A review of the pharmacologic and pharmacokinetic aspects of rosuvastatin.
Rosuvastatin is a new HMG-CoA reductase inhibitor with unique pharmacologic and pharmacokinetic properties. It has additional HMG-CoA reductase enzyme-binding interactions that cause tighter binding, has substantial active transport into hepatocytes, and has the lowest IC50 for sterol synthesis in hepatocytes. Rosuvastatin 10 mg and 80 mg dosages have superior low-density lipoprotein (LDL) cholesterol-lowering efficacy as compared to atorvastatin 10 mg and 80 mg. Rosuvastatin 10 mghas also been shown to have superior LDL reductions to 20 mg of both simvastatin and pravastatin. This agent can raise high-density lipoprotein (HDL) 8% to 12% and lower triglycerides by 10% to 35%. Rosuvastatin is a hydrophilic agent with poor penetration in extrahepatic tissue such as human umbilical vein endothelial cells and fibroblasts. It also has a low potential for cytochrome P450 drug interactions and can be dosed in the morning or night. In conclusion, rosuvastatin is an agent with molecular alterations that provide it with unique pharmacologic and phannacokinetic effects. As such, it is a novel and unique HMG-CoA reductase inhibitor for the treatment of hyperlipidemia.
White
C Michael
CM
University of Connecticut, School of Pharmacy, Drug Information Center, Storrs 06102-5037, USA.
D000818:Animals; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005464:Fluorobenzenes / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D027381:Liver-Specific Organic Anion Transporter 1 / Q000378:metabolism; D011743:Pyrimidines; D000068718:Rosuvastatin Calcium; D013329:Structure-Activity Relationship; D013449:Sulfonamides; D014018:Tissue Distribution; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D011743:Pyrimidines; D013449:Sulfonamides; D014280:Triglycerides; D000068718:Rosuvastatin Calcium