Metabolic interactions of the proton-pump inhibitors lansoprazole, omeprazole and pantoprazole with other drugs.
OBJECTIVE
To analyse the metabolism of the proton-pump inhibitors lansoprazole, omeprazole and pantoprazole by cytochrome P450 (CYP) enzymes, and to assess the consequences for drug-drug interactions.


RESULTS
Lansoprazole, omeprazole and pantoprazole are extensively metabolized by several human cytochromes P450, most prominently by mephenytoin hydroxylase (CYP2C19) and nifedipine hydroxylase (CYP3A4). Only pantoprazole is also metabolized to a significant extent by a conjugating enzyme, a cytosolic sulfotransferase. The substrates and inhibitors of CYP2C19 and CYP3A4 and the known genetic polymorphism of CYP2C19 explain some but not all of the interactions of lansoprazole, and particularly the interactions of omeprazole with carbamazepine, diazepam, phenytoin and theophylline or caffeine. Both lansoprazole and omeprazole apparently also induce cytochromes P450 such as CYP1A2. This effect appears at lower doses of omeprazole in poor metabolizers of omeprazole. Of these three drugs, pantoprazole has by far the lowest potential for interactions, both in vitro (in microsomal studies) and in volunteer studies.


CONCLUSIONS
Proton-pump inhibitors interact with and are metabolized by several human cytochromes P450, but only pantoprazole is also metabolized by a sulfotransferase. This may partly explain why, in this group of proton-pump inhibitors, pantoprazole has the lowest potential for interactions with other drugs.
Meyer
U A
UA
Department of Pharmacology, Biozentrum of the University of Basel, Switzerland.
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases; D001562:Benzimidazoles / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D064747:Lansoprazole; D006899:Mixed Function Oxygenases / Q000235:genetics; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000077402:Pantoprazole; D010437:Peptic Ulcer / Q000188:drug therapy; D011110:Polymorphism, Genetic; D054328:Proton Pump Inhibitors; D013329:Structure-Activity Relationship; D013454:Sulfoxides / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D064747:Lansoprazole; D003577:Cytochrome P-450 Enzyme System; D000077402:Pantoprazole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole