Discovery and development of statins as they directly compete with the endogenous substrate for the active site cavity of HMGR. Statins are also noncompetitive with the cosubstrate NADPH (nicotinamide adenine dinucleotide phosphate). By blocking the HMGR enzyme they inhibit the synthesis of cholesterol via the mevalonate pathway. The end result is lower LDL (Low Density Lipoprotein), TG (Triglycerides) and total cholesterol levels as well as increased HDL (High Density Lipoprotein) levels in serum). The ideal statin should have the following properties: One of the main design objectives of statin design is the selective inhibition of HMGR in the liver, as cholesterol synthesis in non-hepatic cells
Discovery and development of statins dominant. CYP3A4 isoenzyme is the most predominant isoform involved in metabolism of lovastatin, simvastatin, atorvastatin and cerivastatin. CYP2C9 isoenzyme is the most predominant isoform involved in metabolism of Fluvastatin, but CYP3A4 and CYP2C8 isoenzymes also contribute to the metabolism of Fluvastatin. Rosuvastatin is metabolized to a small degree by CYP2C9 and to a lesser extent by CYP2C19 isoenzymes. Pravastatin is not metabolized by CYP isoenzymes to any appreciable extent. The statins that have the ability to be metabolized by multiple CYP isoenzymes may therefore avoid drug accumulation when one of the pathways is inhibited by co-administered drugs. With the recent