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J Clin Pharmacol. 2015 May;55(5):534-42. doi: 10.1002/jcph.442. Epub 2015 Jan 14.

Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline.

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Furiex Pharmaceuticals Inc., Morrisville, NC, USA.


The effects of OATP1B1, OAT3, and MRP2 on the pharmacokinetics of eluxadoline, an oral, locally active, opioid receptor agonist/antagonist being developed for treatment of IBS-d were assessed in vivo. Coadministration of a single 200 mg dose of eluxadoline with cyclosporine, and probenecid increased eluxadoline systemic exposure [AUC(0-inf) ] by 4.4- and 1.4-fold, respectively, whereas peak exposure (Cmax ) increased 6.2-fold and 1.3-fold, respectively. Cyclosporine had little effect on renal clearance (CLren ) of eluxadoline whereas probenecid reduced CLren by nearly 50%. These study results suggested that sinusoidal OATP1B1-mediated hepatic uptake of eluxadoline (during first-pass and systemic extraction) plays a major role in its absorption and disposition, whereas OAT3-mediated basolateral uptake in the proximal renal tubules and MRP2-mediated canalicular and renal tubular apical efflux play only minor roles in its overall disposition. All treatments were safe and well tolerated.


cyclosporine; drug interaction; eluxadoline; pharmacokinetics; probenecid

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