Pharmacokinetics of vincristine sulfate in children

Summary

A radioimmunoassay was used to measure vincristine sulfate concentrations in the serum of four children with malignancies (ages 5–16 years) following intravenous (IV) bolus injections. The pharmacolinetic data were analyzed by a non-linear leastsquare regression program NONLIN. A three-compartment open model fitted the raw data better than a two-compartment model in three patients. In the other patient the raw data fitted a two-compartment open model. The half-lives of the triphasic decay curves a, β, and γ were 2.6, 41, and 1,531 min (25.5 h), respectively. The mean apparent volume of the central compartment was 3.25 l, and the volume of distribution per 1.73 m² body surface area at steady state was 215.9 l. In a three-compartment open model, the first-order distribution and elimination rate constants (min^-1 of vincristine were as folows: k₁₂, 0.088; k₁₃, 0.121; k₂₁, 0.028; k₃₁, 0.0026; k₁₀, 0.045). The plasma clearance was 146.2 ml/min per 1.73 m², while the AUC ^∞₀ was 27,816 nM · min. Urinary excretion in one patient demonstrated a drug concentration of >1.0×10^-7 M in the urine up to 78 h after the injection. Up to 37% of the administered drug was excreted in the urine as vincristine and/or its metabolites by 90 h. The low elimination rate constant from poorly perfused tissues to blood plasma (k₃₁), a large apparent volume of distribution, and a long biological half-life (25.5 h) indicate avid tissue binding from which a slow release of the drug from the body tissues occurs.