CLINICAL PHARMACOKINETICS OF VINDESINE - REPEATED TREATMENTS BY INTRAVENOUS BOLUS INJECTIONS

Vindesine was administered i.v. to 12 patients with advanced cancer. Treatment was repeated after 2 wk or more with a 1.5- to 2-fold increased dose of vindesine. Five patients received 1 or 2 additional injections at the higher dose level. One patient was given 0.4, 1 and 4 mg of vindesine on days 1, 3 and 6 and then 8 mg on days 19 and 34. Plasma samples and urine were collected over 3 days after injection and monitored for vindesine by radioimmunoassay. Significant time-dependence of vindesine plasma concentration decay kinetics at a constant dose was observed in 4 of 6 patients. The comparison of the kinetics after administration of different doses to the same patient revealed frequent deviations from linearity with no obvious general trend. Urinary excretion was very low (1-12% of the dose); urinary excretion rates correlated with plasma concentrations. Renal clearances were variable from 1 patient to another and also for the same patient from 1 injection to another. These data were interpreted in terms of time- and dose-dependence of vindesine pharmacokinetics.