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Antimicrobial Agents and Chemotherapy, April 1998, p. 808-812, Vol. 42, No. 4
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Zidovudine Pharmacokinetics in Premature Infants Exposed to Human Immunodeficiency Virus

Mark Mirochnick,1,* Edmund Capparelli,2 Wayne Dankner,2 Rhoda S. Sperling,3 Russ van Dyke,4 and Stephen A. Spector2

Department of Pediatrics, Boston Medical Center, and Boston University School of Medicine, Boston, Massachusetts1; Department of Pediatrics, the University of California at San Diego, La Jolla, California2; Department of Obstetrics, Gynecology and Reproductive Science, Mount Sinai School of Medicine, New York, New York3; and Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana4

Received 3 March 1997/Returned for modification 15 July 1997/Accepted 23 December 1997

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.

* Corresponding author. Mailing address: Boston Medical Center, Maternity 2, One Boston Medical Center Place, Boston, MA 02118. Phone: (617) 534-5461. Fax: (617) 534-7297. E-mail: markm{at}bu.edu.

Antimicrobial Agents and Chemotherapy, April 1998, p. 808-812, Vol. 42, No. 4
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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