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Antimicrobial Agents and Chemotherapy, March 2009, p. 1067-1073, Vol. 53, No. 3
0066-4804/09/$08.00+0 doi:10.1128/AAC.00860-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Population Pharmacokinetics of Emtricitabine in Human Immunodeficiency Virus Type 1-Infected Pregnant Women and Their Neonates
Déborah Hirt,1,2*
Saik Urien,1,2
Elisabeth Rey,3
Elise Arrivé,4
Didier K. Ekouévi,5
Patrick Coffié,5
Sim Kruy Leang,6
Sarita Lalsab,7
Divine Avit,5
Eric Nerrienet,8
James McIntyre,7
Stéphane Blanche,9
François Dabis,4 and
Jean-Marc Tréluyer1,2,3
EA3620, Université Paris—Descartes, Paris, France,1 Unité de Recherche Clinique, AP-HP, Hôpital Tarnier, Paris, France,2 Service de Pharmacologie Clinique, AP-HP, Hôpital Cochin-Saint-Vincent-de-Paul, Université Paris—Descartes, Paris, France,3 INSERM U897, ISPED, Université Victor Segalen, Bordeaux, France,4 Programme PAC-CI, ANRS Abidjan, Côte d'Ivoire,5 Service Gynécologie-Obstétrique de l'Hôpital Calmette, Phnom Penh, Cambodia,6 Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Chris Hani Baragwanath Hospital, Johannesburg, South Africa,7 Institut Pasteur du Cambodge, Phnom Penh, Cambodia,8 Service d'Immunologie et Hématologie Pédiatrique, Hôpital Necker Enfants Malades, Université Paris—Descartes, Paris, France9
Received 28 June 2008/ Returned for modification 28 September 2008/ Accepted 12 December 2008
The objectives of this study were to evaluate emtricitabine (FTC) pharmacokinetics in pregnant women and their neonates and to determine the optimal prophylactic dose for neonates after birth to prevent mother-to-child transmission of human immunodeficiency virus (HIV). A total of 38 HIV-infected pregnant women were administered tenofovir disoproxyl fumarate (300 mg)-FTC (200 mg) tablets—two tablets at the initiation of labor and one daily for 7 days postpartum. By pair, 11 maternal, one cord blood, and two neonatal FTC concentrations were measured using a high-performance liquid chromatography-tandem mass spectrometry validated method and analyzed by a population approach. Model and mean estimates (interpatient variability) were a two-compartment model for mothers, with an absorption rate constant of 0.54 h–1 (61%), apparent elimination and intercompartmental clearances of 23.2 (17%) and 6.04 liters·h–1, and apparent central and peripheral volumes of 127 and 237 liters, respectively; an effect compartment linked to maternal circulation for cord blood and a neonatal compartment disconnected, after delivery, with a 10.6-h half-life (30%). After the 400-mg FTC administration, the median population area under the concentration-time curve and the minimal and maximal plasma FTC concentrations in pregnant women were 14.3 mg·liter–1·h and 1.68 and 0.076 mg/liter, respectively. At delivery, median (range) predicted maternal and cord blood FTC concentrations were, respectively, 1.16 (0.14 to 1.99) and 0.72 (0.05 to 1.19) mg·liter–1. We concluded that the 400-mg FTC administration in pregnant women produces higher exposition than does the 200-mg administration in other adults, at steady state. FTC was shown to have good placental transfer (80%). Administering 1 mg FTC/kg as soon as possible after birth or 2 mg/kg 12 h after birth should produce neonatal concentrations comparable to the concentrations observed in adults.
* Corresponding author. Mailing address: Unité de Recherche Clinique, Hôpital Tarnier, 89 Rue d'Assas, 75006 Paris, France. Phone: 33158412884. Fax: 33158411183. E-mail: deborah.hirt{at}univ-paris5.fr
Published ahead of print on 22 December 2008.
Antimicrobial Agents and Chemotherapy, March 2009, p. 1067-1073, Vol. 53, No. 3
0066-4804/09/$08.00+0 doi:10.1128/AAC.00860-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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