Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein.

Article Details

Citation

Pauli-Magnus C, Rekersbrink S, Klotz U, Fromm MF

Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein.

Naunyn Schmiedebergs Arch Pharmacol. 2001 Dec;364(6):551-7.

PubMed ID
11770010 [ View in PubMed
]
Abstract

Proton pump inhibitors are a class of drugs which are widely prescribed for acid-related diseases. They are primarily metabolized by CYP2C19 and CYP3A4. It is unknown so far whether proton pump inhibitors are also substrates of the ATP-dependent efflux transporter P-glycoprotein. Moreover, it is not established whether proton pump inhibitors are also inhibitors of P-glycoprotein function. The aim of our study was therefore to characterize omeprazole, lansoprazole and pantoprazole as P-glycoprotein substrates and inhibitors. Polarized transport of these compounds was assessed in P-glycoprotein-expressing Caco-2 and L-MDR1 cells. Inhibition of P-glycoprotein-mediated transport was determined using the cyclosporine analogue PSC-833 (valspodar) as P-glycoprotein inhibitor. Inhibition of efflux transport by omeprazole, lansoprazole and pantoprazole was assessed using digoxin as P-glycoprotein substrate. At concentrations of 5 microM, basal-to-apical transport of omeprazole, lansoprazole and pantoprazole was greater than apical-to-basal transport in Caco-2 and L-MDRI cells. Addition of PSC-833 (1 microM) showed a clear effect only for lansoprazole, suggesting that other transporters contribute to omeprazole and pantoprazole cellular translocation. Furthermore, all of the tested compounds inhibited digoxin transport with IC50 values of 17.7, 17.9 and 62.8 microM for omeprazole, pantoprazole and lansoprazole, respectively. In summary, our data provide evidence that proton pump inhibitors are substrates and inhibitors of P-glycoprotein. These findings might explain some of the drug interactions with proton pump inhibitors observed in vivo.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
EsomeprazoleATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Details
LansoprazoleATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Details
OmeprazoleATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Details
PantoprazoleATP-dependent translocase ABCB1ProteinHumans
Unknown
Substrate
Inhibitor
Details
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
OmeprazoleATP-dependent translocase ABCB1IC 50 (nM)17700N/AN/ADetails
PantoprazoleATP-dependent translocase ABCB1IC 50 (nM)17900N/AN/ADetails