Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy.

Article Details

Citation

Suzuki K, Doki K, Homma M, Tamaki H, Hori S, Ohtani H, Sawada Y, Kohda Y

Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy.

Br J Clin Pharmacol. 2009 Jan;67(1):44-9. doi: 10.1111/j.1365-2125.2008.03303.x. Epub 2008 Nov 17.

PubMed ID
19076159 [ View in PubMed
]
Abstract

AIM: To assess whether or not co-administration of proton pump inhibitors (PPIs) is a risk factor for delayed elimination of plasma methotrexate (MTX) in high-dose MTX (HDMTX) therapy for malignant diseases. METHODS: To assess the effects of PPI co-administration on elimination of plasma MTX, we examined plasma MTX concentration data on 171 cycles of HDMTX therapy performed in 74 patients. We performed multiple logistic regression analysis to evaluate PPI co-administration as a risk factor. Inhibitory potencies of omeprazole, lansoprazole, rabeprazole and pantoprazole on MTX transport via breast cancer resistance protein (BCRP, ABCG2) were also investigated in an in vitro study using membrane vesicles expressing human BCRP. RESULTS: We identified co-administration of PPIs as a risk factor for delayed elimination (odds ratio 2.65, 95% confidence interval 1.03, 6.82) as well as renal and liver dysfunction. All four PPIs inhibited BCRP-mediated transport of MTX, with half-maximal inhibitory concentrations of 5.5-17.6 microM--considerably higher than the unbound plasma concentrations of the PPIs. CONCLUSIONS: Our results support previous findings suggesting that PPI co-administration is associated with delayed elimination of plasma MTX in patients with HDMTX therapy. This drug interaction, however, cannot be explained solely by the inhibitory effects of PPIs on BCRP-mediated MTX transport.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
LansoprazoleATP-binding cassette sub-family G member 2ProteinHumans
Unknown
Inhibitor
Details
MethotrexateATP-binding cassette sub-family G member 2ProteinHumans
Unknown
Substrate
Details
OmeprazoleATP-binding cassette sub-family G member 2ProteinHumans
Unknown
Inhibitor
Details
PantoprazoleATP-binding cassette sub-family G member 2ProteinHumans
Unknown
Substrate
Inhibitor
Details
RabeprazoleATP-binding cassette sub-family G member 2ProteinHumans
Unknown
Inhibitor
Details
Drug Interactions
DrugsInteraction
Methotrexate
Pantoprazole
The excretion of Methotrexate can be decreased when combined with Pantoprazole.
Methotrexate
Rabeprazole
The excretion of Methotrexate can be decreased when combined with Rabeprazole.
Methotrexate
Dexlansoprazole
The excretion of Methotrexate can be decreased when combined with Dexlansoprazole.
Methotrexate
Dexrabeprazole
The excretion of Methotrexate can be decreased when combined with Dexrabeprazole.
Methotrexate
Vonoprazan
The excretion of Methotrexate can be decreased when combined with Vonoprazan.
Interactions
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