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.

OBJECTIVES

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.

KEY FINDINGS

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.