· .. beta blockers, ... Cytochrome P-4S0 is involved in the metabolic

oxidation of lipophilic compounds , including some beta blockers ; therefore , the concurrent administration of cimetidine and, to a lesser extent , ranit idine may reduce hepatic el imination of those compounds . Many beta blockers undergo substantial first -pass metabolism and H2-

antagonists have the potential to increase oral bioavailability of these drugs when administered concurrently.

Such effects on oral bioavailability of beta blockers have been detected in many studies . Some investigators have postulated a reduct ion in hepatic blood flow , but the use of electromagnetic techniques in animal studies indicated that a cimetidine-induced decrease in hepatic blood flow does not occur. A correlation between extent of oxidative metabolism of different beta blockers and the degree of interaction with cimetidine support cytochrome P-4S0 inhibition as the mechanism of interaction . Significant interaction occurs between cimetidine and beta blockers , but in a majority of studies with ranitidine , the degree of interaction was not significant.

Beta blockers have high therapeutic Indices and show high intrapatient variation , and the correlation between serum concentration and pharmacodynamic effect is not strong. Therefore , for a drug interaction to be clinically significant , a large change in serum concentration must occur . In an overwhelming majority of studies , neither cimetidine nor ranitidine enhanced the action of any of a number of beta blockers in healthy volunteers .

On ly 2 case reports of possible drug interactions between cimetidine and beta blockers have been published, despite intensive postmarketing surveillance, further emphasising the minimal clinical importance of this interaction in patients as well as in healthy volunteers . In 1 case , a patient receiving cimetidine was given a beta blocker and had a 340% increase in propranolol AUC after an 80mg dose, but no adverse effects were experienced . In the second case a number of complicating factors were involved and the role of a drug interaction between cimetidine and labetalol was uncertain . In conclusion , there appears to be a significant effect of cimetidine on the pharmacokinetics of beta blockers , but this is not reflected in a significant clinical effect. Beta blocker therapy should be titrated and individualised as usual , but concurrent H2-antagonist therapy does not necessitate any special adjustment. Sax MJ AnalysIs of possible drug Inleracllons belween clmelldlne (and ranltldlne) and Ii blockers Advances In Therapy 5 210·228 Sep 1988 149 references I H,'