Pharmacokinetic Drug Interaction Profiles of Proton Pump Inhibitors: An Update

Abstract

Proton pump inhibitors (PPIs) are used extensively for the treatment of gastric acid-related disorders, often over the long term, which raises the potential for clinically significant drug interactions in patients receiving concomitant medications. These drug–drug interactions have been previously reviewed. However, the current knowledge is likely to have advanced, so a thorough review of the literature published since 2006 was conducted. This identified new studies of drug interactions that are modulated by gastric pH. These studies showed the effect of a PPI-induced increase in intragastric pH on mycophenolate mofetil pharmacokinetics, which were characterised by a decrease in the maximum exposure and availability of mycophenolic acid, at least at early time points. Post-2006 data were also available outlining the altered pharmacokinetics of protease inhibitors with concomitant PPI exposure. New data for the more recently marketed dexlansoprazole suggest it has no impact on the pharmacokinetics of diazepam, phenytoin, theophylline and warfarin. The CYP2C19-mediated interaction that seems to exist between clopidogrel and omeprazole or esomeprazole has been shown to be clinically important in research published since the 2006 review; this effect is not seen as a class effect of PPIs. Finally, data suggest that coadministration of PPIs with methotrexate may affect methotrexate pharmacokinetics, although the mechanism of interaction is not well understood. As was shown in the previous review, individual PPIs 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 sodium (pantoprazole-Na) have been studied most extensively. Several studies have shown that omeprazole carries a considerable potential for drug interactions because of its high affinity for CYP2C19 and moderate affinity for CYP3A4. In contrast, pantoprazole-Na appears to have lower potential for interactions with other medications. Lansoprazole and rabeprazole also seem to have a weaker potential for interactions than omeprazole, although their interaction profiles, along with those of esomeprazole and dexlansoprazole, have been less extensively investigated. Only a few drug interactions involving PPIs are of clinical significance. Nonetheless, the potential for drug interactions should be considered when choosing a PPI to manage gastric acid-related disorders. This is particularly relevant for elderly patients taking multiple medications, or for those receiving a concomitant medication with a narrow therapeutic index.

The Use of Betaine HCl to Enhance Dasatinib Absorption in Healthy Volunteers with Rabeprazole-Induced Hypochlorhydria

“…Drug-drug interactions due to ARAs, particularly the PPIs, can involve significant reductions in drug absorption due to elevations in pH in the stomach and upper gastrointestinal regions (17), or increased drug exposure due to inhibition of the cytochrome P450 (CYP) metabolizing enzymes (18). Most PPIs are primarily metabolized in the liver by the CYP2C19 and CYP3A4 isoforms (19), and have the potential to cause drug-drug interactions with other drugs metabolized by the same CYPs.…”

Interaction between Warfarin and Apple Juice

“…16 Pantoprazole has low potential to interact with other medications, and there are no clinically significant metabolic interactions when pantoprazole is combined with warfarin. 5,17 However, the pantoprazole product monograph states that a few isolated cases of changes in INR have been reported during concomitant treatment with warfarin in the postmarketing period. 18 The patient had been receiving pantoprazole concurrently with warfarin for 3 years before the current admission.…”

Effectiveness of Rabeprazole for the Treatment of Acid-Related Diseases

“…В контексте этого положения боль-шое значение имеет метаболизм в организме различных ИПП. Современные работы показали, что рабепразол метаболизируется энзиматическим путем, практически не вступает в лекарственное взаимодействие, тогда как оме-празол метаболизируется преимущественно в системе CYP2С19, в связи с чем его влияние на метаболизм клопи-догрела является весьма значительным [19]. В клиниче-ском исследовании у 218 пациентов рабепразол в дозе 20 мг/сут показал высокую эффективность для профилактики гастродуоденальных осложнений у пациентов, получав-ших аспирин или клопидогрел [20].…”