinetics in a population study with 228 women.
MedLine Citation:
PMID:  22106227     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Sihem Benaboud; Jean Marc Tréluyer; Saik Urien; Stéphane Blanche; Naim Bouazza; Hélène Chappuy; Elisabeth Rey; Emmanuelle Pannier; Ghislaine Firtion; Odile Launay; Déborah Hirt
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Publication Detail:
Type:  Journal Article     Date:  2011-11-21
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  56     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-23     Completed Date:  2012-05-25     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  776-82     Citation Subset:  IM    
Affiliation:
Université Paris Descartes, Paris, France. nedjma.benaboud@parisdescartes.fr
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Amniotic Fluid / metabolism
Anti-HIV Agents / administration & dosage,  pharmacokinetics*
Area Under Curve
Drug Monitoring
Female
Fetal Blood / metabolism
HIV Infections / drug therapy*,  virology
Humans
Lamivudine / administration & dosage,  pharmacokinetics*
Maternal-Fetal Exchange / drug effects
Metabolic Clearance Rate
Models, Biological
Pregnancy
Pregnancy Complications, Infectious / drug therapy*,  virology
Reverse Transcriptase Inhibitors / pharmacokinetics*
Young Adult
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Reverse Transcriptase Inhibitors; 134678-17-4/Lamivudine
Comments/Corrections

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