BINDING OF A NEW MULTIDRUG-RESISTANCE MODULATOR, S9788, TO HUMAN PLASMA-PROTEINS AND ERYTHROCYTES

The interactions of S9788 with human plasma proteins have been investigated in vitro by an erythrocyte partitioning technique that allows an estimation of the plasma proteins and erythrocytes binding parameters. S9788 was 98% bound to plasma and blood. Lipoproteins bound S9788 with high affinities (binding constants of 0.645, 12.8 and 87.0 x 10(6) M(-1) for HDL, LDL and VLDL, respectively) and accounted for more than 55% of the total circulating S9788. Albumin and alpha(1)-acid glycoprotein also bound S9788 with lower binding constants of 0.022 and 0.245 x 10(6) M(-1). S9788 was mainly distributed in the plasma blood compartment (75-80%) with blood-to-plasma concentrations ratio of 0.6 to 0.7. These results indicate that, in vivo, the fraction of blood S9788 available for tissue diffusion, i.e., the free drug fraction in blood, should depend on lipoprotein concentration in plasma.