Pharmacokinetics of vincristine, vinblastine, and vindesine in rhesus monkeys

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Abstract
The pharmacokinetics of vincristine, vindesine, and vinblastine following IV bolus doses of 0.05 mg, 0.10 mg, and 0.20 mg/kg body weight, respectively, were studied in adult male rhesus monkeys. The alkaloid concentrations were determined by a sensitive radioimmunoassay. Pharmacokinetic data were analyzed by a non-linear least-square regression program NONLIN, and the data fit a two-compartment open model. The average terminal half-lives of vincristine, vinblastine, and vindesine in the serum were 189, 152, and 175 min, respectively. The areas under the alkaloid concentration-time curve from 0 to ∞ for these drugs for a 1-mg dose were as follows: vincristine, 26,572 nM · min; vinblastine, 16,745 nm · min; and vindesine, 12,708 nM · min. The clearance rate (ml/min/kg) for vincristine (4.8) was slightly lower than that for vinblastine (7.0) or vindesine (7.8). The apparent volumes of distribution for vincristine, vinblastine, and vindesine were, respectively, 1.3, 1.5, and 1.9 l/kg body weight. In the two-compartment open model, the transfer rate constant from compartment 2 to compartment 1 (k21) was lower than the other rate constants (k10 and k12) for each of the alkaloids. The total average excretion of the alkaloids over a 4-day period in urine and feces for vincristine, vinblastine, and vindesine were, respectively, 36.7%, 18.2%, and 25.3% of the injected dose. These data indicate avid tissue retention of the Catharanthus alkaloids in this non-human primate. The similarities between these pharmacokinetic parameters and those previously reported for man suggest that the rhesus monkey is an ideal animal model in which to study the pharmacologic properties of these alkaloids.

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