PHARMACOKINETIC DISPOSITION OF ZIDOVUDINE DURING PREGNANCY

Zidovudine pharmacokinetics was determined in three human immunodeficiency virus type 1-seropositive women receiving zidovudine (200 mg orally every 4 h) from 19 to 39 weeks of pregnancy and postpartum. Zidovudine concentrations were measured using high-pressure liquid chromatography, and pharmacokinetic analyses were done using model-independent methods. For the pregnant versus postpartum periods, peak zidovudine levels (mean +/- 1 SD) were 3.9 +/- 1.7-mu-mol/l versus 4.3 +/- 0.04-mu-mol/l (P = .56); elimination half-lives were 1.3 +/- 0.6 versus 1.0 +/- 0.3 h (P = .41); areas under the concentration curve were 4.5 +/- 1.0-mu-mol/l x h and 6.8 +/- 0.5-mu-mol/l x h (P = .02); apparent total body clearances were 2.5 +/- 0.6 l/h/kg and 1.7 +/- 0.41/h/kg (P = .05); and apparent steady state volumes of distribution were 3.9 +/- 1.0 l/kg and 2.6 +/- 0.8 l/kg (P = .07), respectively. Umbilical cord serum levels ranged from 113%-127% of maternal levels. No persistent adverse effects of zidovudine therapy were seen in the three women or their babies.