Failure of ranitidine to interact with propranolol.

Failure of ranitidine to interact with propranolol The histamine H2-receptor antagonist ranitidine has recently been introduced into clinical practice for the treatment of peptic ulcer. Its therapeutic effects appear similar to those of cimetidine, but early reports suggest that it does not affect hepatic drug metabolism.' 2 This probably reflects a change in chemical structure, in that the central imidazole ring has been replaced by a furan ring and the side-chain has been modified. It has been suggested that the imidazole ring facilitates binding of cimetidine to microsomal cytochrome P450,3 which possibly explains the reduction in hepatic extraction of propranolol. It seems likely therefore that this would not be seen with ranitidine and we undertook a study to assess the effect of ranitidine on propranolol. We studied six healthy volunteers (five men and one woman; average age 41 years, range 22-71). Two had taken part in a previous study of the interaction between cimetidine and propranolol.4 All were non-smokers and had no evidence of respiratory, cardiovascular, renal, or thyroid disease. All gave informed consent and local ethical committee approval was obtained for the study. During the study no other drugs were allowed. After an overnight fast 80 mg propranolol was given orally and 5 ml samples of venous blood were taken at 0, 30, 60, 90, 120, 240, 360, 480, and 720 minutes for estimating propranolol concentration. The study was repeated after a two-week course of ranitidine, 150 mg orally twice daily; during this course a separate 10 ml blood sample was taken for measuring plasma ranitidine concentrations, thereby ensuring compliance. After three weeks with no treatment four subjects took cimetidine 200 mg orally three times daily and 400 mg at night for two weeks, after which the study was repeated again. The other two subjects had taken cimetidine in a previous study.4 All blood samples were stored at-20°C until assayed. Whole-blood propranolol concentrations were estimated using the fluorometric method previously described.4 The areas under the blood concentration time curves for propranolol with and without ranitidine were measured using a planimeter, andthe values were used as a measure of the relative bioavailability of the drug. Data on ranitidine, cimetidine, and no treatment were compared using Student's t test for paired data. The figure shows mean blood propranolol concentrations with and without treatment. The data on cimetidine are included for comparison only as similar data have been reported previously.4 There was …