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 language | English |
|---|---|
| Pages (from-to) | 1090-1092 |
| Number of pages | 3 |
| Journal | Drug Metabolism and Disposition |
| Volume | 31 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2003 Sep 1 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Inhibitory effect of glyburide on human cytochrome P450 isoforms in human liver microsomes
AU - Kim, Kyoung Ah
AU - Park, Ji-Young
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=0042357521&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0042357521&partnerID=8YFLogxK
U2 - 10.1124/dmd.31.9.1090
DO - 10.1124/dmd.31.9.1090
M3 - Article
VL - 31
SP - 1090
EP - 1092
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
SN - 0090-9556
IS - 9
ER -