Possible involvement of multiple P-glycoprotein-mediated efflux systems in the transport of verapamil and other organic cations across rat intestine

Pharm Res. 1995 Sep;12(9):1304-10. doi: 10.1023/a:1016217505990.


Purpose: We investigated the intestinal transport of verapamil, chlorpromazine, and propantheline, particularly their P-glycoprotein-mediated secretion.

Methods: Permeation of rat intestinal segments in vitro was determined using diffusion cells.

Results: Verapamil permeation in the serosal-to-mucosal direction was much greater than in the mucosal-to-serosal direction using duodenal, jejunal, and colonic membranes. The concentration dependence of jejunal permeation in the absorptive and secretory directions was consistent with saturability of a secretory transport system. Using a monoclonal antibody to inhibit P-glycoprotein-mediated secretion caused a significant enhancement of verapamil absorption through the jejunum. In contrast, the rat ileum did not preferentially transport verapamil in the secretory direction, and the P-glycoprotein antibody had no effect on ileal absorption. Chlorpromazine and propantheline enhanced the mucosal-to-serosal permeation of verapamil through the jejunum, most likely due to competitive inhibition of the P-glycoprotein-mediated secretory process. Vinblastine, tetraethylammonium, and guanidine did not affect verapamil permeation. Propantheline was also a substrate for P-glycoprotein-mediated secretory transport, but in contrast to verapamil, propantheline secretory transport was expressed in rat ileum.

Conclusions: These results suggest that these cationic compounds are transported by plural P-glycoprotein-mediated efflux systems with different substrate specificities depending on the intestinal site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Bile Acids and Salts / metabolism
  • Biological Transport, Active / drug effects
  • Cefazolin / pharmacokinetics
  • Chlorpromazine / pharmacokinetics
  • Chlorpromazine / pharmacology
  • Ileum / drug effects
  • Ileum / metabolism
  • In Vitro Techniques
  • Intestinal Absorption
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism*
  • Intestines / drug effects
  • Jejunum / drug effects
  • Jejunum / metabolism
  • Male
  • Propantheline / pharmacokinetics
  • Propantheline / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Theophylline / pharmacokinetics
  • Verapamil / pharmacokinetics*


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Bile Acids and Salts
  • Propantheline
  • Theophylline
  • Verapamil
  • Cefazolin
  • Chlorpromazine