The effectiveness of ranitidine in reducing gastric acid-secretion decreases with continued therapy

To examine whether changes in inhibition of gastric acid secretion occur during chronic ranitidine therapy, duodenal ulcer patients in remission were studied before and after 9 months of maintenance ranitidine therapy (150 mg nocte). At each time, the effect of a bolus i.v. dose of ranitidine (50 mg) on pentagastrin-stimulated maximal acid output was measured. Oral and intravenous pharmacokinetic studies were also performed to examine whether changes in absorption or disposition occur during long-term dosage. After 9 months' therapy, ranitidine inhibited pentagastrin-stimulated secretion by a median of 62%, substantially less than the median inhibition of 95% pre-treatment. Median acid output in the period 60-120 min post-ranitidine was six times the pretreatment value. Since pharmacokinetic parameters were unaltered, this reduced ability to inhibit acid output appears to indicate reduced sensitivity of acid secreting mechanisms to ranitidine after prolonged dosage.