الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 202 |  |  |
| | | from | 202 | | |
Abstract
Atorvastatin, a member of the class of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-C0A) reductase inhibitors, is one of the most potent drugs for the management of a wide variety of dyslipidemias. Atorvastatin undergoes extensive metabolism primarily by cytochrome P450 3A (CYP3A) in the liver to form two active metabolites, ortho-hydroxy atorvastatin and para-hydroxy atorvastatin, and various 13-oxidation products. About 70% of the HMG-CoA reductase inhibitory activity associated with atorvastatin has been attributed to its active metabolites, the ortho- and para-hydroxylated derivatives, which are equipotent to the parent drug. Reductions in plasma levels of total cholesterol, low density lipoprotein (LDL)-cholesterol, very low density lipoprotein (VLDL)-cholesterol, triglycerides and apolipoprotein B (apo B) have been demonstrated with the use of atorvastatin in a number of clinical studies.
Giventhat atorvastatin is among the most widely prescribed lipid-lowering drugs and that it has long elimination half-life and can achieve relatively high systemic concentrations in humans after multiple doses, concerns have been raised about its potential to elicit adverse effects outside its cholesterol-lowering role. One of the major disadvantages that may occur in association with atorvastatin therapy is elevation of serum transaminase levels. In these cases, discontinuation of atorvastatin therapy leads to
normalization in hepatic enzymes. Therefore, in patients with persistent elevations in transaminase levels greater than 3 times the upper limit of the normal range, reduction of dosage or cessation of aton’astatin therapy is recommended. Whether transaminase elevation with atorvastatin therapy constitutes true hepatotoxicity has not been clearly determined.