In vivo study | Torcetrapib (< 100 mg per day) changed the plasma distribution of CETP after 2 hours in the young healthy group because the apparent molecular weight of CETP migrated to a larger form. In the young healthy group, 10 mg, 30 mg, 60 mg and 120 mg daily and 120 mg Torcetrapib twice daily increased plasma levels by HDL-C, respectively, by 16%, 28, 62, 73% and 91% while TPC did not change significantly. In patients at high risk of cardiovascular disease, Torcetrapib treatment for 12 hours resulted in a 72.1% increase in HDL cholesterol and a 24.9% decrease in LDL cholesterol, a 5.4mm increase in systolic blood pressure and a decrease in serum potassium concentration, serum sodium concentration, bicarbonate concentration and aldosterone concentration increased. Torcetrapib 60mg per day and 50% mg per day increased HDL cholesterol levels by 60% and in the healthy and moderately hyperlipidaemic groups, respectively. Torcetrapib 60mg per day increased HDL-mediated net cholesterol efflux from foam cells, mainly due to increased HDL concentration, while 120mg per day increased net cholesterol efflux, I .e., due to increased HDL concentration, also due to the increased efflux at the matched HDL concentration. In rabbits fed the Atherogenic diet, Torcetrapib (90 mg/kg/day) inhibited CE metastasis by 70% and increased plasma levels by an average of HDL-C by a factor of 3, increased the level apoA-I by a factor of 2.5. Torcetrapib treatment in rabbits fed the Atherogenic diet resulted in a multiple increase in HDL-C AUC levels with a decrease in aortic lesion area, in addition to a 60% decrease in aortic free cholesterol (FC) and cholesterol ester (EC). Torcetrapib treated rabbits significantly stimulated free cholesterol efflux compared to serum. |