The inhibitory effects of ranitidine and cimetidine on propranolol elimination by the rat isolated perfused liver.

The effect of low (50 micrograms) and high (1 mg) doses of the histamine H2-receptor antagonists cimetidine and ranitidine on the first pass extraction of propranolol was studied in the rat isolated perfused liver. Both low and high dose cimetidine increased the area under the perfusate propranolol concentration time curve (AUC) 4 to 5-fold. Although low dose ranitidine did not alter propranolol AUC, high dose ranitidine increased it to the same extent as cimetidine. These results indicate that ranitidine has a clear propensity for microsomal inhibition, but one which is unlikely to be manifest at therapeutic dosage.