대한예방한의학회지 (Journal of Society of Preventive Korean Medicine)

대한예방한의학회 (Society of Preventive Korean Medicine)
권호 표지

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 -

  • Kim, SeungMo (Department of Korean Internal Medicine of Hepatology, College of Korean Medicine, Daegu Haany University) ;
  • Lee, Chang Hyeong (Department of Internal Medicine, Daegu Catholic University Hospital) ;
  • Park, Soo Jin (The Medical Research center for Globalization of Herbal Formulation, Daegu Haany University) ;
  • Kang, Su Jin (Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University) ;
  • Song, Chang Hyun (The Medical Research center for Globalization of Herbal Formulation, Daegu Haany University) ;
  • Han, Chang Hyun (Center for Medical History and Literature, Korean Institute of Oriental Medicine) ;
  • Ku, Sae Kwang (The Medical Research center for Globalization of Herbal Formulation, Daegu Haany University) ;
  • Lee, Young Joon (Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University)
  • 투고 : 2014.07.05
  • 심사 : 2014.08.11
  • 발행 : 2014.08.31
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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 ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with sorafenib single administered rats. Results : The absorption of sorafenib were significantly increased at 30min, 1, 6 and 6hrs after co-administration with GJD as compared with sorafenib single treated rats. Accordingly, the $AUC_{0-t}$ (47.20%) of sorafenib was significantly increased but $t_{1/2}$ (-30.63%) and $MRT_{inf}$ (-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 $T_{max}$ 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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