title: Baicalin pharmacokinetic profile of absorption process using novel in-vitro model: cytochrome P450 3A4-induced Caco-2 cell monolayers combined with rat intestinal rinse fluids.
abstract: OBJECTIVE
  This study was designed to investigate baicalin (BG) pharmacokinetic profile in absorption process using a new model and evaluate the potentiality as a new model.
  
  
  METHODS
  The effects of BG on intestinal cytochrome P450 3A4 (CYP3A) protein/mRNA expression, activity and permeability glycoprotein (P-gp) were evaluated in CYP3A4-induced Caco-2 cell monolayers or rats. Intestinal rinse fluids (IF) were obtained from rat were added to modified Caco-2 monolayers.
  
  
  RESULTS
  Orally administered BG (7 days pretreatment) inhibited intestinal CYP3A activity and protein expression. Baicalein (B) converted from BG by IF was detected in the upper jejunum in a portion-dependent manner. Subsequently, most BG were converted to B in the caecum. In modified Caco-2 monolayers, BG exhibited no effect on CYP3A4 activity or mRNA, whereas B and BG treated with IF inhibited CYP3A4 transcription and activity.
  
  
  CONCLUSIONS
  Intestinal CYP3A was inhibited following oral administration of BG to rat. Correspondingly, BG-mediated CYP3A inhibition was shown in vitro using modified Caco-2 monolayers treated with IF. Hence, in-vivo intestinal absorption pharmacokinetic was reproduced in vitro. IF is a key determinant of intestinal absorption, and it facilitated inhibition of CYP3A by B, not BG.
authors.affiliation: Department of Applied Pharmacognosy, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Morisaki
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Hou
authors.forename: Kyoko
authors.initials: K
authors.lastname: Takahashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D001826:Body Fluids; D018938:Caco-2 Cells; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D065692:Cytochrome P-450 CYP3A Inhibitors; D044950:Flavanones / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D044950:Flavanones; D005419:Flavonoids; C038044:baicalin; C006680:baicalein; D051544:Cytochrome P-450 CYP3A
keywords: absorption; baicalein; baicalin; cytochrome P450 3A4; intestinal bacteria