STUDY OBJECTIVE: To define the pharmacokinetics of zidovudine (azidothymidine) in children with human immunodeficiency virus infection. DESIGN: 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. SETTING: Outpatient clinic and inpatient ward of the Pediatric Branch of the National Cancer Institute. PATIENTS: 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. MEASUREMENTS AND MAIN 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.
STUDY OBJECTIVE: To define the pharmacokinetics of zidovudine (azidothymidine) in children with human immunodeficiency virus infection. DESIGN: 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. SETTING:Outpatient clinic and inpatient ward of the Pediatric Branch of the National Cancer Institute. PATIENTS: 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. MEASUREMENTS AND MAIN 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: D P Callender; N Jayaprakash; A Bell; V Petraitis; R Petraitiene; M Candelario; R Schaufele; J M Dunn; S Sei; T J Walsh; F M Balis; R Petratienes Journal: Antimicrob Agents Chemother Date: 1999-04 Impact factor: 5.191
Authors: U Wintergerst; B Rolinski; M Vocks-Hauck; V Wahn; K M Debatin; G Notheis; I Grosch-Wörner; F D Goebel; A A Roscher; B H Belohradsky Journal: Infection Date: 1995 Nov-Dec Impact factor: 3.553
Authors: M Mirochnick; E Capparelli; W Dankner; R S Sperling; R van Dyke; S A Spector Journal: Antimicrob Agents Chemother Date: 1998-04 Impact factor: 5.191