title: Dynamic analysis of GI absorption and hepatic distribution processes of telmisartan in rats using positron emission tomography.
abstract: OBJECTIVE
  To dynamically analyze the processes of oral absorption and hepatobiliary distribution of telmisartan using positron emission tomography (PET).
  
  
  METHODS
  (11)C-labeled telmisartan ([(11)C]TEL) was orally administered to rats with or without non-radiolabeled telmisartan (0.5, and 10 mg/kg). PET scanning of abdominal region and whole body was performed under conscious condition. In situ intestinal closed loop study in rats and in vitro permeation study in MDR1-MDCK II cell monolayers were also conducted.
  
  
  RESULTS
  After oral administration of [(11)C]TEL, systemic bioavailability and hepatic distribution of radioactivity increased non-linearly with dose. In the intestinal lumen, both telmisartan and its glucuronide were detected and the ratio of telmisartan decreased dramatically at high dose of telmisartan. In situ closed loop study showed most of telmisartan-glucuronide detected in the intestinal lumen was derived from the bile excretion. In addition, in vitro permeation study revealed that telmisartan is a substrate of P-glycoprotein.
  
  
  CONCLUSIONS
  PET imaging analysis successfully demonstrated the processes of intestinal absorption and hepatic distribution of telmisartan. PET study combined with appropriate in situ and in vitro experiments is highly expected to be a potent tool for better understanding of GI absorption and subsequent tissue distribution of various drugs and drug candidates.
authors.affiliation: RIKEN Center for Molecular Imaging Science, 6-7-3 Minatojima minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kataoka
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Takashima
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Shingaki
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Hashidzume
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Katayama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Oh
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Masaoka
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakuma
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamashita
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000493:pharmacokinetics*; D001565:Benzoates / Q000493:pharmacokinetics*; D001682:Biological Availability; D041981:Gastrointestinal Tract / Q000378:metabolism*; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism*; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077333:Telmisartan
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D000077333:Telmisartan