A model for the action of vinblastine in vivo

Abstract

A model for the action of vinblastine (VLB) on cells multiplying exponentially in vivo with a generation time, T(G), has been derived. It is based on the assumption that cells attempting to pass through mitosis in the presence of VLB lose their proliferative capacity and that this lethal effect occurs only when the cells are exposed to a concentration of VLB which is above a critical value, C(k). The model leads to two predictions. First, that the percentage of cells surviving at any time after exposure to a dose, D, of VLB is 100% if D < D(k) and decreases to 0% after a time, T(G), following a dose D >/= D(k).2(T G/T1/2), where D(k) represents the dose of VLB required to produce the concentration C(k), and T(1/2) is the half-life of the VLB in vivo. Second, that the time, T(G), at which the percentage of cells surviving an exposure to VLB, at doses greater than D(k).2(U G/T1/2), decreases to zero should be equal to the generation time of the cells. Both of these predictions were confirmed experimentally which indicates that the model adequately explains the action of VLB in vivo.