Atorvastatin

Abstract

Atorvastatin is a synthetic HMG-CoA reductase inhibitor which lowers plasma cholesterol levels by inhibiting endogenous cholesterol synthesis. It also reduces triglyceride levels through an as yet unproven mechanism. Dose-dependent reductions in total cholesterol, low density lipoprotein (LDL)-cholesterol and triglyceride levels have been observed with atorvastatin in patients with hypercholesterolaemia and in patients with hypertriglyceridaemia. In large trials involving patients with hypercholesterolaemia, atorvastatin produced greater reductions in total cholesterol, LDL-cholesterol, apolipoprotein B and triglyceride levels than lovastatin, pravastatin and simvastatin. In patients with primary hypercholesterolaemia, the combination of atorvastatin and colestipol tended to produce larger reductions in LDL-cholesterol levels and smaller reductions in triglyceride levels than atorvastatin monotherapy. Although atorvastatin induced smaller reductions in triglyceride levels and more modest increases in high density lipoprotein (HDL)-cholesterol levels than either fenofibrate or nicotinic acid in patients with combined hyperlipidaemia, it produced larger reductions in total cholesterol and LDL-cholesterol. As with other HMG-CoA reductase inhibitors, the most frequently reported adverse events associated with atorvastatin are gastrointestinal effects. In comparative trials, atorvastatin had a similar adverse event profile to that of other HMG-CoA reductase inhibitors. Clinical data with atorvastatin are limited at present. However, with its ability to markedly reduce LDL-cholesterol levels, atorvastatin is likely to join other members of its class as a first-line agent for the treatment of patients with hypercholesterolaemia, if changes in lipid levels with atorvastatin convert to reductions in CHD mortality and morbidity. Atorvastatin may be particularly suitable for patients with heterozygous or homozygous familial hypercholesterolaemia because of the marked reductions in LDL-cholesterol experienced with the drug. Additionally, because of its triglyceride-lowering properties, atorvastatin appears to have the potential to become an appropriate treatment for patients with combined hyperlipidaemia or hypertriglyceridaemia.

Modelling of atorvastatin pharmacokinetics and the identification of the effect of a BCRP polymorphism in the Japanese population

“…Atorvastatin belongs to the class of HMG-CoA reductase inhibitors (statins) and is currently one of the most commonly used medications to treat lipid disorders and prevent cardiovascular events in high-risk individuals [1][2][3]. Similarly to other statins, atorvastatin has been associated with the development of skeletal muscle toxicity (myopathy).…”

“…Atorvastatin is administered in its active acid form, atorvastatin acid (ATA), and it is predominantly metabolised in the liver and gut wall by CYP3A4 [1,11]. It has a low (14%) oral bioavailability (F) due to the extensive first-pass metabolism and its renal elimination is negligible [11].…”

Synthesis of Indoles and Pyrroles Utilizing Iridium Carbenes Generated from Sulfoxonium Ylides

“…[19] The cyclization of β-enamino amide 10 with sulfoxonium ylide 11 in the presence of [Ir(COD)Cl]2 (2 mol%) and p-TSA (10 mol%) gave tetra substituted pyrrole [20] 12 in 58% yield. To gain insight into the reaction mechanisms, a series of control experiments were set up (Scheme 7).…”

From Flagrant to Fragrant: Reinventing Katherine Mansfield

“…50 As Lea acknowledges, 'Both in England and France, the rise of Lawrence's and Katherine's reputations undoubtedly contributed to the decline of Murry's'. 51 William Godwin also points out that 'Murry has not only been underestimated for his own contribution to literature, but has been adversely, even bitterly, criticised for not being the friend or the husband he should have been'. 52 Murry wrote extensively on his relationship with Lawrence, though at the time of Lawrence's death the pair had had little contact for many years.…”