High Plasma Concentrations of Zidovudine (AZT) Do Not Parallel Intracellular Concentrations of AZT-Triphosphates in Infants during Prevention of Mother-to-Child HIV-1 Transmission

Ei Kinai, Shingo Kato, Shinichi Hosokawa, Miyuki Sadatsuki, Hiroyuki Gatanaga, Yoshimi Kikuchi, Nguyen Van Lam, Do Quan Ha, Nguyen Van Kinh, Nguyen Thanh Liem, Shinichi Oka

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Objectives: Zidovudine (AZT) is mainly used to prevent mother-to-child HIV-1 transmission (PMTCT). Despite serious concerns on AZT-associated toxicity, there is little information on pharmacokinetics of intracellular AZT metabolites in infants. Methods: We conducted a prospective study in 31 HIV-uninfected infants who received AZT for PMTCT. Blood samples were obtained from 14 infants on postdelivery days (PDD) 1, 7, 14, and 28 and from 17 infants at 0 and 4 hours after dosing on PDD-1. Plasma AZT concentrations (pAZT) and intracellular concentrations of AZT-monophosphate (icAZT-MP), diphosphate (icAZT-DP), and triphosphate (icAZT-TP) were determined. Results: Plasma AZT and icAZT-MP concentrations were 2713 nmol/L and 79 fmol/106 cells in PDD-1, but decreased to 1437 nmol/L and 31 fmol/106 cells by PDD-28 (P 0.02 and P 0.07 for all PDDs, respectively), whereas those of icAZT-DP and icAZT-TP remained low throughout the sampling period (P 0.29 and P 0.61 for all PDDs, respectively) There were no differences in icAZT-TP between infants of the 2 mg/kg 4 times a day dose and 4 mg/kg twice daily dose (P 0.25), whereas pAZT and icAZT-MP levels were higher in the latter (P < 0.01 and <0.01, respectively). The pAZT and icAZT-MP significantly increased from 0 to 4 hours after dosing (P < 0.001 and <0.001, respectively), whereas icAZT-DP, icAZT-TP levels were not changed (P 0.41 and 0.33, respectively). Conclusions: The level of icAZT-TP did not change with age, time, or a single dose despite the wide range of pAZT concentration. A safer dosage needs to be determined because high pAZT levels do not parallel those of icAZT-TP.

Original languageEnglish
Pages (from-to)246-253
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume72
Issue number3
DOIs
Publication statusPublished - 2016 Jul 1

Keywords

  • AZT-triphosphates
  • infants
  • intracellular concentration
  • prevention of mother-to-child HIV-1 transmission (PMTCT)
  • zidovudine (AZT)

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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