Metabolism of a New Antiaggregant, Indolinone Derivative
Bykov V. V., Leonov K. A., Serebrov V. Y., Chernysheva G. A., Smol’yakova V. I., Solov’ev M. A., Udut E. V., Fisenko V. P., Udut V. V.
Bulletin of Experimental Biology and Medicine
Vol.168, Issue6, P. 739-742
Опубликовано: 2020
Тип ресурса: Статья
DOI:10.1007/s10517-020-04792-y
Аннотация:
Cytochrome p450-mediated metabolism of GRS (indolinone antiaggregant) and its effects on activities of cytochrome p450 isoenzymes were studied. Inhibition of 6 isomers of cytochrome p450 in human liver microsomes was studied with the use of specific substrates. It was found that human liver cytochrome p450 enzymes could not induce degradation of GRS and that GRS was not an inductor or inhibitor of cytochrome p450 family members 1A2, 2C9, 2C19, 2D6, 2C8, and 3A4. Hence, clinical use of the prospective antiaggregant would not involve the risk of uncontrolled fluctuations in GRS concentrations in the organism because of interactions between the drugs. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
Ключевые слова:
antiaggregant; cytochrome p450; GRS; indolinone derivative; metabolism
2 [2 [5 (hydroxymethyl) 3 methyl 1,3 oxasolidine 2 ilidene] 2 cyano ethyllilidene] 1h indole 3(2h) one; cytochrome P450 1A2; cytochrome P450 2C19; cytochrome P450 2C8; cytochrome P450 2C9; cytochrome P450 2D6; cytochrome P450 3A4; cytochrome P450 isoenzyme; indole derivative; unclassified drug; verapamil; animal cell; Article; concentration response; controlled study; drug clearance; drug half life; drug metabolism; enzyme activity; human; human cell; IC50; in vitro study; liver microsome; nonhuman; rat
Язык текста: Английский
ISSN: 1573-8221
Bykov V. V.
Leonov K. A.
Serebrov V. Y.
Chernysheva G. A.
Smol’yakova V. I.
Solov’ev M. A.
Udut E. V.
Fisenko V. P. Vladimir Petrovich 1946-
Udut V. V.
Бyков В. В.
Леонов К. А.
Серебров В. Y.
Чернyшева Г. А.
Смол’якова В. И.
Солов’ев М. А.
Удут Е. В.
Фисенко В. П. Владимир Петрович 1946-
Удут В. В.
Metabolism of a New Antiaggregant, Indolinone Derivative
Текст визуальный непосредственный
Bulletin of Experimental Biology and Medicine
Springer New York Consultants Bureau
Vol.168, Issue6 P. 739-742
2020
Статья
antiaggregant cytochrome p450 GRS indolinone derivative metabolism
2 [2 [5 (hydroxymethyl) 3 methyl 1,3 oxasolidine 2 ilidene] 2 cyano ethyllilidene] 1h indole 3(2h) one cytochrome P450 1A2 cytochrome P450 2C19 cytochrome P450 2C8 cytochrome P450 2C9 cytochrome P450 2D6 cytochrome P450 3A4 cytochrome P450 isoenzyme indole derivative unclassified drug verapamil animal cell Article concentration response controlled study drug clearance drug half life drug metabolism enzyme activity human human cell IC50 in vitro study liver microsome nonhuman rat
Cytochrome p450-mediated metabolism of GRS (indolinone antiaggregant) and its effects on activities of cytochrome p450 isoenzymes were studied. Inhibition of 6 isomers of cytochrome p450 in human liver microsomes was studied with the use of specific substrates. It was found that human liver cytochrome p450 enzymes could not induce degradation of GRS and that GRS was not an inductor or inhibitor of cytochrome p450 family members 1A2, 2C9, 2C19, 2D6, 2C8, and 3A4. Hence, clinical use of the prospective antiaggregant would not involve the risk of uncontrolled fluctuations in GRS concentrations in the organism because of interactions between the drugs. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.