Distribution and transmembrane transport as the basis of proper pharmacodynamics of an antithrombotic drug - An indolinone derivative Valerevich Bykov Vladimir1,*, Vladimirovna Bykova Arina1,2, Andreevich Leonov Klim1, Isaakovich Vengerovskii Alexander2, Vasilevich Udut Vladimir3 1Innovative Pharmacological Research LLC, Tomsk, St. Elizarovs 79/4, RussiaRussian Federation 2Siberian State Medical University, Tomsk, Moskovsky Trakt, 2, RussiaRussian Federation 3Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk, St. Lenin 3, RussiaRussian Federation *Corresponding Author E-mail: vladimir.b.1989@gmail.com
Online published on 14 June, 2022. Abstract The goal of the present study: assess the distribution and transmembrane transport of an antiaggregant drug GRS of indolinone series. The distribution of an indolinone derivative in organs, between blood plasma and blood cells was studied in Sprague Dawley rats. A Thermo Scientific Pierce dialysis system was used to study the binding to blood plasma proteins. A Multi Screen Caco-2 test system was used to study the transmembrane transfer of the indolinone derivative. Quantitative assay of GRS was performed by an HPLC/MS method. GRS was shown to pass into the liver, heart and kidneys, and doesn't pass into the brain and skeletal muscle. The highest GRS accumulation occurs in the liver, the lowest in the kidneys. GRS has low plasma protein binding and its concentration is 1.6 times higher in blood cells than in blood plasma. GRS in 1 mcmol concentration has low cell membrane permeability from apical to basolateral membrane (A-B), increasing the concentration gradient by 10 times leads to a corresponding increase in transport efficiency. In the reverse direction (B-A) GRS permeability is 8.8 times higher, showing its participation in active transport. Pgp inhibitor cyclosporin A considerably decreases the transport efficiency of GRS in B-A direction. Top Keywords GRS, Antiplatelet, Indolinone derivative, Pharmacokinetics, Distribution. Top |