Absorption barriers in the rat intestinal mucosa: 1. application of an in situ perfusion model to simultaneously assess drug permeation and metabolism

✍ Scribed by Daniel R. Mudra; Ronald T. Borchardt

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 457 KB
• Volume: 99
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.21912

✦ Synopsis

Modulation of intestinal drug absorption barriers can have a profound impact on the bioavailability of orally administered compounds. With its commonality of use as an absorption model, it is valuable to assess the role of such barriers in the rat intestinal mucosa. In the present study, atenolol and verapamil were concomitantly delivered in the in situ perfused rat intestine in the presence or absence of inhibitors to simultaneously assess the function and modulation of passive diffusion barriers, cytochrome P450 (CYP)3A metabolism and P-glycoprotein (P-gp) efflux. A high performance liquid chromatography-tandem mass spectrometry method measured atenolol, verapamil and the CYP3A-mediated metabolite, norverapamil, with linearity (r(2) > 0.99), precision (CV