[Delayed elimination of methotrexate associated with use of DPP-4 inhibitors during high-dose methotrexate therapy]

This study investigated the increase in blood concentration of methotrexate (MTX) due to delayed elimination when a dipeptidyl peptidase-4 (DPP-4) inhibitors with organic anion transporter 3 (OAT3) inhibitory effects was co-administered with high-dose methotrexate therapy (HD-MTX). During the study period, five patients received a DPP-4 inhibitors. Delayed MTX elimination was confirmed in two of these patients 48 hours after the start of MTX administration. Both patients had received a DPP-4 inhibitors with OAT3 inhibitory effects. Previous literature has reported that MTX elimination may be delayed by the co-administration of drugs that have OAT3 inhibitory effects, but no reports have addressed the impact on actual blood concentration. This study suggests that co-administration of a DPP-4 inhibitors with OAT3 inhibitory effects during HD-MTX may contribute to an increase in blood MTX concentration 48 hours after the start of MTX administration. When conducting HD-MTX therapy, consideration should be given to switching to an alternative treatment.