VINORELBINE HIGH-AFFINITY BINDING TO HUMAN PLATELETS AND LYMPHOCYTES - DISTRIBUTION IN HUMAN BLOOD

Using [H-3]-vinorelbine, we demonstrated the presence of saturable and time-dependent high-affinity binding sites on human platelets and lymphocytes. The dissociation constant and binding-site values observed were 200 +/- 38 nM, 20.0 +/- 2.2 amol/platelet, and 155 +/- 20 amol/lymphocyte, respectively. Among other blood components, saturable low-affinity binding of vinorelbine to alpha1-acid glycoprotein, serum albumin, and lipoproteins was observed. The binding to erythocytes was nonsaturable. Given die relative concentrations of these carriers, vinorelbine mainly distributes in the platelet compartment in blood (>70%), and the amount of free vinorelbine in plasma relative to the total amount in blood is <2%. It is suggested that because of the preferential retention of vinorelbine by platelets, variations in the platelet count are very likely to produce changes in the free blood fraction of vinorelbine.