Archives of Pharmacal Research

, Volume 36, Issue 1, pp 1–5

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

Authors

  • Hye Young Ji
    • College of Pharmacy and Integrated Research Institute of Pharmaceutical SciencesThe Catholic University of Korea
  • Kwang Hyeon Liu
    • College of Pharmacy and Research Institute of Pharmaceutical SciencesKyungpook National University
  • Tae Yeon Kong
    • College of Pharmacy and Integrated Research Institute of Pharmaceutical SciencesThe Catholic University of Korea
  • Hyeon-Uk Jeong
    • College of Pharmacy and Integrated Research Institute of Pharmaceutical SciencesThe Catholic University of Korea
  • Sang-Zin Choi
    • Research CenterDong-A Pharmaceutical Co.
  • Miwon Son
    • Research CenterDong-A Pharmaceutical Co.
  • Yong-Yeon Cho
    • College of Pharmacy and Integrated Research Institute of Pharmaceutical SciencesThe Catholic University of Korea
    • College of Pharmacy and Integrated Research Institute of Pharmaceutical SciencesThe Catholic University of Korea
    • Drug Metabolism & Bioanalysis Lab., College of PharmacyThe Catholic University of Korea
Report on Investigational Drugs

DOI: 10.1007/s12272-013-0014-9

Cite this article as:
Ji, H.Y., Liu, K.H., Kong, T.Y. et al. Arch. Pharm. Res. (2013) 36: 1. doi:10.1007/s12272-013-0014-9

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-9801Cytochrome P450UDP-glucuronosyltransferaseHuman liver microsomesDrug–drug interaction

Copyright information

© The Pharmaceutical Society of Korea and Springer Science+Business Media Dordrecht 2013