Pharmacologic basis of pantoprazole dosing

Objective: This paper reviews the pharmacological properties of the proton pump inhibitor (PPI) pantoprazole, with a focus on the relationship between pantoprazole dosage and acid suppression in patients with gastroesophageal reflux disease (GERD), Background: Pantoprazole is a new PPI available in both oral and intravenou s (IV) formulations. Like other PPIs, pantoprazole is efficacious in the tr eatment of GERD and other acid-related diseases. It has high specificity fo r the relevant binding sites on activated proton pumps, and its profile of pH activation suggests that its activated cationic sulfenamide derivative s hould reach much higher concentrations at the site of acid production on th e parietal cell than elsewhere in the body. These features suggest that pan toprazole will act specifically on parietal cells, with little propensity t o cause unwanted systemic effects. Pantoprazole has minimal interaction wit h the cytochrome P-450 enzymes and no known drug interactions, suggesting t hat no dosage adjustment will be needed when it is taken concurrently with other medications that are metabolized by the cytochrome P-450 system. Its bioavailability is unaffected by food intake. Pantoprazole follows linear p harmacokinetics; studies indicate a linear dose response increasing up to 4 0 mg once daily, with some additional benefit at higher dosages for patient s with chronic hypersecretory conditions. The recommended dosage of pantopr azole in GERD is 40 mg once daily, This dosage suppresses intragastric pH t hroughout the day and some of the night, providing relief of nighttime gast roesophageal reflux, Both the oral and IV formulations of pantoprazole can be dosed at 40 mg once daily for patients with GERD, and apparent dose equi valence makes it possible to switch a patient from IV to oral pantoprazole without a change in dosage or loss of efficacy in either acid suppression o r disease healing. Dosage adjustments are rarely needed for special situati ons such as severe ulcer disease. No dosage adjustment is necessary in elde rly patients or in those with renal impairment or mild to moderate hepatic impairment. Conclusion: The pharmacological characteristics of pantoprazole-its ability to relieve GERD symptoms, long duration of action, equivalence of oral and TV formulations, and low potential for adverse drug interactions-make it a valuable option for the treatment of acid-related diseases.