Vindesine, a new Phase 1 Vinca alkaloid congener, exhibited serum pharmacokinetic behavior in humans compatible with a three-compartment, open mammillary model. The kinetic parameters included: t1/2 α = 3.24 ± 1.14 min, t1/2 β = 99.0 ± 44.5 min, t1/2 γ = 1213 ± 493 min, Vc (Vα) = 4.81 ± 2.12 liters, Vβ = 58.2 ± 50.5 liters, Vγ = 598 ± 294 liters. Vincristine, studied only for the first 4 hr, behaved like a two-compartment system, with values of t1/2 α = 3.37 ± 0.72 min, t1/2 β = 155 ± 18 min, Vα = 4.53 ± 0.49 liters, and Vβ = 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.

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This research was supported in part by USPHS Grant CA-16157 from the National Cancer Institute, NIH, and in part by Eli Lilly and Co.

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