Clinical pharmacokinetics of vindesine |
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Authors: | R. L. Nelson R. W. Dyke M. A. Root |
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Affiliation: | (1) The Lilly Laboratory for Clinical Research, Wishard Memorial Hospital, 46202 Indianapolis, Indiana, USA;(2) School of Medicine, Wishard Memorial Hospital, Indiana University, 46202 Indianapolis, Indiana, USA;(3) Eli Lilly and Company, 46206 Indianapolis, Indiana, USA |
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Abstract: | Summary The pharmacokinetics of vindesine were investigated in five patients with advanced cancer who were receiving the drug. Following a rapid IV bolus dose, vindesine kinetics 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. |
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