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KMID : 0861120130170020139
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Korean Journal of Oriental Preventive Medicine
2013 Volume.17 No. 2 p.139 ~ p.155
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Effect of Gongjindan, a Traditional Korean Polyherbal Formula, on the Pharmacokinetics Profiles of Donepezil in Male SDRats (2) ― Single Oral Combination Treatment of Donepezil 10mg/kg with Gongjindan 100mg/kg, 1.5hr-intervals with 7-day Repeated Treatment ―
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Kwon Oh-Dae
Chung Dae-Kyoo
Park Soo-Jin
Ku Sae-Kwang
Lee Young-Joon
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Abstract
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Purpose : This study was aim to evaluate effects of pharmacodynamics and toxicity in combination therapy of donepezil with Gongjindan. The effects of Gongjindan co-administration on the pharmacokinetics (PK) of donepezil were observed after single and 7-day repeated oral co-administration with 1.5 hr-intervals, to evaluate synergic pharmacodynamics and reduce toxicity of combination therapy of donepezil with Gongjindan.
Materials and Methods : After 10 mg/kg of donepezil treatment, Gongjindan 100 mg/kg was administered with 1.5 hr-intervals.The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of first and last 7th donepezil treatment, and plasma concentrations of donepezil were analyzed using LC-MS/MS methods.
Results : Gongjindan markedly inhibited the absorption of donepezil regardless of sample time, from 30 min to 8hrs after end of first 1.5 hr-interval co-administration as compared with donepezil single treated rats. Especially the absorption of donepezil was significantly decreased at 2, 4, 6 and 8 hrs after coadministration as compared with donepezil single tre ated rats. Accordingly, the Cmax (-26.236%), AUC0-t (-26.02%) and AUC0-inf (-25.90%) of donepezil in 1.5 hr-interval co-administered rats were dramatically decreased as compared with donepezil single treated rats, respectively. However, no meaningful changes on the plasma donepezil concentrations and pharmacokinetic parameters were detected after end of last 7th 1.5 hr-interval co-administration as compared with donepezil single treatedrats, except for non-significant slight increases of Tmax (16.67%) detected in co-administered rats as compared with donepezil single treated rats.
Conclusion : These findings are considered as direct evidences that Gongjindan also decreased oral bio availability of donepezil as inhibited the absorptions, when they were co-administered with 1.5 hr intervals, but they maybe adapted after 7 days continuous repeated 1.5 hr-interval co-administration.
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KEYWORD
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Gongjindan, Pharmacokinetics, Drug-drug interactions, Rat, Donepezil, Repeat oral dose
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