Human jejunal permeability of two polar drugs: Cimetidine and ranitidine

Purpose. To determine the human jejunal permeability of cimetidine and rani tidine using a regional jejunal perfusion approach, and to integrate such d eterminations with previous efforts to establish a baseline correlation bet ween permeability and fraction dose absorbed in humans for soluble drugs. Methods. A sterile multi-channel perfusion tube, Loc-I-Gut (R), was inserte d orally and positioned in the proximal region of the jejunum. A solution c ontaining cimetidine or ranitidine and phenylalanine, propranolol, PEG 400, and PEG 4000 was perfused through a 10 cm jejunal segment in 6 and 8 subje cts, 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 insign ificant. The mean permeabilities for propranolol, phenylalanine, and PEG 40 0 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 fo r a given marker were not significant between phases or between the two stu dies. Conclusions. The 10-fold lower permeabilities found for cimetidine and rani tidine in this study, compared to propranolol and phenylalanine, appear to be consistent with their less than complete absorption in humans.