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

Kyoung Ah Kim, Ji-Young Park

Research output: Contribution to journalArticle

30 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 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.

Original languageEnglish
Pages (from-to)1090-1092
Number of pages3
JournalDrug Metabolism and Disposition
Volume31
Issue number9
DOIs
Publication statusPublished - 2003 Sep 1
Externally publishedYes

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Glyburide
Liver Microsomes
Cytochrome P-450 Enzyme System
Protein Isoforms
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP2E1
Cytochrome P-450 CYP1A2
Cytochrome P-450 CYP2D6
Midazolam
Phenytoin
Warfarin
Hydroxylation
Drug Interactions
Inhibitory Concentration 50
Names
Cytochrome P-450 CYP2C9
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Inhibitory effect of glyburide on human cytochrome P450 isoforms in human liver microsomes. / Kim, Kyoung Ah; Park, Ji-Young.

In: Drug Metabolism and Disposition, Vol. 31, No. 9, 01.09.2003, p. 1090-1092.

Research output: Contribution to journalArticle

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