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Antimicrobial Agents and Chemotherapy, July 2008, p. 2555-2563, Vol. 52, No. 7
0066-4804/08/$08.00+0 doi:10.1128/AAC.01130-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
High Levels of Zidovudine (AZT) and Its Intracellular Phosphate Metabolites in AZT- and AZT-Lamivudine-Treated Newborns of Human Immunodeficiency Virus-Infected Mothers
Lucie Durand-Gasselin,1
Alain Pruvost,1
Axelle Dehée,2
Genevieve Vaudre,3
Marie-Dominique Tabone,3
Jacques Grassi,4
Guy Leverger,3
Antoine Garbarg-Chenon,2
Henri Bénech,1* and
Catherine Dollfus3
CEA, iBiTecS, Service de Pharmacologie et d'Immunoanalyse, Gif sur Yvette F-91191, France,1 AP-HP, Hôpital Armand Trousseau, Service de Virologie, Paris F-75012, France, and Université Pierre et Marie Curie-Paris 6, EA 3500, Paris F-75012, France,2 AP-HP, Hôpital Armand Trousseau, Service d'Hématologie et d'Oncologie Pédiatrique, Paris F-75012, France,3 CEA, Direction des Sciences du Vivant, CEA/Saclay, 91191 Gif-sur-Yvette Cedex, France4
Received 27 August 2007/ Returned for modification 5 October 2007/ Accepted 11 April 2008
Newborns from human immunodeficiency virus-infected mothers are given antiretroviral prophylaxis against mother-to-child transmission, including predominantly nucleoside reverse transcriptase inhibitors. Pharmacological monitoring of these drugs in newborns has so far been limited to plasma and cord blood. In this study, samples from newborns (up to 45 days old) treated with zidovudine (AZT) alone (n = 29) or in combination with lamivudine (3TC) (n = 20) were analyzed for both intracellular concentrations of phosphate metabolites in peripheral blood mononuclear cells and levels of parent drugs in plasma. Plasma AZT and intracellular AZT-monophosphate and AZT-triphosphate (TP) concentrations were significantly higher during the first 15 days of life (199 versus 52.7 ng/ml [P < 0.0001], 732 versus 282 fmol/106 cells [P < 0.0001], and 170 versus 65.1 fmol/106 cells [P < 0.0001], respectively) and then became comparable to those of adults. No difference in intracellular AZT metabolite concentrations was found when AZT- and AZT-3TC-treated groups were compared. Plasma 3TC levels (lower limit of quantification [LLOQ], 1,157 ng/ml; median, 412.5 ng/ml) were not associated with the newborn's age, gender, or weight. Intracellular 3TC-TP concentrations (LLOQ, 40.4 pmol/106 cells; median, 18.9 pmol/106 cells) determined for newborns receiving the AZT-3TC combination were associated with neither the age nor weight of the newborns. Concentrations in females were significantly higher (1.8-fold [P = 0.0415]) than those in males. Unexpectedly, newborns on AZT monotherapy whose mothers' treatment included 3TC displayed residual plasma 3TC and intracellular 3TC-TP levels up to 1 week after birth.
* Corresponding author. Mailing address: Service de Pharmacologie et d'Immunoanalyse, CEA, iBiTecS, 91191 Gif-Sur-Yvette Cedex, France. Phone: 33 (0)1 69 08 72 98. Fax: 33 (0)1 69 08 59 07. E-mail: henri.benech{at}cea.fr
Published ahead of print on 21 April 2008.
Antimicrobial Agents and Chemotherapy, July 2008, p. 2555-2563, Vol. 52, No. 7
0066-4804/08/$08.00+0 doi:10.1128/AAC.01130-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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