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Pregnancy related effects on Lamivudine Pharmacokinetics: a Population Study with 228 women.
MedLine Citation:
PMID:  22106227     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The aim of this study was to describe lamivudine (3TC) pharmacokinetics (PK) in HIV-infected non pregnant, pregnant women and their fetus. Samples were collected according to a therapeutic drug monitoring in 228 women treated with lamivudine and retrospectively analyzed by a population approach. They were also collected in cord blood and amniotic fluid at birth. Lamivudine pharmacokinetics was ascribed to an open 2- compartment with linear absorption and elimination. Mean population parameter estimates (inter-subject variability) were, for women, absorption rate constant 1.04 h(-1), elimination clearance 23.6 (0.266) L.h(-1) central volume of distribution 109 (0.897) L, intercompartmental clearance 6.7 L/h and peripheral volume of distribution 129 L. A fetal compartment was linked to maternal circulation by mother-to-cord (or fetus) and cord-to-mother rate constants, 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, 0.163 h(-1), and a fixed constant swallowing flow. Placental transfer expressed as fetal-to-maternal AUCs ratio was 0.86 and lamivudine amniotic fluid accumulation expressed as amniotic-fluid-to-fetal AUCs ratio was 2.9. Pregnant women had a 22% higher apparent clearance compared to non pregnant and parturient women, however this increase did not lead to a subexposure and should not require 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:  -     ISSN:  1098-6596     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Université Paris Descartes, EA3620, Paris, France.
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