The comparative clinical pharmacology and pharmacokinetics of vindesine, vincristine, and vinblastine in human patients with cancer.

The pharmacokinetics of vindesine, vincristine, and vinblastine were investigated in patients with cancer. All drugs were administered rapidly via intravenous injection, and drug levels were determined in serum obtained at intervals after injection by radioimmunoassay. All three drugs exhibited a triphasic serum decay pattern, with no major differences in alpha or beta phase half-lives noted among them. However, vincristine had a longer and more variable terminal phase half-life (85 +/- 69 hr) than vindesine (24 +/- 10 hr) or vinblastine (25 +/- 7 hr). Central compartment volumes were also different. The most important finding was the observation of differences in the serum or body clearances of these drugs (vincristine 0.106 liter/kg/hr, vindesine 0.252 liter/kg/hr, and vinblastine 0.740 liter/kg/hr). These differences correlate well with the results of similar studies done in animals, with acute LD50 data in mice, and with the usually employed weekly clinical doses for these drugs. These findings support the hypothesis that differences in the toxicities of these alkaloids may be related in part to differences in their pharmacokinetics.