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We evaluated the effects of probenecid, a potent organic anion transporter 1 (OAT1) and OAT3 inhibitor, on the pharmacokinetics and safety of ritobegron, a selective β3-adrenoceptor agonist, in healthy men. Twelve healthy men were administered a single oral dose of ritobegron (20 mg) alone or in combination with probenecid 2 hours before administration of ritobegron. In the combination sequence, additional doses of probenecid were administered 4 and 10 hours after the administration of ritobegron. Probenecid increased the Cmax of KUC-7322, an active form of ritobegron, and the AUC0-48 h by 1.39 and 2.93 times, respectively. Probenecid prolonged the t1/2 of KUC-7322 from 1.6 to 3.4 hours and decreased the renal clearance and cumulative fraction of KUC-7322 excreted in urine from 18.5 to 4.9 L/h and from 64.7% to 49.7%, respectively. Coadministration of probenecid did not influence adverse events, blood pressure, pulse rate, or heart rate relative to ritobegron alone. Although probenecid inhibited renal tubule secretion of KUC-7322 via OAT3 and increased KUC-7322 exposure, it did not influence adverse effects or vital signs. Therefore, clinically significant drug-drug interactions are unlikely to occur when probenecid is administered in combination with OAT3 inhibitors or substrates. [ABSTRACT FROM AUTHOR]