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KMID : 0369820140440060401
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Jorunal of Korean Pharmaceutical Sciences
2014 Volume.44 No. 6 p.401 ~ p.409
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Evaluation of drug--drug interaction potential between DA-9801 and metformin
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Jeong Hyun-Uk
Kang Hee-Eun
Choi Sang-Zin
Son Mi-Won
Song Im-Sook
Lee Hye-Suk
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Abstract
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DA-9801, the mixture extract of Dioscorea 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. To assess potential drug?drug interactions between DA-9801 and metformin, we investigated the in vitro inhibitory potency of DA-9801 on metformin uptake in HEK293 cells overexpressing organic cation transporter (OCT) 1 and 2. DA-9801 inhibited OCT1- and OCT2-mediated metformin uptake in a concentration dependent manner and IC50 values for OCT1 and OCT2 were 41.8 and 108.9 μg/ml, respectively. Dioscorea nipponica Makino extract showed an inhibitory effect on OCT1- and OCT2-mediated metformin uptake and IC50 values were 33.8 and 87.1 μg/ml, respectively, which were similar to IC50 values of DA-9801. However, Dioscorea rhizoma extract slightly inhibited OCT1- and OCT2-mediated metformin uptake. The results suggest that the inhibitory effect of DA-9801 on OCT1 and OCT2 was attributable to the Dioscorea nipponica Makino extract but not to the Dioscorea rhizoma extract. However, pharmacokinetic properties of metformin measured in rats were unchanged by the co-administration of oral or intravenous DA-9801. In conclusion, DA-9801 moderately inhibited transport activity of OCT1 and OCT2 but did not show significant in vivo drug?drug interaction potential with metformin at its highest effective dose in rats.
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KEYWORD
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DA-9801, Metformin, OCT (organic cation transporter), Drug?drug interaction
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