Chemical Structure of Rosuvastatin Relative lipophilicity * Rosuvastatin Cerivastatin Simvastatin Fluvastatin Atorvastatin Pravastatin * log D at pH 7.4 Statin Pharmacophore OO N N S N OH OH O O CH 3 CH 3 CH 3 F CH 3 Ca (3R, 5S) Presented at XXII Congress of European Society of Cardiology, August 26-30, 2000, Amsterdam, The Netherlands

Inhibition of HMG-CoA Reductase in Human Catalytic Domain 50 Three determinations, IC (nM) with 95% confidence limits Rosuva Ceriva* 10.0 Atorva 8.2 Fluva** 27.6 Simva* 11.2 Prava ** 44.1 Significance of difference from rosuva, * p<0.05, ** p<0.001 IC 50 (nM) (log scale) Presented at XXII Congress of European Society of Cardiology, August 26-30, 2000, Amsterdam, The Netherlands Rosuvastatin and HMG-CoA reductase activity

Rosuvastatin: Single Dose Pharmacokinetics Rosuvastatin plasma concentration (ng/ml) Time post dose (hours) 5mg 10mg 20mg 40mg Presented at the ISA Meeting, Stockholm, June 2000

Systemic Availability Dose Faecal Elimination Urinary Excretion Renal Clearance Hepatic Extraction Tissues Absorption Biliary transport Systemic Availability (%) Cmax (ng/ml) Free drug (nM) Ceriva Simva5445 Rosuva Prava Atorva ….. 56 …. Circulation

NB: No statistical comparisons were made with open-label atorvastatin Baseline means across study: 4.7– 5.1mmol/l (180–197mg/dl) * p<0.001 (rosuvastatin vs. placebo) Dose (mg) atorvastatin atorvastatin rosuvastatin rosuvastatin placebo (P) placebo (P) P * * * * * * * Percentage change ( from baseline in LDL-C Percentage change (±SE) from baseline in LDL-C Dose-related reductions of LDL-C with Rosuvastatin Olsson AG, Am J Cardiol, 2001; 88:

Week placebo rosuvastatin 10mg rosuvastatin 80mg Mean percentage change in LDL-C Rosuvastatin time dependancy of LDL-C Reduction Presented at XXII Congress of European Society of Cardiology, August 26-30, 2000, Amsterdam, The Netherlands

Baseline means across study: 1.2–1.5mmol/l (45–58mg/dl) Dose (mg) P atorvastatin atorvastatin rosuvastatin rosuvastatin placebo placebo * * Percentage change ( from baseline in HDL-C Percentage change (±SE) from baseline in HDL-C NB: No statistical comparisons were made with open-label atorvastatin * p<0.05 (rosuvastatin vs. placebo) Rosuvastatin and HDL-C Rosuvastatin and HDL-C Olsson AG, Am J Cardiol, 2001; 88:

* ** * p>0.01 vs placebo ** p>0.001 vs placebo Presented at XIV International Symposium on Drugs Affecting Lipid Metabolism, September 9-12, 2001, New York, NY, USA Rosuvastatin and plasma TG at 6 weeks in hypertriglyceridemic patients