PLATINUM ACCUMULATION IN ADULT CANCER-PATIENTS RECEIVING CONSECUTIVE INFUSIONS OF CISPLATIN

The pharmacokinetics of total plasma platinum (TP), ultrafilterable pl asma platinum (UF) and urinary excretion were studied in 15 patients r eceiving 2 consecutive 6-hour intravenous infusions of cisplatin (80 t o 100 mg/m(2)) at a dose interval of 3 weeks. After first drug exposur e, TP was slowly eliminated from plasma [terminal half-life (t1/2 gamm a) of 11.6 +/- 2.5 days]. On second drug exposure, the mean plasma cle arance and volume of distribution at steady-state decreased sig nifica ntly (p<0.001) from 0.15 to 0.11 L/h/m(2) and from 49.5 to 42.1 L/m(2) , respectively, but no significant change was observed in the t1/2 gam ma (11.6 to 12.6 days) or in the mean residence time (14.6 to 16.3 day s). A significant linear correlation was found between observed and pr edicted plasma levels of TP during the second course. The mean peak UF levels, the area under the concentration vs time curve from zero to i nfinity (AUC0-infinity) and urinary excretion (0 to 24 hours) were not significantly different between the 2 courses. The extent of reductio n in plasma clearance of TP over 3 drug infusions in 3 evaluated patie nts correlated with the development of ototoxicity.