title: Pharmacokinetics and tolerance of zidovudine in preterm infants.
abstract: OBJECTIVE
  To determine zidovudine pharmacokinetics and tolerance in premature human human immunodeficiency virus-exposed infants.
  
  
  METHODS
  Pediatric AIDS Clinical Trials Group Study 331 was a multicentered prospective, open-label study of the use of zidovudine in premature infants. Thirty-eight infants <35 weeks' gestational age (GA) were studied while receiving zidovudine 1.5 mg/kg every 12 hours until 2 weeks of age, then 2.0 mg/kg every 8 hours until 6 weeks of age. Population pharmacokinetics were evaluated at 1, 2, and 4 weeks' postnatal age; zidovudine doses were adjusted to maintain troughs <3 microM.
  
  
  RESULTS
  Zidovudine clearance was lower than reported in term infants at similar postnatal ages. Nine premature infants required dose reduction because of high levels (7/19 <30 weeks' and 2/19 >/=30 weeks' GA). Postnatal age, GA, serum creatinine, and furosemide use independently predicted zidovudine clearance. Zidovudine was generally well tolerated in this high-risk population.
  
  
  CONCLUSIONS
  Zidovudine clearance is greatly reduced in premature infants. We recommend the following zidovudine dosing schedule in this population: 1.5 mg/kg (intravenous) or 2.0 mg/kg (oral) every 12 hours increased to every 8 hours at 2 weeks of age (>/=30 weeks' GA) or at 4 weeks (<30 weeks' GA).
authors.affiliation: University of California, San Diego, USA. ecapparelli@ucsd.edu
authors.forename: Edmund V
authors.initials: EV
authors.lastname: Capparelli
authors.forename: Mark
authors.initials: M
authors.lastname: Mirochnick
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Dankner
authors.forename: Suzette
authors.initials: S
authors.lastname: Blanchard
authors.forename: Lynne
authors.initials: L
authors.lastname: Mofenson
authors.forename: George D
authors.initials: GD
authors.lastname: McSherry
authors.forename: Hannah
authors.initials: H
authors.lastname: Gay
authors.forename: Gregory
authors.initials: G
authors.lastname: Ciupak
authors.forename: Betsy
authors.initials: B
authors.lastname: Smith
authors.forename: James D
authors.initials: JD
authors.lastname: Connor
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000517:prevention & control* / Q000635:transmission; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D015215:Zidovudine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine