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Human Jejunal Permeability of Two Polar Drugs: Cimetidine and Ranitidine

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Abstract

Purpose. To determine the human jejunal permeability of cimetidine and ranitidine using a regional jejunal perfusion approach, and to integrate such determinations with previous efforts to establish a baseline correlation between permeability and fraction dose absorbed in humans for soluble drugs.

Methods. A sterile multi-channel perfusion tube, Loc-I-Gut®, was inserted orally and positioned in the proximal region of the jejunum. A solution containing cimetidine or ranitidine and phenylalanine, propranolol, PEG 400, and PEG 4000 was perfused through a 10 cm jejunal segment in 6 and 8 subjects, respectively.

Results. The mean Peff (± se) of cimetidine and ranitidine averaged over both phases were 0.30 (0.045) and 0.27 (0.062) × 10−4cm/s, respectively, and the differences between the two were found to be statistically insignificant. The mean permeabilities for propranolol, phenylalanine, and PEG 400 averaged over both phases and studies were 3.88 (0.72), 3.36 (0.50), and 0.56 (0.08) × 10−4 cm/s, respectively. The differences in permeability for a given marker were not significant between phases or between the two studies.

Conclusions. The 10-fold lower permeabilities found for cimetidine and ranitidine in this study, compared to propranolol and phenylalanine, appear to be consistent with their less than complete absorption in humans.

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Authors and Affiliations

  1. Yamanouchi Pharmaceutical Co. Ltd., Shizuoka, Japan

    Narushi Takamatsu

  2. Sookmyung Women' University, Seoul, 140-742, Korea

    Ok-Nam Kim

  3. College of Pharmacy, The University of Michigan, USA

    Lynda S. Welage

  4. Pharmacy Services, University Hospital, Ann Arbor, Michigan, 48109

    Lynda S. Welage

  5. Jordan University of Science and Technology, Irbid, Jordan

    Nasir M. Idkaidek

  6. Nagoya City University, Aichi, Japan

    Yayoi Hayashi

  7. Medical School, The University of Michigan, Ann Arbor, Michigan

    Jeffrey Barnett

  8. Ono Pharmaceutical Co. Ltd., c, Osaka, Japan, 618

    Ryuzo Yamamoto

  9. Pfizer Global R&D, Ann Arbor, Michigan, 48105

    Elke Lipka

  10. School of Pharmacy, Uppsala University, Uppsala, Sweden

    Hans Lennernäs

  11. Office of Clinical Pharmacology and Biopharmaceutics, CDER, FDA, Rockville, Maryland, 20852

    Ajaz Hussain

  12. Office of Research Resources, CDER, FDA, Rockville, Maryland, 20852

    Lawrence Lesko & Gordon L. Amidon

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  1. Narushi Takamatsu
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  2. Ok-Nam Kim
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  3. Lynda S. Welage
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  4. Nasir M. Idkaidek
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  5. Yayoi Hayashi
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  6. Jeffrey Barnett
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  7. Ryuzo Yamamoto
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  8. Elke Lipka
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  9. Hans Lennernäs
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  10. Ajaz Hussain
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  11. Lawrence Lesko
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  12. Gordon L. Amidon
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This manuscript represents the personal opinions of the author and does not necessarily represent the views or policies of the agency

This manuscript represents the personal opinions of the author and does not necessarily represent the views or policies of the agency

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Takamatsu, N., Kim, ON., Welage, L.S. et al. Human Jejunal Permeability of Two Polar Drugs: Cimetidine and Ranitidine. Pharm Res 18, 742–744 (2001). https://doi.org/10.1023/A:1011020025338

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  • DOI: https://doi.org/10.1023/A:1011020025338

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