A study of intestinal absorption of bicyclol in rats: Active efflux transport and metabolism as causes of its poor bioavailability

18Citations
Citations of this article
21Readers
Mendeley users who have this article in their library.

Abstract

Purpose. To determine the possible mechanism of poor bioavailability of bicyclol, and clarify the respective contribution of P- glycoprotein (P-gp) and Cytochrome 3A (CYP3A). Methods. Rat in situ single-pass intestinal perfusion and Caco-2 cell monolayer model with selective inhibitors of CYP3A and P-gp were employed. Results. In rat intestinal perfusion, bicyclol (50μM) appearance in mesenteric blood (Pblood) was increased 3, 12 and 16-fold after addition of inhibitors of P-gp (LSN335984), CYP3A (troleandomycin, TAO) or P-gp and CYP3A (Cyclosporin A, CsA), respectively, whereas permeability of midazolam (CYP3A substrate only) was unchanged after addition of LSN335984 and increased 5 fold after addition of TAO. Moreover, the cumulative amount of bicyclol in mesenteric blood was increased at concentration range 10-100μM of bicyclol in perfusate. The basolateral to apical permeability value of bicyclol in Caco-2 monolayer was significantly deceased by LSN335984 and CsA. Conclusions. The poor bioavailability of bicyclol is mostly due to P-gp mediated efflux and metabolism by CYP3A in intestine, with CYP3A making more contribution than P-gp.

Cite

CITATION STYLE

APA

Tan, W., Chen, H., Zhao, J., Hu, J., & Li, Y. (2008). A study of intestinal absorption of bicyclol in rats: Active efflux transport and metabolism as causes of its poor bioavailability. Journal of Pharmacy and Pharmaceutical Sciences, 11(3), 97–105. https://doi.org/10.18433/j3b88v

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free