Philip A. Pizzo, M.D.

Publication Details

  • THE PHARMACOKINETICS OF ZIDOVUDINE ADMINISTERED BY CONTINUOUS INFUSION IN CHILDREN ANNALS OF INTERNAL MEDICINE BALIS, F. M., Pizzo, P. A., Murphy, R. F., Eddy, J., Jarosinski, P. F., Falloon, J., Broder, S., POPLACK, D. G. 1989; 110 (4): 279-285

    Abstract:

    To define the pharmacokinetics of zidovudine (azidothymidine) in children with human immunodeficiency virus infection.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.Outpatient clinic and inpatient ward of the Pediatric Branch of the National Cancer Institute.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.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.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.

    View details for Web of Science ID A1989T348800006

    View details for PubMedID 2643914

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