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Human jejunal permeability of two polar drugs: Cimetidine and ranitidine

Authors
Takamatsu, NKim, ONWelage, LSIdkaidek, NMHayashi, YBarnett, JYamamoto, RLipka, ELennernas, HHussain, ALesko, LAmidon, GL
Issue Date
Jun-2001
Publisher
KLUWER ACADEMIC/PLENUM PUBL
Keywords
intestinal permeability; drug absorption; cimetidine; ranitidine; biopharmaceutic classification system
Citation
PHARMACEUTICAL RESEARCH, v.18, no.6, pp.742 - 744
Journal Title
PHARMACEUTICAL RESEARCH
Volume
18
Number
6
Start Page
742
End Page
744
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/16654
DOI
10.1023/A:1011020025338
ISSN
0724-8741
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 (R), 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) x 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) x 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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