title: The pharmacokinetics of zidovudine administered by continuous infusion in children.
abstract: OBJECTIVE
  To define the pharmacokinetics of zidovudine (azidothymidine) in children with human immunodeficiency virus infection.
  
  
  METHODS
  Plasma, urine, and cerebrospinal fluid were obtained following a single 80 mg/m2 body surface dose infused over 1 hour (n = 9), and during a continuous infusion of 0.5 (n = 3), 0.9 (n = 8), 1.4 (n = 7), or 1.8 (n = 3) mg/kg body weight per hour.
  
  
  METHODS
  Outpatient clinic and inpatient ward of the Pediatric Branch of the National Cancer Institute.
  
  
  METHODS
  Twenty-one children (seventeen boys) ranging in age from 14 months to 12 years with symptomatic human immunodeficiency virus infection who were being treated on a phase I-II study of continuous intravenous infusion zidovudine.
  
  
  RESULTS
  Zidovudine disappearance following bolus administration was rapid and biexponential with half-lives of 9.6 and 92 minutes, and a total clearance of 705 +/- 330 mL/min.m2. Zidovudine remained above 1 mumol/L, the optimal virostatic concentration in vitro, for only 1.5 hours. In contrast, with continuous infusion steady-state plasma zidovudine concentrations (Css) were maintained above 1 mumol/L continuously, even at the lowest infusion rate. At steady state the ratio of cerebrospinal fluid zidovudine concentration to plasma was 24% +/- 9%. Patients who developed severe neutropenia (absolute neutrophil count less than 0.5 X 10(9)/L) on the continuous infusion regimen had significantly higher plasma Css. Six of eight had a Css greater than 3.0 mumol/L.
  
  
  CONCLUSIONS
  Pharmacokinetic parameters show that continuous infusion is better than an intermittent schedule in maintaining minimal virostatic concentrations of the drug with a lower daily dose.
authors.affiliation: National Institutes of Health, Bethesda, Maryland.
authors.forename: F M
authors.initials: FM
authors.lastname: Balis
authors.forename: P A
authors.initials: PA
authors.lastname: Pizzo
authors.forename: R F
authors.initials: RF
authors.lastname: Murphy
authors.forename: J
authors.initials: J
authors.lastname: Eddy
authors.forename: P F
authors.initials: PF
authors.lastname: Jarosinski
authors.forename: J
authors.initials: J
authors.lastname: Falloon
authors.forename: S
authors.initials: S
authors.lastname: Broder
authors.forename: D G
authors.initials: DG
authors.lastname: Poplack
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000378:metabolism*; D000367:Age Factors; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D015215:Zidovudine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D015215:Zidovudine