Inhibitory effect of glyburide on human cytochrome P450 isoforms in human liver microsomes

Kyoung Ah Kim; Ji Young Park

doi:10.1124/dmd.31.9.1090

Inhibitory effect of glyburide on human cytochrome P450 isoforms in human liver microsomes

Kyoung Ah Kim, Ji Young Park

Research output: Contribution to journal › Article › peer-review

34 Citations (Scopus)

Abstract

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 K_i (IC₅₀) values of 2.4 (11.3) μM and 3.1 (9.4) μM, respectively. CYP3A4-catalyzed midazolam 1-hydroxylation was inhibited by glyburide with a K_i (IC ₅₀) value of 42.5 (90.0) μM. 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.

Original language	English
Pages (from-to)	1090-1092
Number of pages	3
Journal	Drug Metabolism and Disposition
Volume	31
Issue number	9
DOIs	https://doi.org/10.1124/dmd.31.9.1090
Publication status	Published - 2003 Sep 1

ASJC Scopus subject areas

Pharmacology
Pharmaceutical Science

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title = "Inhibitory effect of glyburide on human cytochrome P450 isoforms in human liver microsomes",

abstract = "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) μM and 3.1 (9.4) μM, respectively. CYP3A4-catalyzed midazolam 1-hydroxylation was inhibited by glyburide with a Ki (IC 50) value of 42.5 (90.0) μM. 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.",

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AB - 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) μM and 3.1 (9.4) μM, respectively. CYP3A4-catalyzed midazolam 1-hydroxylation was inhibited by glyburide with a Ki (IC 50) value of 42.5 (90.0) μM. 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.

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Inhibitory effect of glyburide on human cytochrome P450 isoforms in human liver microsomes

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