Discovery and development of statins trials showed very good inhibitory effect as in clinical trials, however in a long term toxicity study in dogs it resulted in toxic effects at higher doses and as a result was believed to be too toxic to be given to humans. In 1978, Alfred Alberts and colleagues at Merck Research Laboratories discovered a new natural product in a fermentation broth of "Aspergillus terreus", their product showed good HMGR inhibition and they named the product mevinolin, which later became known as lovastatin. The cholesterol controversy began in the early promotion of statins. Statins are a competitive antagonists of HMG CoA,
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