International Journal of Clinical Pharmacology & Pharmacotherapy Volume 5 (2020), Article ID 5:IJCPP-149, 8 pages
Original Article
Using Amodiaquine to Establish Efficient Metabolite Screening and Drugdrug Interaction System by Recombinant Human CYP2C8 Yeast

Qiyue Zhang1,#, He Zhu1,#, Hanhan Li1, Wen Qian2, Xijing Chen1, Toshiyuki Sakaki3 and Changqing Yang*,1

1School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
2Nanjing BRT-Biomed Company, Limited, Jiangning District, Nanjing, China
3Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, Kurokawa, Imizu, Toyama, Japan
Prof. Changqing Yang, Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China; E-mail:
#:Qiyue Zhang and He Zhu contributed equally to this work.
03 August 2020; 15 September 2020; 17 September 2020
Zhang Q, Zhu H, Li H, Qian W, Chen X, et al. (2020) Using Amodiaquine to Establish Efficient Metabolite Screening and Drug-drug Interaction System by Recombinant Human CYP2C8 Yeast. Int J Clin Pharmacol Pharmacother 5: 149.doi:
This work was supported by the fundamental research funds for “Double First-Class”Initiative Innovation Team Project of China Pharmaceutical University (grant No. CPU2018GY29).


Background: In the development of a new drug, pre-clinical studies require an efficient, convenient, and reliable evaluation system for metabolite screening and drug-drug interaction (DDI). Our study aimed to establish such a reliable evaluation system using recombinant human CYP2C8 (RHCYP2C8) yeast with the enzyme-selective substrate amodiaquine by optimizing enzyme-catalyzed reaction conditions. Then, we studied the inhibition of Gingerol Soft Capsule (GSC) and 6-gingerol (6G) on CYP2C8 activity.
Methods: RHCYP2C8 yeast whole-cell and microsome reaction systems were established by optimizing enzyme-catalyzed reaction parameters. IC50 values of 6G, GSC, and quercetin were calculated by GraphPad Prism 8.3.0, and their volume per dose index (VDI) values were calculated in order to predict the potential inhibition in vivo.
Results: Our results show that the enzyme kinetic parameters of the whole-cell reaction system for Km and Vmax were 89.77 μmol/L and 0.33 μmol/h•g yeast, the parameters of the microsome reaction system, were 6.20 μmol/L and 0.12 μmol/h•g protein, respectively. IC50 values of quercetin, 6G, and GSC were 6.370, 612.5 μmol/L, and 464 μg/mL, respectively. The VDI values of 6G and GSC <5.0, suggesting low potential for interaction.
Conclusion: The RHCYP2C8 yeast whole-cell reaction system is suitable for the metabolite screening, and the RHCYP2C8 microsome reaction system is efficient for the DDI study. The observed IC50 values of 6G and GSC are unlikely to be achieved in humans with oral administration according to the poor bioavailability documented. Thus, GSC or 6G might not be effective in causing potential DDIs with drugs metabolized by CYP2C8 in humans.