Evaluation of DA-9801, a new herbal drug for diabetic neuropathy, on metabolism-mediated interaction.
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 IC(50) 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 IC(50) 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.
College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 420-743, Korea.
Hye Young
HY
Ji
Kwang Hyeon
KH
Liu
Tae Yeon
TY
Kong
Hyeon-Uk
HU
Jeong
Sang-Zin
SZ
Choi
Miwon
M
Son
Yong-Yeon
YY
Cho
Hye Suk
HS
Lee
D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D041743:Herb-Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D028321:Plant Preparations / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use
D065607:Cytochrome P-450 Enzyme Inhibitors; C562027:DA-9801; D028321:Plant Preparations; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase