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KMID : 0861120140180020089
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Korean Journal of Oriental Preventive Medicine
2014 Volume.18 No. 2 p.89 ~ p.100
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Effect of Gongjindan, a Polyherbal Formula on the Pharmacokinetics Profiles of Sorafenib in Male SD Rats (1) - Single Oral Combination Treatment of Sorafenib 50mg/kg with Gongjindan 100mg/kg within 5min -
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Kim Seung-Mo
Lee Chang-Hyeong
Park Soo-Jin
Kang Su-Jin
Song Chang-Hyun
Ku Sae-Kwang
Lee Young-Joon
Han Chang-Hyun
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Abstract
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Objective : The co-administration effects of Gongjindan (GJD) on the pharmacokinetics (PK) of sorafenib wereobserved as a process of the comprehensive and integrative medicine.
Methods : After sorafenib treatment, GJD was administered within 5 min. The plasma were collected at30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of GJD treatment, and plasmaconcentrations of sorafenib were analyzed using LC-MS/MS methods. PK parameters of sorafenib (Tmax,Cmax, AUC, t1/2 and MRTinf) were analysis as compared with sorafenib single administered rats.
Results : The absorption of sorafenib were significantly increased at 30min, 1, 6 and 6hrs after coadministrationwith GJD as compared with sorafenib single treated rats. Accordingly, the AUC0-t (47.20%)of sorafenib was significantly increased but t1/2 (-30.63%) and MRTinf (-34.11%) in co-administered rats werenon-significantly decreased. These findings are considered as direct evidences that GJD increased the oralbioavailability of sorafenib through increase of the absorption, when they co-administered within 5min.
Conclusion : Based on the results, co-administration of GJD increased the oral bioavailability of sorafenibthrough increase of the gastrointestinal absorption. It is considered that the more detail pharmacokineticstudies should be tested to conclude the effects of GJD on the pharmacokinetics of sorafenib, when theywere co-administered, like the effects after co-administration with reasonable intervals considering theTmax of sorafenib (about 3.5hr-intervals) and after repeated co-administrations.Hence, concomitant uses ofGJD with sorafenib may require close monitoring for potential drug interactions.
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KEYWORD
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Gongjindan, Pharmacokinetics, Drug-drug interactions, Rat, Sorafenib, Nexavar
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