The coadministration of methotrexate (MTX) and proton pump inhibitors (PPIs) can result in a pharmacokinetic interaction that delays MTX elimination and subsequently increases the MTX blood concentrations. Human organic anion transporters (hOATs) are responsible for the renal tubular secretion of MTX and are thought to be involved in this drug interaction. The aim of this study was to evaluate the inhibitory potencies of PPIs on hOAT1 and hOAT3, which are the two isoforms of OATs predominantly expressed in kidney proximal tubules. Using stably transfected cell systems that express the uptake transporters human embryonic kidney (HEK)-hOAT1 and HEK-hOAT3, we analyzed the inhibitory potencies of omeprazole, lansoprazole, and pantoprazole on OAT-mediated [
Clinical Therapeutics e74Volume 35 Number 8Saccounting for 21.2% and 16.2% of total AED consumption (DDD 163.7 and 125.2, respectively). In the same year, oxcarbazepine and lamotrigine were the most used new AEDs (10.91% and 10.79% of total; DDD 84.1 and 83.2, respectively), while gabapentin and pregabalin exhibited the higher incidence of use. The main indication of use was epileptic disorders for older AEDs and neuropathic pain for newer AEDs. A high number of patients treated with older AEDs, in particular carbamazepine, phenobarbital, and valproic acid, received coprescription at clinically relevant interaction risk. Among newer AEDs, lamotrigine showed a high annual rate of possible interaction. Conclusion: Significant differences were shown in the prescribing pattern of newer and older medications: older AEDs were mainly used in the treatment of epileptic disorders, while newer compounds were also preferred for conditions other than epilepsy, in particular neuropathic pain. The fall in the use of newer AEDs during 2007 agreed with revised reimbursement criteria for gabapentin and pregabalin. The coprescription should be evaluated with caution and avoided if possible. Drugs at risk of interactions should be replaced with others having same indication of use.
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