title: Enhancement of absorption and bioavailability of echinacoside by verapamil or clove oil.
abstract: OBJECTIVE
  This present study investigated the absorption kinetics of echinacoside (ECH) in situ and in vitro and its oral bioavailability in rats. Additional aim was to find an agent(s) to promote ECH absorption and oral bioavailability among two efflux proteins and three absorption promoters.
  
  
  METHODS
  ECH absorption behaviors were investigated by everted gut sac model in vitro and single-pass intestinal perfusion model in situ. Pharmacokinetics study was performed to investigate the influences of verapamil and clove oil on ECH bioavailability in vivo. All samples were measured at different time intervals by high performance liquid chromatography.
  
  
  RESULTS
  The results showed that the effective permeability coefficient (P eff) and apparent permeability coefficient of ECH were 0.83×10(-6)-3.23×10(-6) cm/s and 2.99×10(-6)-9.86×10(-6) cm/s, respectively. The P eff among duodenum, jejunum, and ileum were not statistically different, but they were higher than colon (P<0.01), which demonstrated that intestinal ECH absorption was poor and site dependent. Additionally, verapamil and clove oil significantly increased the jejunal P eff of ECH both in situ and in vitro. Moreover, the bioavailability of ECH in combination with verapamil and clove oil were increased by 1.37-fold (P<0.05) and 2.36-fold (P<0.001), respectively, when compared to ECH group. Overall, verapamil and clove oil facilitated ECH absorption and oral bioavailability.
  
  
  CONCLUSIONS
  The absorption and bioavailability of ECH were enhanced by verapamil and clove oil, respectively, both in vitro and in vivo. Consequently, the combination of verapamil and clove oil with ECH will be a promising and effective approach to promote intestinal absorption and oral bioavailability of ECH.
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors: Jin-Yang
authors: JY
authors: Shen
authors: Key Laboratory of Pharmaceutical and Biological Marine Resources Research and Development of Jiangsu Province, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
authors: Xiao-Lin
authors: XL
authors: Yang
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors: Zhong-Lin
authors: ZL
authors: Yang
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors: Jun-Ping
authors: JP
authors: Kou
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors: Fei
authors: F
authors: Li
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D045783:Clove Oil / Q000494:pharmacology*; D006027:Glycosides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008297:Male; D008954:Models, Biological; D010539:Permeability; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D045783:Clove Oil; D006027:Glycosides; D014700:Verapamil; C060297:echinacoside
keywords: absorption promoter; efflux protein inhibitor; intestinal absorption