Pharmacokinetics of vindesine and vincristine in humans

Abstract

Vindesine, a new Phase 1 Vinca alkaloid congener, exhibited serum pharmacokinetic behavior in humans compatible with a three-compartment, open mammilary model. The kinetic parameters included: t1/2 alpha=3.24+/-1.14 min, t1/2beta=99.0+/-44.5 min, t1/2gamma=1213+/-493 min, Vc (Valpha)=4.81+/-2.12 liters, Vbeta=58.2+/-50.5 liters, Vgamma=598+/-294 liters. Vincristine, studied only for the first 4 hr, behaved like a two-compartment system, with values of t1/2 alpha=3.37+/-0.72 min, t1/2beta=155+/-18 min, Valpha=4.53+/-0.49 liters, and Vbeta=57.3+/-21.1 liters. Urine excretion data demonstrated that most drug elimination occurred within the first 24 hr and amounted to 13.2+/-5.9% for vindesine and 9.5+/-5.1% for vincristine.