Pharmacokinetic modeling of cisplatin disposition in children and adolescents with cancer

Abstract

A flow-limited physiologic pharmacokinetic model using volume terms, flow rates, distribution ratios, metabolic rate constants, and clearance terms restricted to physiologic or measured values was used to simulate the disposition of cisplatin in children and adolescents. Physiologic model simulations of parent cisplatin and total platinum serum concentrations were not statistically different from concentrations of these platinum species measured in 14 patients. A simplified first-order multicompartment operational model was also developed, and produced comparable simulations of parent cisplatin disposition but less accurate simulations of total platinum serum concentrations. These data provide further clarification of cisplatin disposition in humans and provide the basis for previously observed changes in the renal clearance of total platinum.