PHARMACOKINETICS OF VINDESINE AND VINCRISTINE IN HUMANS

Abstract

Vindesine, a new phase 1 antitumor Vinca alkaloid congener, exhibited serum pharmacokinetic behavior in humans compatible with a 3 compartment, open mammillary model. The kinetic parameters included: t1/2 .alpha. = 3.24 .+-. 1.14 min, t1/2 .beta. = 99.0 .+-. 44.5 min, t1/2 .gamma. = 1213 .+-. 493 min, Vc (V.alpha.) = 4.81 .+-. 2.12 l, V.beta. = 58.2 .+-. 50.5 l, V.gamma. = 598 .+-. 294 l. Vincristine, studied only for the first 4 h, behaved like a 2 compartment system, with values of t1/2 .alpha. = 3.37 .+-. 0.72 min, t1/2 .beta. = 155 .+-. 18 min, V.alpha. = 4.53 .+-. 0.49 l, and V.beta. = 57.3 .+-. 21.1 l. Urine excretion data demonstrated that most drug elimination occurred within the first 24 h and amounted to 13.2 .+-. 5.9% for vindesine and 9.5 .+-. 5.1% for vincristine.