title: [Oral bioavailability and intestinal disposition of dehydroandrographolide in rats].
abstract: OBJECTIVE
  Dehydroandrographolide (DP) from Andrographis paniculata (Burm. F.) Nees is a potential anticancer agent. This study aimed to investigate the oral bioavailability and intestinal disposition of DP to provide useful information for the development of DP as a new candidate anticancer drug.
  
  
  METHODS
  The pharmacokinetics of DP was evaluated in rats, and its intestinal disposition was determined using cultured Caco-2 cells and a single-pass rat intestinal perfusion model.
  
  
  RESULTS
  The oral bioavailability of DP was 11.92% in rats. The apparent permeability coefficient (P(app)) of DP from the basolateral side (B) to the apical side (A) (5.37×10(-5) cm/s) of the Caco-2 model was roughly equal to that from A to B (4.56×10(-5) cm/s), suggesting no involvement of the efflux transporter(s). In the perfusion model, no significant difference was found in the effective permeability (P*(eff)) of DP between the 4 segments of the intestine. No significant metabolism of DP was detected in the intestinal perfusates. The amount of DP found in the bile was only about 0.1% of the absorbed amount. The P*(eff) and bile amounts of DP were not significantly increased by P-glycoprotein (P-gp) inhibitor or breast cancer resistant protein (BCRP) inhibitor (P>0.05).
  
  
  CONCLUSIONS
  The bioavailability of DP was 11.92% in rats. DP has good absorption and metabolism stability in the intestine. The efflux transporters such as P-gp and BCRP do not participate in DP transport.
authors.affiliation: Department of Pharmaceutics, Southern Medical University, Guangzhou, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Ye
authors.forename: Fugui
authors.initials: F
authors.lastname: Liang
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Shi
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport; D018938:Caco-2 Cells; D004224:Diterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004224:Diterpenes; C478098:dehydroandrographolide