Systemic pharmacokinetics and cellular pharmacology of zidovudine in human immunodeficiency virus type 1-infected women and newborn infants.

  • Rodman J
  • Flynn P
  • Robbins B
 et al. 
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Systemic and intracellular pharmacokinetics of zidovudine were determined for 28 human immunodeficiency virus type 1-infected pregnant women and their newborn infants. Plasma zidovudine and intracellular zidovudine monophosphate and triphosphate concentrations were determined in serial maternal samples and cord blood at delivery. Higher levels of cord blood zidovudine were associated with lower maternal zidovudine clearance and longer infusion times. Median levels of zidovudine monophosphate and triphosphate in maternal (1556 and 67 fmol/106 cells) and cord (1464 and 70 fmol/106 cells) blood were similar but highly variable. Intersubject pharmacokinetic variability for zidovudine is substantial, but intravenous therapy provides plasma concentrations and intracellular zidovudine triphosphate levels consistent with high antiviral activity. The substantial amount of intracellular zidovudine triphosphate in cord blood provides an explanation for the clinical success of zidovudine in reducing vertical transmission. Studies of simpler oral regimens of zidovudine can now be evaluated regarding the ability to achieve these pharmacologic end points associated with highly effective parenteral therapy.

Author-supplied keywords

  • Adolescent
  • Adult
  • Anti-HIV Agents
  • Anti-HIV Agents: blood
  • Anti-HIV Agents: pharmacokinetics
  • Anti-HIV Agents: therapeutic use
  • Dideoxynucleotides
  • Female
  • Fetal Blood
  • Fetal Blood: chemistry
  • Fetal Blood: virology
  • HIV Infections
  • HIV Infections: blood
  • HIV Infections: drug therapy
  • HIV Infections: transmission
  • HIV Infections: virology
  • HIV-1
  • Humans
  • Infant
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical
  • Phosphorylation
  • Pregnancy
  • Pregnancy Complications, Infectious
  • Pregnancy Complications, Infectious: drug therapy
  • Pregnancy Complications, Infectious: virology
  • Reverse Transcriptase Inhibitors
  • Reverse Transcriptase Inhibitors: blood
  • Reverse Transcriptase Inhibitors: pharmacokinetics
  • Reverse Transcriptase Inhibitors: therapeutic use
  • Thymine Nucleotides
  • Thymine Nucleotides: blood
  • Zidovudine
  • Zidovudine: analogs & derivatives
  • Zidovudine: blood
  • Zidovudine: pharmacokinetics
  • Zidovudine: therapeutic use

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  • J H Rodman

  • P M Flynn

  • B Robbins

  • E Jimenez

  • a D Bardeguez

  • J F Rodriguez

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