Zidovudine (ZDV) administration to HIV infected mothers during pregnancy and to newborn infants during the first 6 weeks of life significantly reduces vertical HIV transmission. The pharmacokinetics (PK) of ZDV in term newborn infants show reduced elimination due to immature renal and glucuronidation clearances (Boucher et al J Pediatr 1993;122:137). Since these pathways are likely to be even less developed in premature infants, we investigated the pharmacokinetics of ZDV in 7 premature infants. The infants were born at 28 to 33 weeks gestational age (GA) (mean 30.6 weeks) and weighed 710 to 1980 gms(mean 1229 gms). All infants received ZDV intravenously in doses ranging from 1.5 mg/kg q 12 hrs to 2 mg/kg q 6 hrs. None of the infants had evidence of hepatic or renal dysfunction. Two to five samples (mean 3.7 samples) were obtained in each individual at 1-10 days of life (mean 3.4 days). Bayesean estimates of ZDV PK parameters were generated using a one compartment model and NONMEM (posthoc method). Individual PK parameters were used to simulate steady-state ZDV trough concentrations on 1.5 mg/kg q 12 hrs. The mean PK parameters are compared to those observed in term infants:Table Observed peak ZDV levels exceeded 4 uM in the 6 infants receivng ZDV q 12 hrs. ZDV clearance in the 3 infants 30 weeks GA or less (2.7 ml/min/kg) was similar to that seen in the infants greater than 30 weeks GA (2.9 ml/min/kg). Two infants had PK evaluations repeated at 15 days of life and in both ZDV clearance increased with age, but remained less than half the clearance reported in term infants. Conclusions:(1) ZDV clearance is significantly impaired in premature infants resulting in a prolonged half-life and elevated levels from the standard dosage. (2) Reducing the initial ZDV dose in premature infants to 1.5 mg/kg q 12 hrs will maintain ZDV levels > 1 uM and achieve an AUC similar to that observed in term infants on ZDV 2 mg/kg q 6 hrs.

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