Clinical pharmacokinetics of vindesine: repeated treatments by intravenous bolus injections.

Vindesine was administered intravenously to 12 patients with advanced cancer. Treatment was repeated after 2 weeks or more with a 1.5-to 2-fold increased dose of vindesine. Five patients received one or two 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 four patients out of six. 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), and urinary excretion rates correlated with plasma concentrations. Renal clearances were variable from one patient to another and also for the same patient from one injection to another. These data were interpreted in terms of time- and dose-dependence of vindesine pharmacokinetics.