Anti-Leukemia Drug Chlorogenic Acid Exerts Strong Inhibition on the Activity of Phase II Drug-Metabolizing Enzymes (DMEs)

作者：Wang, Bing-Hua; Wang, Li; Ma, Jun-Jie; Li, Kai-Min^*

来源：Latin American Journal of Pharmacy, 2017, 36(1): 188-191.

• chlorogenic acid (CGA)
• drug-drug interaction (DDI)
• leukemia
• safety

Leukemia remains to be one of the most severe diseases to threaten the health of human, and.chlorogenic acid (CGA) is a drug candidate to treat leukemia. The present study aims to determine the inhibition of CGA on the activity of phase II drug-metabolizing enzymes (DMEs) UDP-glucuronosyltransferases (UGTs). In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was used to determine the inhibition of CGA on various isoforms of UGTs. The results showed that CGA did not exert significant inhibition on the activity of UGT1A6, 1A7, 1A8, 1A9, 2B4, and 2B17. In contrast, the activity of UGT2B15 was strongly inhibited by 100 1.01 of CGA. It should be noted that the in vivo inhibition magnitude was determined by both in vitro inhibition kinetics (inhibition type, inhibition parameters (IU)) and in vivo exposure of CGA. Therefore, these experiments should be carried out in the future. In conclusion, the present study demonstrated the strong inhibition of CGA on the activity of UGT2B15, indicating UGT2B15 inhibition-based drug-drug interaction.

• 出版日期2017-1
• 单位烟台毓璜顶医院