Inhibitory effect of glyburide on human cytochrome p450 isoforms in human liver microsomes.
The inhibitory effect of glyburide [International Nonproprietary Name (INN), glibenclamide] on CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 activities was evaluated using pooled human liver microsomes. Glyburide strongly inhibited CYP2C9-catalyzed S-warfarin and phenytoin metabolism in a competitive manner, with Ki (IC50) values of 2.4 (11.3) microM and 3.1 (9.4) microM, respectively. CYP3A4-catalyzed midazolam 1-hydroxylation was inhibited by glyburide with a Ki (IC50) value of 42.5 (90.0) microM. However, glyburide showed no appreciable inhibitory effect on CYP1A2, CYP2C8, CYP2C19, CYP2E1, or CYP2D6. In summary, glyburide showed potent inhibition on CYP2C9 and weak inhibition on CYP3A4, whereas it had minimal or no inhibitory effect on the other cytochromes p450 examined. It is anticipated that clinically significant drug-drug interactions will ensue when glyburide is coadministered with agents that are cleared primarily by the CYP2C9-mediated pathway and those with narrow therapeutic ranges.
Kim
Kyoung-Ah
KA
East-West Medical Research Institute, Kyunghee University, Seoul, Korea.
Park
Ji-Young
JY
D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D005905:Glyburide