Human jejunal permeability of two polar drugs: Cimetidine and ranitidine

Narushi Takamatsu; Ok Nam Kim; Lynda S. Welage; Nasir M. Idkaidek; Yayoi Hayashi; Jeffrey Barnett; Ryuzo Yamamoto; Elke Lipka; Hans Lennernäs; Ajaz Hussain; Lawrence Lesko; Gordon L. Amidon

doi:10.1023/A:1011020025338

Human jejunal permeability of two polar drugs: Cimetidine and ranitidine

Narushi Takamatsu, Ok Nam Kim, Lynda S. Welage, Nasir M. Idkaidek, Yayoi Hayashi, Jeffrey Barnett, Ryuzo Yamamoto, Elke Lipka, Hans Lennernäs, Ajaz Hussain, Lawrence Lesko, Gordon L. Amidon

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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 P_eff (± se) of cimetidine and ranitidine averaged over both phases were 0.30 (0.045) and 0.27 (0.062) × 10^-4 cm/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.

Original language	English (US)
Pages (from-to)	742-744
Number of pages	3
Journal	Pharmaceutical research
Volume	18
Issue number	6
DOIs	https://doi.org/10.1023/A:1011020025338
State	Published - 2001

Bibliographical note

Funding Information:
This work was supported in part by FDA, Grant FD014, and the General Clinical Research Center (GCRC) of the University of Michigan, NIH M01RR00042. Ok-Nam Kim was supported in part by a grant from the Korean Government and Nasir M. Idiadek was supported in part by a grant from Jordan University of Science and Technology. The valuable assistance of John Wlodyga and the staff of the GCRC are gratefully acknowledged.

Keywords

Biopharmaceutic classification system
Cimetidine
Drug absorption
Intestinal permeability
Ranitidine

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title = "Human jejunal permeability of two polar drugs: Cimetidine and ranitidine",

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{\textregistered}, 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) × 10-4 cm/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.",

keywords = "Biopharmaceutic classification system, Cimetidine, Drug absorption, Intestinal permeability, Ranitidine",

author = "Narushi Takamatsu and Kim, {Ok Nam} and Welage, {Lynda S.} and Idkaidek, {Nasir M.} and Yayoi Hayashi and Jeffrey Barnett and Ryuzo Yamamoto and Elke Lipka and Hans Lennern{\"a}s and Ajaz Hussain and Lawrence Lesko and Amidon, {Gordon L.}",

note = "Funding Information: This work was supported in part by FDA, Grant FD014, and the General Clinical Research Center (GCRC) of the University of Michigan, NIH M01RR00042. Ok-Nam Kim was supported in part by a grant from the Korean Government and Nasir M. Idiadek was supported in part by a grant from Jordan University of Science and Technology. The valuable assistance of John Wlodyga and the staff of the GCRC are gratefully acknowledged.",

year = "2001",

doi = "10.1023/A:1011020025338",

language = "English (US)",

volume = "18",

pages = "742--744",

journal = "Pharmaceutical research",

issn = "0724-8741",

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TY - JOUR

T1 - Human jejunal permeability of two polar drugs

T2 - Cimetidine and ranitidine

AU - Takamatsu, Narushi

AU - Kim, Ok Nam

AU - Welage, Lynda S.

AU - Idkaidek, Nasir M.

AU - Hayashi, Yayoi

AU - Barnett, Jeffrey

AU - Yamamoto, Ryuzo

AU - Lipka, Elke

AU - Lennernäs, Hans

AU - Hussain, Ajaz

AU - Lesko, Lawrence

AU - Amidon, Gordon L.

N1 - Funding Information: This work was supported in part by FDA, Grant FD014, and the General Clinical Research Center (GCRC) of the University of Michigan, NIH M01RR00042. Ok-Nam Kim was supported in part by a grant from the Korean Government and Nasir M. Idiadek was supported in part by a grant from Jordan University of Science and Technology. The valuable assistance of John Wlodyga and the staff of the GCRC are gratefully acknowledged.

PY - 2001

Y1 - 2001

N2 - 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) × 10-4 cm/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.

AB - 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) × 10-4 cm/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.

KW - Biopharmaceutic classification system

KW - Cimetidine

KW - Drug absorption

KW - Intestinal permeability

KW - Ranitidine

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DO - 10.1023/A:1011020025338

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AN - SCOPUS:0034871945

SN - 0724-8741

VL - 18

SP - 742

EP - 744

JO - Pharmaceutical research

JF - Pharmaceutical research

IS - 6

ER -

Human jejunal permeability of two polar drugs: Cimetidine and ranitidine

Abstract

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Keywords

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