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

Systemic and intracellular pharmacokinetics of zidovudine were determined f or 28 human immunodeficiency virus type 1-infected pregnant women and their newborn infants. Plasma zidovudine and intracellular zidovudine monophosph ate and triphosphate concentrations were determined in serial maternal samp les and cord blood at delivery. Higher levels of cord blood zidovudine were associated with lower maternal zidovudine clearance and longer infusion ti mes, Median levels of zidovudine monophosphate and triphosphate in maternal (1556 and 67 fmol/10(6) cells) and cord (1464 and 70 fmol/10(6) cells) bloo d were similar but highly variable. Intersubject pharmacokinetic variabilit y for zidovudine is substantial, but intravenous therapy provides plasma co ncentrations and intracellular zidovudine triphosphate levels consistent wi th high antiviral activity, The substantial amount of intracellular zidovud ine triphosphate in cord blood provides an explanation for the clinical suc cess of zidovudine in reducing vertical transmission. Studies of simpler or al regimens of zidovudine can now be evaluated regarding the ability to ach ieve these pharmacologic end points associated with highly effective parent eral therapy.