Transplacental administration to mice resulted in an increased incidence and multiplicity of lung and liver tumours and in an increased incidence of female reproductive tract tumours in one study, whereas no increased tumour incidence was associated with treatment in another study at a lower dose. After transplacental and postnatal administration of zidovudine to mice, an increased incidence of vaginal squamous-cell carcinomas was seen. The achievement of maximum plasma concentrations and removal from plasma of the parent compound are rapid except in patients with compromised renal function. The pharmacokinetics in nonhuman primates is virtually identical to that in humans. The absorption, distribution and elimination of zidovudine in rodents are more rapid than in humans, and its bioavailability is higher in rats and mice than in primates.
Unchanged zidovudine constitutes up to one-fifth of the human urinary products.
Similar toxic effects are found in treated mice. Zidovudine crosses the placenta by bidirectional passive diffusion, and the drug and its monophosphate and monoglucuronide metabolites were observed in fetal tissue. Studies of children up to 4.2 years of age who had been exposed in utero and for up to six weeks after birth to zidovudine provided no evidence for an increased incidence of structural developmental abnormalities or cognitive or immune dysfunction. Studies in monkeys and rats indicated that the behavioural alterations in offspring exposed to zidovudine in utero were generally reversible. Zidovudine is incorporated into nuclear and mitochondrial DNA in mammalian cells in culture, in experimental animals and in humans.