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KMID : 0370220180620040226
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Yakhak Hoeji
2018 Volume.62 No. 4 p.226 ~ p.236
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Effect of DA-9801 on the Expression of Drug-metabolizing Enzymes and Transporters in Human Hepatocytes
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Lee Hye-Suk
Lee Ji-Young
Cho Yong-Yeon
Jeong Hyeon-Uk
Ji Hye-Young
Choi Sang-Zin
Son Mi-Won
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Abstract
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DA-9801, a mixed extract of Dioscoreae japonica and Dioscorea nipponica Makino, is awaiting phase 3 clinicalstudy for the prevention or treatment of diabetic neuropathy in USA. To investigate whether DA-9801 acts as a perpetratorin drug interactions or not, we evaluated the mRNA induction of phase I and II drug metabolizing enzymes, including cytochromeP450 (CYP), UDP-glucuronosyltransferases (UGT) and sulfotransferases (SULT), and drug transporters. ThemRNA levels of phase I and II enzymes and transporters were analyzed by real-time PCR using three different cryopreservedhuman hepatocytes using specific primer and probe primer sets. We found that no significant alteration of themRNA expression was observed in phase I enzymes including CYP1A2, CYP3A4, CYP2B6, CYP2C8, and CYP2C9, phaseII enzymes such as UGT1A1, UGT1A4, UGT1A9, UGT2B7 and SULT2A1, and drug transporters including p-glycoprotein,MRP2, BCRP and OCT1 by DA-9801 treatment compared with vehicle treated control cells. Moreover, we found thatCYP1A2-catalyzed phenacetin O-deethylase, CYP2B6-catalyzed bupropion hydroxylase, and CYP3A4-catalyzed midazolam1’-hydroxylase activities were not interfered by DA-9801 in cryopreserved human hepatocytes. These results suggestedthat DA-9801 might not cause pharmacokinetic-based drug interactions with concurrent drugs which are the substrates ofthese drug metabolizing enzymes and transporters in humans.
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KEYWORD
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DA-9801, drug?drug interactions, human hepatocytes, CYP, UGT, transporters
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