In preliminary dose-titration studies, a marked decrease of plasma cholesterol is observed at 36 nmoles/kg/day KAT681 (T-0681), whereas doses higher than 36 nmoles/kg/day show no further lipid-lowering effect. In the subsequent study, New Zealand White (NZW) rabbits are fed a 0.2% cholesterol diet and dosed with 36 nmoles/kg/day KAT681 or a respective placebo control for 4 weeks. KAT681 treatment results in a 60% decrease of plasma cholesterol and a 70% decrease of plasma triglycerides[1]. In preliminary dose-titration studies in wild-type (WT) mice, a marked increase of hepatic SR-BI expression at 36 nmol/kg/d KAT681 (T-0681), and a concomitant 50% decrease of plasma cholesterol are observed. Higher doses than 36 nmol/kg/d show no further lipid-lowering effect. KAT681 significantly increases hepatic LDLrs in SR-BI KO mice (2-fold of controls, P<0.01), along with a marked decrease in plasma cholesterol[2].
