CONTINUOUS INFUSION OF HIGH-DOSE CISPLATIN IN CHILDREN - PHARMACOKINETICS OF FREE AND TOTAL PLATINUM

A pharmacokinetic study was carried out in two infants and two (older) children with high-dose cisplatin (CP) (40 mg/m2/day) by 5-day continuous infusion. Following interruption of the infusion, the decrease in total plasma platinum was biphasic, with a terminal half-life of 155.5-418 h. During administration the urinary concentrations were between 7.66 and 15.2 mg/l. Thirty to thirty five per cent of the administered dose was eliminated within 48 h of discontinuing infusion. Free platinum (FP) levels declined in a biphasic manner, with a mean (± S.E.) elimination half-life of 81.25 (± 34.9) h. FP was still detectable in the plasma 10 days after the end of infusion with levels above 0.010 μg/ml. FP availability, measured as the area under the curves (AUC) of the FP concentration-up to 2 h after ending the infusion-were 768 (± 326) μg.min/ml. Inter- or intra-individual differences in AUC values were not observed. © 1987.