823 PHARMACOKINETICS OF VINCRISTINE IN CHILDREN WITH CANCER

Abstract

The pharmacokinetics of vincristine sulfate (VCR) have not been studied in children. Using a radioimmunoassay, VCR concentrations of serum and urine were measured in 4 children with malignancies (ages 5 to 16). Serum samples were obtained from 1 min. to 48 hrs. following intravenous bolus injections of VCR (2mg./M², maximum dose 2.0mg.). Urine samples were obtained up to 90 hrs. following the injection of VCR. The pharmacokinetic data were analyzed by a non-linear regression program, NONLIN. A three compartmental open model fits the raw data better than a two compartmental model. The half-lives of the triphasic decay curves α, β, and γ were 2.4, 27.3, and 1620.0 min., respectively. The mean volume of distribution was 251.85 liters. First order rate constants (min⁻¹) for distribution and/or elimination of VCR were K₁₀=0.038, K₁₂=0.133, K₂₁=0.044, K₁₃=0.119, K₃₁=0.003. The total body clearance was 140.43 ml/min/1.73M² while the ACU: was 28,588 (nM·min). Urinary excretion demonstrated a concentration of > 1.0 × 10⁻⁷M in the urine up to 78 hrs. following the injection. Up to 37% of the administered drug could be recovered in the urine by 90 hrs. The low elimination constant (K₃₁) from poorly perfused tissues to plasma and a long biological half-life (27 hrs.) indicate a slow release of VCR from the body and may account for the neurotoxicity associated with this drug. (Supported in part by NIH grant CA 12197).

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