Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy.
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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
Drug Transporter Kind Organism Pharmacological Action Actions Lansoprazole ATP-binding cassette sub-family G member 2 Protein Humans UnknownInhibitorDetails Methotrexate ATP-binding cassette sub-family G member 2 Protein Humans UnknownSubstrateDetails Omeprazole ATP-binding cassette sub-family G member 2 Protein Humans UnknownInhibitorDetails Pantoprazole ATP-binding cassette sub-family G member 2 Protein Humans UnknownSubstrateInhibitorDetails Rabeprazole ATP-binding cassette sub-family G member 2 Protein Humans UnknownInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareMethotrexatePantoprazole The excretion of Methotrexate can be decreased when combined with Pantoprazole. MethotrexateRabeprazole The excretion of Methotrexate can be decreased when combined with Rabeprazole. MethotrexateDexlansoprazole The excretion of Methotrexate can be decreased when combined with Dexlansoprazole. MethotrexateDexrabeprazole The excretion of Methotrexate can be decreased when combined with Dexrabeprazole. MethotrexateIlaprazole The excretion of Methotrexate can be decreased when combined with Ilaprazole.