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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 -

강수진|이영준|박수진|한창현|구세광|송창현|이창형|김승모
대한예방한의학회 (Society of Preventive Korean Medicine)|2014.08|대한예방한의학회지 (Society of Preventive Korean Medicine)|제18권 제2호|pp. 89-100

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PharmacokineticsDrug-drug interactionsRatSorafenibGongjindanNexavar
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초록

Objective : The co-administration effects of Gongjindan (GJD) on the pharmacokinetics (PK) of sorafenib were observed as a process of the comprehensive and integrative medicine. Methods : After sorafenib treatment, GJD 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 GJD treatment, and plasma concentrations 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 coadministration with 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 were non-significantly decreased. These findings are considered as direct evidences that GJD increased the oral bioavailability 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 sorafenib through increase of the gastrointestinal absorption. It is considered that the more detail pharmacokinetic studies should be tested to conclude the effects of GJD on the pharmacokinetics of sorafenib, when they were co-administered, like the effects after co-administration with reasonable intervals considering the Tmax of sorafenib (about 3.5hr-intervals) and after repeated co-administrations.Hence, concomitant uses of GJD with sorafenib may require close monitoring for potential drug interactions.

Abstract

Objective : The co-administration effects of Gongjindan (GJD) on the pharmacokinetics (PK) of sorafenib were observed as a process of the comprehensive and integrative medicine. Methods : After sorafenib treatment, GJD 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 GJD treatment, and plasma concentrations 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 coadministration with 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 were non-significantly decreased. These findings are considered as direct evidences that GJD increased the oral bioavailability 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 sorafenib through increase of the gastrointestinal absorption. It is considered that the more detail pharmacokinetic studies should be tested to conclude the effects of GJD on the pharmacokinetics of sorafenib, when they were co-administered, like the effects after co-administration with reasonable intervals considering the Tmax of sorafenib (about 3.5hr-intervals) and after repeated co-administrations.Hence, concomitant uses of GJD with sorafenib may require close monitoring for potential drug interactions.

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