Drug Overview
Pfizer’s Lipitor (atorvastatin calcium) acts by competitively inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG Co-A) reductase. HMG Co-A reductase is a rate-limiting enzyme that converts HMG Co-A to mevalonate in the mevalonate pathway. This hepatic pathway is responsible for synthesizing various molecules, including cholesterol. The binding of Lipitor at the active site not only prevents substrate binding but also alters the enzyme’s conformation, preventing the attainment of a functional structure. The reduction in de novo cholesterol synthesis results in upregulation of low-density lipoprotein (LDL) receptors on hepatocytes, consequently increasing LDL endocytosis. Lipitor is also effective at treating homozygous familial hypercholesterolemia, despite the fact that LDL receptors are non-functional in patients with this disease. This is explained by Lipitor’s ability to limit cholesterol availability for the hepatic synthesis of lipoproteins containing apolipoprotein B, such as LDL.
Sales of Lipitor have declined as a result of competition from generic versions of the drug. Lipitor will experience further competition from generic versions of its major competitor, Crestor (rosuvastatin calcium; AstraZeneca/AbbVie/Shionogi), which entered the US market in May 2016. Pfizer has also recently given up on its efforts to switch Lipitor to an over-the-counter treatment, which will prevent the drug from recovering any revenues in the dyslipidemia market.
Pfizer’s Lipitor (atorvastatin calcium) acts by competitively inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG Co-A) reductase. HMG Co-A reductase is a rate-limiting enzyme that converts HMG Co-A to mevalonate in the mevalonate pathway. This hepatic pathway is responsible for synthesizing various molecules, including cholesterol. The binding of Lipitor at the active site not only prevents substrate binding but also alters the enzyme’s conformation, preventing the attainment of a functional structure. The reduction in de novo cholesterol synthesis results in upregulation of low-density lipoprotein (LDL) receptors on hepatocytes, consequently increasing LDL endocytosis. Lipitor is also effective at treating homozygous familial hypercholesterolemia, despite the fact that LDL receptors are non-functional in patients with this disease. This is explained by Lipitor’s ability to limit cholesterol availability for the hepatic synthesis of lipoproteins containing apolipoprotein B, such as LDL.
Sales of Lipitor have declined as a result of competition from generic versions of the drug. Lipitor will experience further competition from generic versions of its major competitor, Crestor (rosuvastatin calcium; AstraZeneca/AbbVie/Shionogi), which entered the US market in May 2016. Pfizer has also recently given up on its efforts to switch Lipitor to an over-the-counter treatment, which will prevent the drug from recovering any revenues in the dyslipidemia market.
Table of Contents
OVERVIEW
LIST OF FIGURES
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