Teniposide (VM26) Disposition in Children with Leukemia

Abstract The clinical pharmacokinetics of teniposide (VM-26, NSC 122819) has been studied in 21 children (median age, 4.7 years) with acute lymphocytic leukemia. Teniposide was administered at a dosage of 165 mg/sq m as a 30- to 60-min i.v. infusion. Patients were studied either on the first or second dosage of the drug. Plasma samples were assayed for teniposide and metabolites by high-performance liquid chromatography with electrochemical detection. Both compartmental and noncompartmental pharmacokinetic analyses were performed. Systemic clearance and apparent volume of distribution at steady state averaged 13.82 ± 6.0 ml/min/sq m (S.D.) and 7.9 ± 4.0 liter/sq m, respectively. Univariate and multivariate stepwise regression analyses were used to construct mathematical models to describe the relationships between certain patient-specific demogrphic and laboratory values and the pharmacokinetic parameters, systemic clearance, elimination rate constant, and area under the concentration-time curve. A significant relationship between serum alkaline phosphatase and systemic clearance, elimination rate constant, and area under the concentration-time curve was found, suggesting that liver function influences the disposition of this anticancer drug in humans.