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Chemical Structure of Rosuvastatin Relative lipophilicity * -0.5 0.0 0.5 1.0 1.5 2.0 Rosuvastatin Cerivastatin Simvastatin Fluvastatin Atorvastatin Pravastatin.

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Presentation on theme: "Chemical Structure of Rosuvastatin Relative lipophilicity * -0.5 0.0 0.5 1.0 1.5 2.0 Rosuvastatin Cerivastatin Simvastatin Fluvastatin Atorvastatin Pravastatin."— Presentation transcript:

1 Chemical Structure of Rosuvastatin Relative lipophilicity * -0.5 0.0 0.5 1.0 1.5 2.0 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

2 Inhibition of HMG-CoA Reductase in Human Catalytic Domain 50 Three determinations, IC (nM) with 95% confidence limits Rosuva 5.4 100 10 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

3 Rosuvastatin: Single Dose Pharmacokinetics Rosuvastatin plasma concentration (ng/ml) 0.1 1 10 100 01020304050607080 Time post dose (hours) 5mg 10mg 20mg 40mg Presented at the ISA Meeting, Stockholm, June 2000

4 Systemic Availability Dose Faecal Elimination Urinary Excretion Renal Clearance Hepatic Extraction Tissues Absorption Biliary transport Systemic Availability (%) Cmax (ng/ml) Free drug (nM) Ceriva60100.2 Simva5445 Rosuva205312 Prava Atorva 18 12 50 ….. 56 …. Circulation

5 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) -70 -60 -50 -40 -30 -20 -10 0 atorvastatin atorvastatin rosuvastatin rosuvastatin placebo (P) placebo (P) P12.55102040801080 * * * * * * * 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; 88:504-508

6 0123456 -70 -60 -50 -40 -30 -20 -10 0 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

7 Baseline means across study: 1.2–1.5mmol/l (45–58mg/dl) -10 -5 0 5 10 15 20 Dose (mg) P12.55102040801080 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; 88:504-508

8 * ** * 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


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