PHARMACOKINETICS OF ZIDOVUDINE IN CHILDREN WITH SYMPTOMATIC HIV-INFECTION

The pharmacokinetics of zidovudine in 7 haemophiliac children with symptomatic human immunodeficiency virus disease were assessed after administration of oral dosages of 150 and 180 mg/m2 4 times daily separated by at least 2 weeks. The mean duration of zidovudine treatment was 3 months (range 2 to 5 months). The following mean (+/- SD) pharmacokinetic parameters were determined with the lower and higher doses, respectively; maximum plasma zidovudine concentration 6.34 +/- 3.06 vs 7.09 +/- 3.56 mumol/L, terminal half-life 0.84 +/- 0.10 vs 0.94 +/- 0.25 h, and appararent oral clearance 48.8 +/- 5.7 vs 54.2 +/- 11.3 ml/min/kg. Plasma concentrations of the metabolite 3'-azido-3'-deoxy-5'-beta-D-glucopyranosyl thymidine (GZDV) were 2- to 3-fold greater than those of zidovudine, and the terminal portion of the plasma concentration profile of GZDV declined in parallel with that of zidovudine. The pharmacokinetic parameters of zidovudine in these children were very similar to those previously observed in adults. However, there is a suggestion that the apparent oral clearance may be slightly greater in children (present study 49 to 54 ml/min/kg) than in adults (approximately 40 ml/min/kg).