Maternal-fetal transfer and amniotic fluid accumulation of lamivudine in human immunodeficiency virus–infected pregnant women

doi:10.1067/mob.2001.108344

American Journal of Obstetrics and Gynecology

Volume 184, Issue 2, January 2001, Pages 153-158

https://doi.org/10.1067/mob.2001.108344 Get rights and content

Abstract

Objective: The purpose of this study was to investigate placental transfer and amniotic fluid concentrations of lamivudine in human immunodeficiency virus–infected women who received the agent during pregnancy. Study Design: Mothers in the study were receiving antiretroviral therapy that included lamivudine in a clinical setting. Maternal blood, cord blood, and amniotic fluid samples were obtained simultaneously at the time of delivery from 57 mother-infant pairs. Results: At a median of 8.5 hours after the last maternal oral 150-mg dose of lamivudine, median maternal and fetal plasma concentrations were 302 and 240 ng/mL, respectively. Individual maternal and fetal concentrations were strongly correlated (r ² = 0.36; P < 10^–4), and their median ratio was about 1. The median concentration in the amniotic fluid was 5 times higher than that in maternal plasma (upper range of ratio, 133). Conclusion: Lamivudine appeared to cross the placenta by simple diffusion and is concentrated in the amniotic fluid. High amniotic fluid levels of lamivudine may carry both benefits and risks for the child. (Am J Obstet Gynecol 2001;184:153-8.)

Section snippets

Material and methods

A total of 57 mother-infant pairs were included in the study between September 1997 and September 1998. All women were delivered in the Department of Obstetrics of the Cochin–Port Royal Hospital, Paris, and were enrolled with informed consent in the French Perinatal Cohort, as approved by the institutional review board. In addition, 32 women participated in a clinical open-label study of lamivudine with zidovudine for the prevention of mother-to-child HIV transmission (ANRS [Agence Nationale de

Results

The median maternal lamivudine concentration was 302.5 ng/mL at a median of 8.15 hours after the last oral dose of 150 mg (range, 2.3-24.0 hours; Table I).The concentration in maternal plasma decreased in accordance with the time between the last lamivudine dose and sampling. Only 2 values of maternal plasma concentration were undetectable (<25 ng/mL); these were 21 and 24 hours after the last maternal dose, respectively. There was no significant correlation between maternal weight and plasma

Comment

Lamivudine crossed the placenta in HIV-infected pregnant women and was present at high concentrations in the amniotic fluid. The ratio of the concentration in the fetal plasma to that in the maternal plasma was about 1, which suggests that lamivudine freely crossed the placenta through a passive diffusion mechanism and remained essentially intact. Although the maternal plasma concentrations of lamivudine ranged widely from peak to residual therapeutic values, there was no evidence of saturation

Acknowledgements

We thank Sandrine Majoux, Annie Chevallier, and the staff of the Port Royal Maternity for their help in collecting and processing the samples.

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^☆: Supported in part by ANRS (Agence Nationale de Recherches sur le Sida) (EP 13).

^☆☆: Reprint requests: Laurent Mandelbrot, MD, Service de GynécologieObstétrique, Maternité Port Royal, 123 Boulevard de Port Royal, 75014 Paris, France.

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ObstetricsMaternal-fetal transfer and amniotic fluid accumulation of lamivudine in human immunodeficiency virus–infected pregnant women☆,☆☆

Abstract

Section snippets

Material and methods

Results

Comment

Acknowledgements

Am J Obstet Gynecol

J Pediatr

Biochem Pharmacol

J Chromatogr B Biomed Appl

Am J Obstet Gynecol

Am J Med Sci

Am J Obstet Gynecol

Placenta

Am J Obstet Gynecol

Am J Obstet Gynecol

Eur J Obstet Gynecol Reprod Biol

Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment

N Engl J Med

Obstetrics
Maternal-fetal transfer and amniotic fluid accumulation of lamivudine in human immunodeficiency virus–infected pregnant women☆,☆☆