title: Binding of a new vinca alkaloid derivative, S12363, to human plasma proteins and platelets. Usefulness of an erythrocyte partitioning technique.
abstract: 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.
authors: Laboratoire de Pharmacologie, Faculté de Médecine, Université Paris XII, France.
authors: S
authors: S
authors: Urien
authors: G
authors: G
authors: Bastian
authors: C
authors: C
authors: Lucas
authors: J P
authors: JP
authors: Bizzari
authors: J P
authors: JP
authors: Tillement
mesh_terms: 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*
chemical_list: D001798:Blood Proteins; D009961:Orosomucoid; D014748:Vinca Alkaloids; C064005:S 12363