Does H2 receptor antagonist-resistant ulcer exist?--A review based on bioavailability in man.

Recently the term H2 receptor antagonist-resistant (H2RA-resistant) ulcer has been used increasingly commonly, instead of the conventional term of intractable ulcer, to designate an ulcer which does not respond to treatment with an H2 receptor antagonist (H2RA). However, many authors report that an H2RA resistant ulcer can be cured by increasing the dosage of H2RA, or using another H2RA. In this study, the absorption and bioavailability of oral doses of each of three H2RAs, which are possible factors in these effects, were studied in healthy volunteers. The results showed that there was a great difference in bioavailability between cimetidine (80%), famotidine (39%) and ranitidine (50%). The lower bioavailability of famotidine and ranitidine may be partially explained by the following facts: 35.8% to 57.8% of orally administered famotidine is decomposed in gastric acid (pH 1) before absorption; and about 50% of ranitidine is metabolized in the liver before distribution (first-pass effect). Thus famotidine and ranitidine should be carefully administered to patients with slow gastric emptying and hepatic dysfunction, respectively. In general practice, many patients may not respond well to treatments because of their poor absorption, or extensive metabolism. In such cases, further effectiveness and safety could be expected if another H2RA, appropriately tailored to patients' conditions, were chosen. On the basis of these findings, it would seem premature to conclude that H2RA-resistant ulcer exists.