title: Comparison of two approaches of intestinal absorption by puerarin.
abstract: BACKGROUND
  Everted gut sac (EGS) and in situ single-pass intestinal perfusion (SPIP) have been widely used in the study of drug absorption and biopharmaceutical classification systems (BCS). Furthermore, they could also be applied in the research of drug intestinal first-pass metabolism. Since most of Chinese herbal medicines (CHMs) are orally administrated, it is necessary to study the permeability of active ingredients of CHMs. Thus, we attempted to apply the EGS and SPIP models to study the permeability of puerarin, one of the active marker compounds (AMCs) of Puerariae Radix.
  
  
  METHODS
  In the present study, three rat models of ex vivo and in situ, EGS, SPIP, and in situ intestinal perfusion with venous sampling (IPVS), were established to determine the permeability coefficient of puerarin. The apparent permeability coefficient (Papp) was obtained by EGS. The SPIP model was used to determine the effective permeability coefficient (Peff) in different intestinal segments. The blood permeability coefficient (Pblood) was determined by IPVS. Puerarin concentration of perfusion and blood samples were measured by HPLC.
  
  
  RESULTS
  Puerarin could filter into EGS incubated in aqueous extract of Puerariae Radix or puerarin solution. In the SPIP experiment, the concentration effect on Peff was observed in the ileum, but not in the other three intestinal segments. The Pblood was 0.068±0.002×10(-5)cm/s and was 16-fold lower than the Peff (1.114±0.153×10(-5)cm/s) in the IPVS experiment at 80μg/mL puerarin. As expected, the Peff (1.24±0.11×10(-5)cm/s) in SPIP did not differ from the Peff in IPVS. The Papp was 0.199×10(-5)cm/s at 1200μg/mL puerarin, 10-fold lower than Peff (2.047±0.116×10(-5)cm/s) in SPIP.
  
  
  CONCLUSIONS
  Three models for permeability were successfully practiced in the study of puerarin absorption and our research strategy will be useful for herbal constituent absorption in the future.
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, PR China.
authors.forename: Hewei
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Dong
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, PR China. Electronic address: liuyang@bucm.edu.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Zhongcai Health (Beijing) Biological Technology Development Co., Ltd., Beijing, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, PR China. Electronic address: yjqiao@bucm.edu.cn.
authors.forename: Yanjiang
authors.initials: Y
authors.lastname: Qiao
mesh_terms: D000818:Animals; D004365:Drugs, Chinese Herbal / Q000378:metabolism; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007529:Isoflavones / Q000378:metabolism*; D008297:Male; D010477:Perfusion / Q000379:methods; D010539:Permeability; D029908:Pueraria; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004365:Drugs, Chinese Herbal; D007529:Isoflavones; C442842:plant extract, Puerariae Radix; C033607:puerarin
keywords: Everted gut sac; In situ intestinal perfusion with venous sampling; In situ single-pass intestinal perfusion; Methods; Puerarin