Pharmacokinetic Drug Interaction Profiles of Proton Pump Inhibitors

Abstract

Proton pump inhibitors are used extensively for the treatment of gastric acid-related disorders because they produce a greater degree and longer duration of gastric acid suppression and, thus, better healing rates, than histamine H(2) receptor antagonists. The need for long-term treatment of these disorders raises the potential for clinically significant drug interactions in patients receiving proton pump inhibitors and other medications. Therefore, it is important to understand the mechanisms for drug interactions in this setting. Proton pump inhibitors can modify the intragastric release of other drugs from their dosage forms by elevating pH (e.g. reducing the antifungal activity of ketoconazole). Proton pump inhibitors also influence drug absorption and metabolism by interacting with adenosine triphosphate-dependent P-glycoprotein (e.g. inhibiting digoxin efflux) or with the cytochrome P450 (CYP) enzyme system (e.g. decreasing simvastatin metabolism), thereby affecting both intestinal first-pass metabolism and hepatic clearance. Although interactions based on the change of gastric pH are a group-specific effect and thus may occur with all proton pump inhibitors, individual proton pump inhibitors differ in their propensities to interact with other drugs and the extent to which their interaction profiles have been defined. The interaction profiles of omeprazole and pantoprazole have been studied most extensively. A number of studies have shown that omeprazole carries a considerable potential for drug interactions, since it has a high affinity for CYP2C19 and a somewhat lower affinity for CYP3A4. In contrast, pantoprazole appears to have lower potential for interactions with other medications. Although the interaction profiles of esomeprazole, lansoprazole and rabeprazole have been less extensively investigated, evidence suggests that lansoprazole and rabeprazole seem to have a weaker potential for interactions than omeprazole. Although only a few drug interactions involving proton pump inhibitors have been shown to be of clinical significance, the potential for drug interactions should be taken into account when choosing a therapy for gastric acid-related disorders, especially for elderly patients in whom polypharmacy is common, or in those receiving a concomitant medication with a narrow therapeutic index.

Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2

“…Proton pump inhibitors (PPIs) are highly effective in the treatment and symptomatic relief of peptic ulcers, by inhibiting H + ,K + -adenosine triphosphate (ATP)ase in the gastric parietal cells (16). The effects of pantoprazole (PPZ), one type of PPI, on PKM2 were hypothesized to be associated with the inhibitory efficacy of PPZ (17,18).…”

Successful treatment of a hemodialyzed patient with pure red cell aplasia associated with epoetin beta pegol therapy with cyclosporine

“…Thereafter, treatment with cyclosporine at a trough level of at least 150 ng/mL is necessary for maintaining remission [23]. In our case, the patient was taking omeprazole at the start of cyclosporine, and it is reported that omeprazole reduces the hepatic clearance of cyclosporine by inhibition of cytochrome P450 enzyme system, thus leading to higher cyclosporine levels with the same dosage [24]. Furthermore, the clearance rate of cyclosporine has shown to be diminished under uremic condition [25].…”

Clopidogrel and the possibility of drug–drug interaction in primary health care

“…The results of some clinical studies show that the best alternative for omeprazole, which is the moderate CYP2C19 inhibitor, is pantoprazole which seems to have much lower potential to inhibit CYP2C19. 12 In the current study, pantoprazole was recommended more often in comparison to other PPIs available, while some patients had not received omeprazole therapy yet.…”