| Pregnancy-related effects on lamivudine pharmacokinetics in a population study with 228 women. | |
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MedLine Citation:
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PMID: 22106227 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article Date: 2011-11-21 |
Journal Detail:
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Title: Antimicrobial agents and chemotherapy Volume: 56 ISSN: 1098-6596 ISO Abbreviation: Antimicrob. Agents Chemother. Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-01-23 Completed Date: 2012-05-25 Revised Date: 2012-09-25 |
Medline Journal Info:
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Nlm Unique ID: 0315061 Medline TA: Antimicrob Agents Chemother Country: United States |
Other Details:
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Languages: eng Pagination: 776-82 Citation Subset: IM |
Affiliation:
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Université Paris Descartes, Paris, France. nedjma.benaboud@parisdescartes.fr |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/Anti-HIV Agents; 0/Reverse Transcriptase Inhibitors; 134678-17-4/Lamivudine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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