Clinical pharmacokinetics of vindesine

The pharmacokinetics of vindesine were investigated in five patients with advanced cancer who were described by a triphasic serum decay curve compatible with a three-compartment open mammillary model. Serum half-lives were 2 min, 50 min, and 24 h for the fast, middle, and slow phases, respectively. The volume of the central compartment approximated the plasma volume in all patients studied. Distribution occurred quickly into a superficial tissue compartment in fairly rapid equilibrium with the plasma compartment, and also into a deep tissue compartment with slower redistribution to the central compartment. The large apparent volume of distribution and long elimination half-live suggest extensive tissue sequestration or delayed excretion of the drug in man. The slightly increased serum half-life of vindesine compared with published results for vinblastine may account for the greater degree and longer duration of marrow suppression seen clinically with vindesine.