Pharmacokinetic study of Cis-dichlorodiammine platinum II, in children after rapid infusion.

Abstract

This study involves 3 children ranging from 10 to 13 years and an eight-month-old infant who received Cis-DDP (30-100 mg/m2) every fourth week by means of a short-term infusion (20-35 minutes). Platinum levels in plasma and urine were determined by flameless atomic absorption spectrophotometry. The decrease in total plasma platinum is triphasic, consistent with the distribution expected for a 3 compartment model. In the elimination phase, the half-life values are high and vary between 149 and 541 hours. The total plasma clearances are extremely low and range from 0.027 to 0.187 litre/hour. The urinary excretion of platinum during the first 5 and 7 days respectively, in two children following administration of Cis-DDP results in large platinum concentrations (40-71 mg/litre) in the first urine excreted from each child. The cumulative urinary platinum excretion in the first twelve hours is high i. e. 27.2 to 32.5% of the administered dose but them it does not exceed 50% even after 5 days. These results confirm that after a short-term infusion of Cis-DDP in a single dose, the kidneys are suddenly subjected to platinum in high concentrations. In order to minimize the nephrotoxicity of this platinum complex, while maintaining sufficient plasma levels to ensure its anti-neoplastic activity, we recommend a schedule consisting of fractionated doses.