The pharmacokinetic profile of ritobegron, a novel, selective β3-adrenoceptor agonist, was investigated in rats. Ritobegron, an ethyl ester prodrug of the active compound KUC-7322, or KUC-7322 itself was orally administered (10 mg/kg). Ethyl esterification resulted in a 10-fold increase in the area under the plasma concentration-time curve (AUC(0-t)), as compared to KUC-7322. Following intravenous administration of KUC-7322 (1 mg/kg), total blood clearance was 1.36 L/h/kg, suggesting that intrinsic hepatic clearance is the rate-limiting step in KUC-7322 excretion. When ritobegron was orally administered (0.3, 1, 3, and 10 mg/kg), plasma concentrations of KUC-7322 rapidly increased and reached a maximum concentration (C(max)) at 0.25 to 0.31 h. KUC-7322 levels rapidly decreased, with a half-life (t 1/2) of 0.42 to 1.37 h thereafter. AUC(0-t) did not show a dose-dependent increase. The bioavailability of KUC-7322 was estimated to be 4%. Following oral administration of [14C]ritobegron (3 mg/kg), radioactivity concentrations in tissues rapidly increased and declined in parallel with changes in plasma concentration. In most of tissues, excluding the liver, kidney, urinary bladder, stomach and small intestine, radioactivity concentrations were lower than that in plasma. In plasma, bile, urine, and feces, KUC-7322 and its glucuronide, sulfate, and glutathione conjugates were detected. The glucuronide conjugate of KUC-7322 was the predominant metabolite in bile, plasma, and urine, and KUC-7322 was predominant in feces. Ritobegron was not detected in any of the samples. The cumulative excretion of radioactivity in urine and feces were 28.7% and 68.3% of the dose, respectively, up to 120 h after administration.