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
| Autor: | Tomoko Morisaki, Kyoko Takahashi, Xiao-Long Hou, Koichi Takahashi |
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| Rok vydání: | 2013 |
| Předmět: |
Male
CYP3A Pharmaceutical Science Administration Oral Pharmacology Models Biological Intestinal absorption chemistry.chemical_compound Pharmacokinetics Microsomes Animals Cytochrome P-450 CYP3A Humans Intestinal Mucosa Rats Wistar Biotransformation Flavonoids In vitro Baicalein Body Fluids Rats Intestines chemistry Intestinal Absorption Caco-2 Flavanones Microsome Cytochrome P-450 CYP3A Inhibitors Caco-2 Cells Baicalin |
| Zdroj: | The Journal of pharmacy and pharmacology. 65(10) |
| ISSN: | 2042-7158 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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