Drugs atorvastatin

The cholesterol-lowering drug atorvastatin, marketed as Lipitor, is an example where biocatalysis research has been applied extensively and is in industrial use. The enzyme 2-deoxyribose-5-phosphate aldolase (DERA) has been a target of directed evolution for the production of atorvastatin intermediates [8,9,71]. DeSantis and coworkers [8,9] used structure-based... 

The absorption of highly lipophilic drugs (atorvastatin, simvastatin, ezetimibe, fibrates) may be reduced in cholestasis if they require bile salts for their absorption. 

PROTON PUMP INHIBITORS LIPID-LOWERING DRUGS-ATORVASTATIN Possible t efficacy and adverse effects of atorvastatin Inhibition of P-gp 1 first pass clearance Monitor closely... 

Many valuable compounds arc arotnatic in part, including steroids such as estrone and well-known pharmaceuticals such as the cholesterol-lowering drug atorvastatin, marketed as Lipitor. Benzene itself has been found to cause bone marrow depression and a consequent lowered white blood cell count on prolonged exposure. Benzene should therefore be handled cautiously if iLsed as a laboratorv solvent. 

Cholesterol and cholesterol-lowering drugs atorvastatin (Lipitor) and simvastatin (Zocor) (Section 29.8B)... 

Slc21al) estrone-S, ochratoxin A, thyroid hormones, bile acids Drugs BQ123, dexamethasone, cardiac glycosides, enalapril. fexofenadine, pravastatin Drugs atorvastatin, furosemide, lovastatin, simvastatin... 

Lovastatin is a member of a class of drugs (atorvastatin and simvastatin are others in this class) called statins that are used to treat hypercholesterolemia. The statins act as competitive inhibitors of the enzyme HMG-CoA reductase. These molecules mimic the structure of the normal substrate of the enzyme (HMG-CoA) and act as transition state analogues. While the statins are bound to the enzyme, HMG-CoA cannot be converted to mevalonic acid, thus inhibiting the whole cholesterol biosynthetic process. Recent studies indicate that there may be important secondary effects of statin therapy because some of the medical benefits of statins are too rapid to be a result of decreasing atherosclerotic lesions. Statin therapy has been associated with reduced risks of dementia, Alzheimer disease, ischemic cerebral stroke, and other diseases that are not correlated with high cholesterol levels. Although this is still an active area of research, it appears that the pleiotropic effects of statins may be a result of a reduction in the synthesis of isoprenoid intermediates that are formed in the pathway of cholesterol biosynthesis. 

Site-specific mutated 2-deoxyribose-5-phosphate aldolase (DERA) was used as catalyst for the synthesis of the key intermediate useful for the preparation of the cholesterol lowering drug atorvastatin (Lipitor) (De Santis et al. 2003). 

A space-filling model of the cholesterollowering drug atorvastatin (Lipitor) bound to the active site of its enzyme target HMG-CoA reductase (shown as a yellow surface).The shape of the drug is complementary to the active site of the enzyme. 

Four statin drugs (atorvastatin, lovastatm, pravastatin, and simvastatin) in aqueous samples were determined using L -ESI(+)-MS/MS with methylammonium acetate as an additive in the mobile phase [140]. Protonated atorvastatin, methylammonimn-adducted pravastatin, lovastatin, and simvastatin were selected as precursor ions with a common fragment ion at rtfz 199. All of the statins were detected by L -MS/MS in an untreated sewage influent sample at 4—117 ng/L and in a treated effluent at 1-59 ng/L [140]. 

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