Turofexorate isopropyl (WAY-362450) also shows potent effects on cholesterol and triglyceride lowering in LDLR^-/- mice and antiatherogenic activity with respect to reduction of aortic arch lesions. Oral administration of Turofexorate isopropyl (WAY-362450) to LDLR^-/- mice results in lowering of cholesterol and triglycerides. Chronic administration in an atherosclerosis model results in significant reduction in aortic arch lesions. Turofexorate isopropyl (WAY-362450) is dosed in rat at 3 mg/kg (po and iv) and shows good oral bioavailability (38%). There is a protracted half-life of 25 h, modest volume of distribution, and low clearance (3.3 L/kg, ~10% of hepatic blood flow). Additional pharmacokinetic studies in mice and higher species have been completed, and the data will be reported elsewhere^[1]. In rats, Turofexorate isopropyl (WAY-362450) results in an elevation in HDLc levels, whereas in hamsters it causes a reduction similar to that observed in mice^[2] Treatment of wild-type mice with 30 mg/kg Turofexorate isopropyl (WAY-362450) results in induction of SHP expression in wild-type mice but not in FXR^-/- mice. Consistent with the known effects of SHP induction on bile acid synthetic gene expression, Turofexorate isopropyl (WAY-362450) strongly represses expression of the CYP8B1 bile acid synthetic gene in wild-type mice but had no effect on CYP8B1 gene expression in FXR^-/- mice^[3].