title: Study on intestinal absorption and pharmacokinetic characterization of diester diterpenoid alkaloids in precipitation derived from fuzi-gancao herb-pair decoction for its potential interaction mechanism investigation.
abstract: BACKGROUND
  Aconitum carmichaelii Debx. (Fuzi in Chinese) has been widely clinically used to treat heart failure and rheumatism. Whereas its serious toxicity, Radix et Rhizoma Glycyrrhizae (Gancao in Chinese) was combined with it as traditional Chinese medicine (TCM) herb-pair for toxicity reduction and pharmacological effect improvement. Though some previous viewpoints about that has been reported, the underlying interaction mechanism of two herbs remain unknown and definitely worthy of investigating.
  
  
  OBJECTIVE
  In present study, we focus on Fuzi-Gancao herb-pair precipitation (FGP), considering it related to the compatibility mechanism of Fuzi-Gancao herb-pair. The intestinal absorption and pharmacokinetic characters of 3 diester diterpenoid alkaloids in the precipitation were investigated.
  
  
  METHODS
  Both everted gut sac model and in situ single-pass intestinal perfusion model were used to investigate rat small intestinal permeability and transport mechanism of aconitine, hypaconitine and mesaconitine. Moreover, by means of determination of the plasma concentration, the pharmacokinetic characters of 3 alkaloid compounds in rats have been developed.
  
  
  RESULTS
  In everted gut sac permeability experiment, the permeability of hypaconitine appeared best in ileum. Furthermore, their uptakes were increased in the presence of P-glycoprotein (P-gp) inhibitors. In situ single-pass intestinal perfusion uptake experiment, results revealed that the transport mechanism may fit the active transport mechanism. And 3 alkaloids in FPG could be absorbed well in rats, fitting 2-compartment model with 1(st) order absorption and lag time.
  
  
  CONCLUSIONS
  Our results in present study indicated that 3 diester diterpenoid alkaloids in FGP could be dissolved out in gastrointestinal tract firstly and then absorbed in blood after oral administration, which could result in prolonging their mean residence time and adding their absorbed doses, avoiding dose dumping. The current study has significant enlightenments for further investigation on the interaction mechanisms of other acid-base herb-pairs as well as Fuzi-Gancao herb-pair.
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, Wenjiang District 1166, Chengdu City, Sichuan, PR China.
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Zhang
authors.forename: Wan
authors.initials: W
authors.lastname: Liao
authors.forename: Yu-xin
authors.initials: YX
authors.lastname: He
authors.forename: Yao
authors.initials: Y
authors.lastname: He
authors.forename: Dong
authors.initials: D
authors.lastname: Yan
authors.forename: Chao-Mei
authors.initials: CM
authors.lastname: Fu
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D031841:Aconitum / Q000737:chemistry; D000284:Administration, Oral; D000470:Alkaloids / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport; D011232:Chemical Precipitation; D004224:Diterpenes / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics*; D004952:Esters / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D008516:Medicine, Chinese Traditional; D008954:Models, Biological; D010477:Perfusion; D008517:Phytotherapy; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000470:Alkaloids; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D004952:Esters; C058309:hypaconitine; C019470:mesaconitine; D000157:Aconitine