Zidovudine pharmacokinetics in premature infants exposed to human immunodeficiency virus.
We used population analysis techniques to determine zidovudine (ZDV) pharmacokinetic parameters in 15 preterm neonates (mean gestational age, 29.4 weeks; mean birth weight, 1,230 g) at a mean age of 5.5 days. The values of the pharmacokinetic parameters were as follows: clearance, 2.53 +/- 0.44 ml/min/kg; volume of distribution, 1.59 +/- 0.51 liters/kg; and half-life, 7.2 +/- 1.5 h. For seven infants studied a second time, at a mean age of 17.7 days, an increase in the mean clearance (2.33 versus 4.35 ml/min/kg; P = 0.024) and a decrease in the half-life (7.3 versus 4.4 h; P = 0.003) were found. The ZDV clearance is low and the half-life is prolonged in premature neonates, but the clearance increases and the half-life decreases with postnatal age. Potentially toxic concentrations may accumulate in serum if the standard dosage for full-term infants is used. We suggest that initial ZDV dosing should be reduced to 1.5 mg every 12 h for preterm neonates.
Mirochnick
M
M
Department of Pediatrics, Boston Medical Center, and Boston University School of Medicine, Massachusetts 02118, USA. markm@bu.edu
Capparelli
E
E
Dankner
W
W
Sperling
R S
RS
van Dyke
R
R
Spector
S A
SA
D000375:Aging / Q000378:metabolism; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D005260:Female; D005865:Gestational Age; D015658:HIV Infections / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D008297:Male; D015215:Zidovudine / Q000493:pharmacokinetics*
D000998:Antiviral Agents; D015215:Zidovudine