High levels of zidovudine (AZT) and its intracellular phosphate metabolites in AZT- and AZT-lamivudine-treated newborns of human immunodeficiency virus-infected mothers.
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/10(6) cells [P < 0.0001], and 170 versus 65.1 fmol/10(6) 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/10(6) cells; median, 18.9 pmol/10(6) 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.
Durand-Gasselin
Lucie
L
Service de Pharmacologie et d'Immunoanalyse, CEA, iBiTecS, 91191 Gif-Sur-Yvette Cedex, France.
Pruvost
Alain
A
Dehée
Axelle
A
Vaudre
Genevieve
G
Tabone
Marie-Dominique
MD
Grassi
Jacques
J
Leverger
Guy
G
Garbarg-Chenon
Antoine
A
Bénech
Henri
H
Dollfus
Catherine
C
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use*; D054306:Dideoxynucleotides / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011446:Prospective Studies; D013942:Thymine Nucleotides / Q000097:blood; D015215:Zidovudine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood* / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D054306:Dideoxynucleotides; D013942:Thymine Nucleotides; C057287:3'-azido-3'-deoxythymidine 5'phosphate; D019259:Lamivudine; D015215:Zidovudine; C052873:zidovudine triphosphate