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 x 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 alpha 1-acid glycoprotein concentration in plasma and blood platelet count.
Urien
S
S
Laboratoire de Pharmacologie, Faculté de Médecine, Université Paris XII, France.
Bastian
G
G
Lucas
C
C
Bizzari
J P
JP
Tillement
J P
JP
D001792:Blood Platelets / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D001825:Body Fluid Compartments; D003956:Dialysis; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D009961:Orosomucoid / Q000378:metabolism; D011485:Protein Binding; D014748:Vinca Alkaloids / Q000097:blood*
D001798:Blood Proteins; D009961:Orosomucoid; D014748:Vinca Alkaloids; C064005:S 12363