Inhibitory effects of sesamin on CYP2C9-dependent 7-hydroxylation of S-warfarin.

Miharu Fujii, Kaori Yasuda, Toshiyuki Sakaki

Drug metabolism and pharmacokinetics 2020 Aug

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A recent report demonstrated that sesamin strongly and non-competitively inhibits S-warfarin 7-hydroxylation activity in human liver microsomes with a Ki value of 0.2 μM. This finding suggests that sesamin predominantly binds to CYP2C9 at another site for which it has a higher affinity than its affinity for the active site, thereby inhibiting the activity of CYP2C9 non-competitively. In this study, we found that sesamin competitively inhibited the 7-hydroxylation activity of S-warfarin in human liver microsomes with a Ki value of 15.7 μM. In addition, the recombinant CYP2C9-dependent 7-hydroxylation activity of S-warfarin was competitively inhibited by sesamin with a Ki value of 13.1 μM. These results are consistent with the fact that sesamin is a good substrate of CYP2C9, and its activity follows Michaelis-Menten kinetics. As the plasma concentration of sesamin after its administration is usually lower than 0.01 μM, the inhibition of S-warfarin metabolism by sesamin does not appear to be severe. Copyright © 2020 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Citation

Miharu Fujii, Kaori Yasuda, Toshiyuki Sakaki. Inhibitory effects of sesamin on CYP2C9-dependent 7-hydroxylation of S-warfarin. Drug metabolism and pharmacokinetics. 2020 Aug;35(4):368-373