Report on Investigational Drugs

Archives of Pharmacal Research

, Volume 36, Issue 1, pp 1-5

First online:

Evaluation of DA-9801, a new herbal drug for diabetic neuropathy, on metabolism-mediated interaction

  • Hye Young JiAffiliated withCollege of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea
  • , Kwang Hyeon LiuAffiliated withCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University
  • , Tae Yeon KongAffiliated withCollege of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea
  • , Hyeon-Uk JeongAffiliated withCollege of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea
  • , Sang-Zin ChoiAffiliated withResearch Center, Dong-A Pharmaceutical Co.
  • , Miwon SonAffiliated withResearch Center, Dong-A Pharmaceutical Co.
  • , Yong-Yeon ChoAffiliated withCollege of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea
  • , Hye Suk LeeAffiliated withCollege of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of KoreaDrug Metabolism & Bioanalysis Lab., College of Pharmacy, The Catholic University of Korea Email author 

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Abstract

DA-9801, the mixture extract of Dioscoreae rhizoma and Dioscorea nipponica Makino, is a new herbal drug currently being evaluated in a phase II clinical study for the treatment of diabetic peripheral neuropathy in Korea. The inhibitory potentials of DA-9801, D. rhizoma extract, D. nipponica Makino extract, and dioscin, an active component of DA-9801, on eight human cytochrome P450 (CYP) enzymes and four UDP-glucuronosyltransferase (UGT) enzymes were investigated in human liver microsomes using liquid chromatography–tandem mass spectrometry. DA-9801 showed slight inhibition of CYP1A2, CYP2C8, UGT1A1, and UGT1A9 enzyme activities with IC50 values of 396.4, 449.9, 226.0, and 408.8 μg/mL, respectively. D. rhizoma extract showed negligible inhibition of CYP and UGT activities, but D. nipponica extract slightly inhibited CYP1A2, CYP2C8, CYP2C9, UGT1A1, and UGT1A9 activities with IC50 values of 264.2, 237.1, 206.8, 302.4, and 383.1 μg/mL, respectively. DA-9801 showed volume per dose index values of 0.44–0.88 L for a 200-mg dose, suggesting that they may not cause the inhibition of the metabolism of CYP1A2, CYP2C8, UGT1A1, and UGT1A9-catalyzed drugs in humans. These results suggest that the administration of DA-9801 in human may not cause clinically relevant inhibition of these enzymes.

Keywords

DA-9801 Cytochrome P450 UDP-glucuronosyltransferase Human liver microsomes Drug–drug interaction