Pharmacokinetics of zidovudine (azidothymidine). II. Development of metabolic and renal clearance pathways in the neonate

Infection of children with the human immunodeficiency virus, which causes AIDS, results in damage to the nervous system. Improvement of neurologic performance has been observed in children with AIDS who are older than 14 months when zidovudine (ZDV, azidothymidine) is given as a constant infusion. Administration of zidovudine at an earlier age may be more beneficial, and use of the drug in neonates (newborns) is being considered. Before this can be done, the pharmacokinetics (the actions of the drug within the body) must be studied. It must be known whether the pharmacokinetics of ZDV in neonates are similar to the drug's actions in adults. In adults, ZDV can cause problems in the bone marrow due to toxicity, and the toxicity is dependent on the dose and concentration of ZDV given. Therefore, the dose of ZDV may have to be adjusted according to the age of the patient. Changes in the pharmacokinetics of ZDV with age were studied in macaque monkeys ranging in age from newborn to four months old. The pharmacokinetics of ZDV in adult macaques are similar to those in adult humans. The clearance of ZDV from the blood, clearance from the kidneys, and metabolic clearance of ZDV to the glucuronide ZDVG were found to be significantly smaller during the first week of life than at four months of age. It is thought that the reason for this poor clearance is that the neonates' kidneys cannot metabolize (break down) the drug. However, the amount of the drug broken down at four months was similar to the amount metabolized in adults. This indicates that the clearance pathways of ZDV develop quickly, within four months of birth. If ZDV is administered to human neonates, the levels of the drug must be monitored so that the dose may be adjusted for the patient's age. (Consumer Summary produced by Reliance Medical Information, Inc.)