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Pharmacokinetics of Vindesine and Vincristine in Humans¹

The Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 [R. J. O., F. O. H.], and Eli Lilly Research Laboratories, Indianapolis, Indiana 46206 [M. A. R.]

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: t_1/2 = 3.24 ± 1.14 min, t_1/2 ß = 99.0 ± 44.5 min, t_1/2 = 1213 ± 493 min, V_c (V) = 4.81 ± 2.12 liters, V_ß = 58.2 ± 50.5 liters, V = 598 ± 294 liters. Vincristine, studied only for the first 4 hr, behaved like a two-compartment system, with values of t_1/2 = 3.37 ± 0.72 min, t_1/2 ß = 155 ± 18 min, V = 4.53 ± 0.49 liters, and V_ß = 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.

¹ 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.

² To whom requests for reprints should be addressed, at The Johns Hopkins Oncology Center, 601 North Broadway, Baltimore, Md. 21205.

Received 12/15/76. Accepted 5/ 5/77.