Human Jejunal Permeability of Two Polar Drugs: Cimetidine

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 ab-sorbed 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 signifi-cant 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 phenylal-anine, appear to be consistent with their less than complete absorp-tion in humans. KEY WORDS: intestinal permeability; drug absorption; cimetidine; ranitidine; biopharmaceutic classification system