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KMID : 0861120130170010077
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Korean Journal of Oriental Preventive Medicine
2013 Volume.17 No. 1 p.77 ~ p.88
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Effect of Gongjindon a Traditional Korean Polyherbal Formula, on the Pharmacokinetics Profiles of Donepezil in Male SDRats (1) -Single Oral Combination Treatment of Donepezil 10mg/kg with Gongjindan 100mg/kg within 5 min -
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Chung Dae-Kyoo
Kwon Oh-Dae
Park Soo-Jin
Ku Sae-Kwang
Lee Young-Joon
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Abstract
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Objectives : This study was aim to evaluate effects of pharmacodynamics and toxicity in combination therapy of donepezil with Gongjindan.
Methods : After 10mg/kg of donepezil treatment, Gongjindan 100mg/kg was administered within 5 min. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of Gongjindan treatment, and plasma concentrations of donepezil were analyzed using LC-MS/MS methods. PK parameters of donepezil were analysis as compared with donepezil single administered rats.
Results : Gongjindan markedly inhibited the absorption of donepezil regardless of sample time, from 30min to 8hrs after end of co-administration comparing with donepezil single treated rats. Especially the absorption of donepezil was significantly decreased at 2hrs after co-administration as compared with donepezil single treated rats, in the present study. Accordingly, the Cmax(-27.76%), AUC0-t(-27.22%) and AUC0-inf(-26.54%) of donepezil in co-administered rats were significantly decreased as compared with donepezil single treated rats, respectively.
Conclusions : Based on the results of the present study, co-administration of Gongjindan decreases the oral bioavailability of donepezil by inhibiting the absorption. It is considered that the more detail pharmacokinetic studies should betested to conclude the effects of Gongjindan on the pharmacokinetics of donepezil, when they were co-administered, like the effects after co-administration with reasonable intervals considering the Tmax of donepezil and after repeated co-administrations
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KEYWORD
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Gongjindan, Pharmacokinetics, Drug-drug interactions, Rat, Donepezil
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