BINDING OF A NEW VINCA ALKALOID DERIVATIVE, S12363, TO HUMAN PLASMA-PROTEINS AND PLATELETS - USEFULNESS OF AN ERYTHROCYTE PARTITIONING TECHNIQUE

The interactions of S12363 with human plasma proteins have been investigated in vitro by an erythrocyte partitioning technique that allows a quantitative estimation of the plasma and erythrocytes binding. S12363 was 85-95% plasma-bound and 97-98% blood-bound. The main binding protein in plasma was alpha-acid glycoprotein, with a binding constant of 0.6.10(6) M - 1, accounting for 70% of total S12363 in plasma. Owing to extensive binding to platelets (40-50% of total blood amount), S12363 was mainly distributed in the non plasma blood compartment, with blood-to-plasma concentrations ratio of 1.2-1.4. These results indicate that, in vivo, the fraction of blood S12363 available for tissue diffusion, i.e., the free drug fraction in blood, should depend on both alpha1-acid glycoprotein concentration in plasma and blood platelet count.