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

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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.

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Authors and Affiliations

  1. RIKEN Center for Molecular Imaging Science, 6-7-3 Minatojima minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan

    Makoto Kataoka, Tadayuki Takashima, Tomotaka Shingaki, Yoshinobu Hashidzume, Yumiko Katayama, Yasuhiro Wada & Yasuyoshi Watanabe

  2. Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka, 573-0101, Japan

    Makoto Kataoka, Hiroyuki Oh, Yoshie Masaoka, Shinji Sakuma & Shinji Yamashita

  3. ADME Research Inc., 1-12-8 Senba-higashi, Minoh, Osaka, 562-0035, Japan

    Tomotaka Shingaki

  4. Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Yuichi Sugiyama

Authors
  1. Makoto Kataoka
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  2. Tadayuki Takashima
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  3. Tomotaka Shingaki
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  4. Yoshinobu Hashidzume
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  5. Yumiko Katayama
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  6. Yasuhiro Wada
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  7. Hiroyuki Oh
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  8. Yoshie Masaoka
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  9. Shinji Sakuma
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  10. Yuichi Sugiyama
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  11. Shinji Yamashita
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  12. Yasuyoshi Watanabe
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Corresponding author

Correspondence to Shinji Yamashita.

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Kataoka, M., Takashima, T., Shingaki, T. et al. Dynamic Analysis of GI Absorption and Hepatic Distribution Processes of Telmisartan in Rats Using Positron Emission Tomography. Pharm Res 29, 2419–2431 (2012). https://doi.org/10.1007/s11095-012-0768-7

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  • DOI: https://doi.org/10.1007/s11095-012-0768-7

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