Pharmacokinetics of etoposide (VP16) in children and adolescents with refractory solid tumors.

The clinical pharmacokinetics of etoposide were studied in eight pediatric patients with refractory solid tumors. The alpha-phase half-life, beta-phase half-life, volume of distribution, and elimination rate constant averaged 0.82 hr, 6.5 hr, 4.0 liters/sq m, and 0.25 hr-1, respectively. Noncompartmental parameters such as systemic clearance, mean residence time, and volume of distribution at steady-state averaged 20.9 ml/min/sq m, 7.8 hr, and 7.2 liters/sq m, respectively. A significant relationship between serum glutamic pyruvic transaminase and systemic clearance was observed, with patients having elevated serum glutamic pyruvic transaminase showing slower systemic clearance of etoposide. Systemic clearance, mean residence time, and beta-phase half-life of etoposide were significantly lower in those patients who had received cisplatin prior to their Phase II etoposide trial. The average pharmacokinetic values derived from these eight pediatric patients with solid tumors did not differ significantly from those previously reported in children with leukemia administered similar dosages and in adults given radioactively labeled etoposide.