Clinical study on the pathophysiology and treatment of PPI-resistant ulcers.

We studied the gastric acidity, gastric emptying, and proton pump inhibitor (PPI) plasma levels in 10 patients with PPI-resistant ulcers. The pH3 holding-time ratio was low in nine of these patients, with an average ratio of only 39%. PPI plasma levels in those patients were also much lower than in those with nonresistant ulcers. Gastric emptying, determined by the acetaminophen method, was reduced in all 10 patients. Therefore, PPI-resistant ulcers appear to result from insufficient inhibition of gastric acidity, with reduced gastric emptying interfering with the absorption of PPIs. In patients with mild reductions in gastric emptying, PPI plasma levels increased after a change from single-unit enteric-coated tablets (omeprazole) to multiunit enteric-coated granules in capsules (lansoprazole). This change in formulation markedly inhibited gastric acidity and led to rapid healing. In patients with moderate reductions in gastric emptying, doubling the dose of lansoprazole was effective. In patients with severely reduced gastric emptying, there appeared to be a limit to the effectiveness of oral administration of PPIs. Changing the formulation and doubling the dose to compensate for reduced gastric emptying are effective approaches in the treatment of patients with PPI-resistant ulcers.