Journal of Society of Preventive Korean Medicine (대한예방한의학회지)

Society of Preventive Korean Medicine (대한예방한의학회)
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Effect of Gongjindan-gamibang on the Pharmacokinetics Profiles of Sorafenib in Male SD Rats (2) - Single Oral Combination Treatment of Sorafenib 50mg/kg with Gongjindan-gamibang 100 mg/kg, 3.5hr-intervals with 7-day Repeated Treatment -

  • Lee, Chang Hyeong (Department of Internal Medicine, Daegu Catholic University Hospital) ;
  • Kim, Seung Mo (Department of Korean Internal Medicine of Hepatology, College of Korean Medicine, Daegu Haany University) ;
  • Kang, Su Jin (The Medical Research center for Globalization of Herbal Formulation, Daegu Haany University) ;
  • Park, Soo Jin (The Medical Research center for Globalization of Herbal Formulation, 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) ;
  • Lee, Young Joon (The Medical Research center for Globalization of Herbal Formulation, Daegu Haany University) ;
  • Ku, Sae Kwang (The Medical Research center for Globalization of Herbal Formulation, Daegu Haany University)
  • Received : 2015.01.29
  • Accepted : 2015.04.06
  • Published : 2015.04.30
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Abstract

Objective : In the previous study, co-administration of Gongjindan-gamibang (GJD) with sorafenib increased oral bioavailability of sorafenib through augment the absorption, therefore, the effects of GJD co-administration on the pharmacokinetics of sorafenib were observed after single and 7-day repeated oral co-administration with 3.5 hr-intervals in the present study. Method : After 50 mg/kg of sorafenib treatment, GJD 100 mg/kg was administered with 3.5 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 sorafenib 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 : GJD markedly inhibited the absorption of sorafenib, from 1 hr to 24 hrs after end of first 3.5 hr-interval co-administration, the $C_{max}$ (-43.27%), $AUC_{0-t}$ (-56.29%) and $AUC_{0-inf}$ (-66.70%) of sorafenib in co-administered rats were dramatically decreased as compared with sorafenib single treated rats. However, GJD significantly increased the absorption of sorafenib, from 4 hr to 8 hrs after end of last 7th 3.5 hr-interval co-administration, the $AUC_{0-t}$ (34.08%) and $AUC_{0-inf}$ (37.31%) of sorafenib in co-administered rats were dramatically increased as compared with sorafenib single treated rats. Conclusion : Although GJD decreased the oral bioavailability of sorafenib through inhibition of gastrointestinal absorptions after end of first 3.5 hr-interval co-administration, it is observed that GJD increases the oral bioavailability of sorafenib as facilitated the absorption after end of last 7th repeated co-administration. Hence, the co-administration of GJD and sorafenib should be avoided in the combination therapy of sorafenib with GJD on anticancer therapy.

Keywords

Acknowledgement

Supported by : Korea of Health & Welfare

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