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Pharmaceutical Research

, Volume 29, Issue 9, pp 2419–2431 | Cite as

Dynamic Analysis of GI Absorption and Hepatic Distribution Processes of Telmisartan in Rats Using Positron Emission Tomography

  • Makoto Kataoka
  • Tadayuki Takashima
  • Tomotaka Shingaki
  • Yoshinobu Hashidzume
  • Yumiko Katayama
  • Yasuhiro Wada
  • Hiroyuki Oh
  • Yoshie Masaoka
  • Shinji Sakuma
  • Yuichi Sugiyama
  • Shinji YamashitaEmail author
  • Yasuyoshi Watanabe
Research Paper

ABSTRACT

Purpose

To dynamically analyze the processes of oral absorption and hepatobiliary distribution of telmisartan using positron emission tomography (PET).

Methods

11C-labeled telmisartan ([11C]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 [11C]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.

Conclusion

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.

KEY WORDS

molecular imaging oral absorption positron emission tomography (PET) telmisartan transporter 

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Makoto Kataoka
    • 1
    • 2
  • Tadayuki Takashima
    • 1
  • Tomotaka Shingaki
    • 1
    • 3
  • Yoshinobu Hashidzume
    • 1
  • Yumiko Katayama
    • 1
  • Yasuhiro Wada
    • 1
  • Hiroyuki Oh
    • 2
  • Yoshie Masaoka
    • 2
  • Shinji Sakuma
    • 2
  • Yuichi Sugiyama
    • 4
  • Shinji Yamashita
    • 2
    Email author
  • Yasuyoshi Watanabe
    • 1
  1. 1.RIKEN Center for Molecular Imaging ScienceKobeJapan
  2. 2.Faculty of Pharmaceutical SciencesSetsunan UniversityHirakataJapan
  3. 3.ADME Research Inc.MinohJapan
  4. 4.Graduate School of Pharmaceutical SciencesThe University of TokyoBunkyo-kuJapan

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