METABOLIC INTERACTIONS OF THE PROTON-PUMP INHIBITORS LANSOPRAZOLE, OMEPRAZOLE AND PANTOPRAZOLE WITH OTHER DRUGS

Purpose: To analyse the metabolism of the proton-pump inhibitors lanso prazole, omeprazole and pantoprazole by cytochrome P450 (CYP) enzymes, and to assess the consequences for drug-drug interactions. Results of data analysis: Lansoprazole, omeprazole and pantoprazole are extensiv ely 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 c onjugating enzyme, a cytosolic sulfotransferase. The substrates and in hibitors of CYP2C19 and CYP3A4 and the known genetic polymorphism of C YP2C19 explain some but not all of the interactions of lansoprazole, a nd particularly the interactions of omeprazole with carbamazepine, dia zepam, phenytoin and theophylline or caffeine. Both lansoprazole and o meprazole apparently also induce cytochromes P450 such as CYP1A2. This effect appears at lower doses of omeprazole in poor metabolizers of o meprazole. Of these three drugs, pantoprazole has by far the lowest po tential for interactions, both in vitro (in microsomal studies) and in volunteer studies. Conclusions: Proton-pump inhibitors interact with and are metabolized by several hu man cytochromes P450, but on ly pant oprazole is also metabolized by a sulfotransferase. This may partly ex plain why, in this group of proton-pump inhibitors, pantoprazole has t he lowest potential for interactions with other drugs.