Pharmacologic basis of pantoprazole dosing

Abstract

Abstract 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 intravenous (IV) formulations. Like other PPIs, pantoprazole is efficacious in the treatment of GERD and other acid-related diseases. It has high specificity for the relevant binding sites on activated proton pumps, and its profile of pH activation suggests that its activated cationic sulfenamide derivative should reach much higher concentrations at the site of acid production on the parietal cell than elsewhere in the body. These features suggest that pantoprazole will act specifically on parietal cells, with little propensity to cause unwanted systemic effects. Pantoprazole has minimal interaction with the cytochrome P-450 enzymes and no known drug interactions, suggesting that 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 pharmacokinetics; studies indicate a linear dose response increasing up to 40 mg once daily, with some additional benefit at higher dosages for patients with chronic hypersecretory conditions. The recommended dosage of pantoprazole in GERD is 40 mg once daily. This dosage suppresses intragastric pH throughout the day and some of the night, providing relief of nighttime gastroesophageal reflux. Both the oral and IV formulations of pantoprazole can be dosed at 40 mg once daily for patients with GERD, and apparent dose equivalence 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 or disease healing. Dosage adjustments are rarely needed for special situations such as severe ulcer disease. No dosage adjustment is necessary in elderly 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 IV formulations, and low potential for adverse drug interactions—make it a valuable option for the treatment of acid-related diseases.