Pharmacokinetics and pharmacodynamics of acid-suppressive agents in patients with gastroesophageal reflux disease.

Key pharmacokinetic and pharmacodynamic aspects of gastric acid-suppressive agents in patients with gastroesophageal reflux disease (GERD) are discussed. The acid-suppressive potencies of the histamine H2-receptor antagonists vary widely because of differences in clearance and other factors. The durations of action of cimetidine, ranitidine, and famotidine are similar to the dosage intervals usually chosen (6, 8, and 12 hours, respectively). Single bedtime doses of these drugs will effectively treat duodenal ulcer disease, but GERD requires a different approach since its symptoms are not well controlled by partial (less than 24-hour) suppression of gastric acid. One way to achieve greater efficacy in treating GERD is to administer higher doses more frequently. Another approach is to adjust the dosage upward until symptoms disappear. The improved acid-suppression characteristic of the proton-pump inhibitors was quickly applied to GERD therapy. Unlike the H2 antagonists, omeprazole completely suppresses circadian peaks in acid secretion, and omeprazole performs better than ranitidine in clinical trials. The use of omeprazole is limited, however, by concerns over secondary elevation of serum gastrin and the association between achlorhydria and gastric carcinoma in rats. Omeprazole may offer cost advantages over other agents. Because the effective dosages of all these agents vary, individualized dosage-adjustment strategies are necessary. Pharmacists can help to optimize treatment by monitoring pharmacodynamic markers. With a flexible approach to drug and dosage selection, it should be possible to manage GERD in most patients in a cost-effective manner.