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Zidovudine pharmacokinetics in premature infants exposed to human immunodeficiency virus
M Mirochnick1, E Capparelli, W Dankner
1Department of Pediatrics, Boston Medical Center, and Boston University School of Medicine, Massachusetts 02118, USA. markm@bu.edu
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Zidovudine (ZDV) has prolonged half-life and low clearance in preterm neonates. Dosing adjustments are crucial to prevent toxic serum concentrations, suggesting reduced initial ZDV doses.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Clinical Pharmacy
Background:
- Zidovudine (ZDV) is an antiretroviral medication used in treating HIV.
- Pharmacokinetic parameters of ZDV in preterm neonates are not well-established.
- Premature infants may have altered drug metabolism and elimination compared to full-term infants.
Purpose of the Study:
- To determine zidovudine (ZDV) pharmacokinetic parameters in preterm neonates.
- To assess the impact of postnatal age on ZDV pharmacokinetics.
- To provide dosing recommendations for ZDV in preterm infants to avoid toxicity.
Main Methods:
- Population pharmacokinetic analysis was employed.
- Data were collected from 15 preterm neonates (mean gestational age 29.4 weeks).
- Seven infants were studied longitudinally to evaluate changes with postnatal age.
Main Results:
- ZDV exhibited low clearance (2.53 ml/min/kg) and a prolonged half-life (7.2 h) in preterm neonates.
- Clearance significantly increased (P=0.024) and half-life decreased (P=0.003) with advancing postnatal age.
- Standard full-term infant dosing may lead to potentially toxic serum concentrations.
Conclusions:
- Preterm neonates have distinct ZDV pharmacokinetics compared to full-term infants.
- ZDV dosing should be individualized based on postnatal age to ensure safety and efficacy.
- A reduced initial ZDV dose of 1.5 mg every 12 hours is suggested for preterm neonates.
Abstract:
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.