Binding of a new multidrug resistance modulator,S9788, to human plasma proteins and erythrocytes |
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Authors: | Saïk Urien Phuc Nguyen Gérard Bastian Catherine Lucas Jean-Paul Tillement |
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Affiliation: | (1) Laboratoire de Pharmacologie, Faculté de Médecine, Université Paris XII, France;(2) I.N.S.E.R.M., Paris, France;(3) Service d’Oncologie Médicale, Hopital Pitié Salpétrière, Paris, France;(4) I.R.I.S., Courbevoie, France;(5) Laboratiore de Pharmacologie, Faculté de Médecine, 8 rue du Général Sarrail, 94010 Créteil, France |
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Abstract: | Summary The interactions of S9788 with human plasma proteins have been investigatedin 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 87.0×106M−1 for, HDL, LDL and VLDL, respectively) and accounted for more than 55% of the total circulating S9788. Albumin and alpha1-acid glycoprotein also bound S9788 with lower binding constants of 0.022 and 0.245×106 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. |
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Keywords: | S9788 MDR reversion binding blood plasma binding |
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