2012 Volume 132 Issue 8 Pages 911-917
Positron emission tomography (PET) is a powerful and noninvasive technology for molecular imaging in living systems. Its high sensitivity and high spatial-temporal resolution make this technology particularly useful to analyze the disposition of drugs in the body. PET technology could be applied to analyze the process of distribution of orally administered drugs on the basis of time-profiles of radioactivity in vivo. Kinetic analysis of radioactivity derived from 18F-labeled 2-fluoro-2-deoxy-D-glucose administered orally to rats under several conditions indicated that not only gastric emptying and intestinal transit but also the rate constant of intestinal absorption and limited process of oral absorption could be evaluated quantitatively. After oral administration of 11C-labeled telmisartan with or without non-radiolabeled telmisartan, systemic bioavailability and hepatic distribution of radioactivity significantly increased non-linearly with dose. In the intestinal lumen, telmisartan and its glucuronide, converted by UDP-glucuronosyl transferase (UGT), were detected and the ratio of telmisartan decreased at a high dose of telmisartan. In vitro permeation study revealed that telmisartan is a substrate of P-glycoprotein (P-gp). It was reported that hepatic uptake of telmisartan is mediated by organic anion transporting polypeptide 1B3 (OATP1B3) and most of the hepatic radioactivity in the liver is derived from telmisartan. These results indicated that P-gp for intestinal absorption, OATP1B3 for hepatic uptake and UGT for glucuronidation could be considered as limiting steps of orally administered telmisartan. Therefore, PET study is highly anticipated to be a potent tool for better understanding of gastrointestinal absorption and the subsequent tissue distribution of various drugs and candidates.
