Statins elimination

The most important class of cholesterol-lowering agents is the statins. These include lovastatin (Mevacor), simvastatin (Zocor), pravastatin (Pravachol), and atorvastatin (Lipitor), among others. These molecules work, in modest part, by inhibiting biosynthesis of cholesterol and, in larger part, by increasing the rate at which cholesterol is eliminated by the body. Let s have a look at this in more detail. 

Statins are the most important class of cholesterol-lowering drugs. They are inhibitors of an enzyme on the route to synthesis of cholesterol. As a result, there is an increase of LDL receptors in the liver, the only important mechanism for elimination of cholesterol from the body. 

The hydrophilic statins (pravastatin, rosuvastatin) are only partly metabolised by the liver [1, 17, 19]. Pravastatin is also metabolised in the stomach [26]. The pharmacokinetics of pravastatin have been shown to change in liver disease, despite its dual route (renal and hepatic) of elimination [27]. Nonetheless, it has been used in liver disease and has been suggested as the statin of choice [26]. Liver metabolism is of minor importance in the clearance of rosuvastatin and its pharmacokinetics are not altered by mild to moderate liver impairment. However, the area under the curve (AUC) is increased in severe liver impairment [1]. Clinical experience with rosuvastatin in liver disease is lacking, and it therefore cannot be recommended. 

Myalgias related to statin use are quite common, occurring in up to 10 % of patients exposed [19]. Clinicians often measure circulating levels of nonspecific markers of myocyte damage (e.g., CK) to estimate severity. Myalgias accompanied by a mild elevation in serum CK level occur in approximately 1 % of patients exposed [20, 21], Myopathy (CK >10-fold upper limit of normal) is less common, 0.1 %, and rhabdomyolysis (CK >50-fold upper limit of normal) is extremely rare [14, 15]. Graham and colleagues surveyed more than 250,000 statin-exposed patients, and reported rhabdomyolysis rates of 0.000044 events per person-year [18]. Similar rates have been observed for more than 100,000 first-time statin users followed in the UK over a course of 20 months [22], Event rates increase when statins are used in the presence of other medications known to alter their absorption, distribution, metabolism, and elimination (ADME) [23, 24], Event rates also increase with comorbidity (e.g., thyroid disease) [21, 25]. 

The clinical severity of statin-induced muscle toxicity is clearly influenced by variability in enzymes modulating statin disposition (absorption, distribution, metabolism, and elimination, ADME) (Fig. 1) [40], While many statins undergo phase I oxidation (atorvastatin, fluvastatin, lovastatin, simvastatin), the impact of phase I oxidation on others (pitavastatin, pravastatin, rosuvastatin) is very limited [41],... 

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