Effects of etodolac on P450 isoform-specific activities in human hepatic microsomes.
The effects of etodolac (CAS 41340-25-4) on P450 isoform-specific activities in human hepatic microsomes were examined. Etodolac had little effect on 7-ethoxyresorufin O-deethylation (CYP1A2), coumarin hydroxylation (CYP2A6), 7-benzyloxyresorufin O-debenzylation (CYP2B6), S-mephenytoin hydroxylation (CYP2C19), bufuralol hydroxylation (CYP2D6), chlorzoxazone hydroxylation (CYP2E1) and nifedipine oxidation (CYP3A4) at concentrations ranging from 10 to 50 micromol/L. Etodolac inhibited tolbutamide hydroxylation (CYP2C9) with the Ki value of 64 micromol/L, suggesting that it is a weak inhibitor of CYP2C9. The in vivo drug interaction was predicted from the in vitro data using the [I]/([I] + Ki) value. Because the value was calculated to be almost 1, it is not likely that etodolac causes the drug interactions with the CYP2C9 substrates.
Nakamura
Akio
A
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto Japan. ak.nakamura@po.nippon-shinyaku.co.jp
Tougou
Katsuhiko
K
Kitazumi
Hiroko
H
Yamada
Tetsuhiro
T
Honjou
Kumiko
K
Zinno
Asumi
A
Nonaka
Kiyoko
K
Mukai
Hideya
H
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D017308:Etodolac / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology*; D009249:NADP / Q000378:metabolism; D013379:Substrate Specificity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D017308:Etodolac; D009249:NADP; D003577:Cytochrome P-450 Enzyme System