Pharmacokinetics, metabolism and interactions of acid pump inhibitors - Focus on omeprazole, lansoprazole and pantoprazole

This review updates and evaluates the currently available information regarding the pharmacokinetics, metabolism and interactions of the acid pump inhibitors omeprazole, lansoprazole and pantoprazole. Differences and similarities between the compounds are discussed. Omeprazole, lansoprazole and pantoprazole are all mainly metabolised by the polymorphically expressed cytochrome P450 (CYP) isoform S-mephenytoin hydroxylase (CYP2C19), which means that within a population a few individuals (3% of Caucasians) metabolise the compounds slowly compared with the majority of the population. For all 3 compounds, the area under the plasma concentration-versus-time curve (AUG) for a slow metaboliser is, in general, approximately 5 times higher than that in an average patient, Since all 3 compounds are considered safe and well tolerated, and no dosage-related adverse drug reactions have been identified, this finding seems to be of no clinical relevance. The acid pump inhibitors seem to be similarly handled in the elderly, where a somewhat slower elimination can be demonstrated compared with young individuals. In patients with renal insufficiency, omeprazole is eliminated as in healthy individuals, whereas the data on lansoprazole and pantoprazole are unresolved. In patients with hepatic insufficiency, as expected, the elimination rates of all 3 compounds are substantially decreased. No clinically relevant effects on specific endogenous glandular functions, such as the adrenal (cortisol), the gonads or the thyroid, were demonstrated for omeprazole and pantoprazole, whereas a few minor concerns have been raised regarding lansoprazole. The absorption of some compounds, e.g. digoxin, might be altered as a result of the increased gastric pH obtained during treatment with acid pump inhibitors, and, accordingly, similar effects are expected irrespective of which acid pump inhibitor is given. The effect of the acid pump inhibitors on enzymes in the liver has been intensely debated, and some authors have claimed that lansoprazole and pantoprazole have less potential than omeprazole to interact with other drugs metabolised by CYP. However, after assessment of available data in this area, the conclusion is Chat all 3 acid pump inhibitors have a very limited potential for drug interactions at the CYP level. In addition, the small effects on CYP reported for these compounds are rarely of any clinical relevance, considering the normal intra- (and inter-)individual variations in metabolism observed for most drugs. In conclusion, omeprazole, lansoprazole and pantoprazole are structurally very similar, and an evaluation of available data indicates that also with respect to pharmacokinetics, metabolism and interactions in general they demonstrate very similar properties, even though omeprazole has been mon thoroughly studied with regard to different effects.