Pravastatin drug

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

The cholesterol-lowering agents called statins, such as simvastatin (Zocor) and pravastatin (Pravachol), are among the most widely prescribed drugs in the world. Identify the functional groups in both, and tell how the two substances differ. 

Scheme 6.17 gives some examples of the orthoamide and imidate versions of the Claisen rearrangement. Entry 1 applied the reaction in the synthesis of a portion of the alkaloid tabersonine. The reaction in Entry 2 was used in an enantiospecific synthesis of pravastatin, one of a family of drugs used to lower cholesterol levels. The product from the reaction in Entry 3 was used in a synthesis of a portion of the antibiotic rampamycin. Entries 4 and 5 were used in the synthesis of polycyclic natural products. Note that the reaction in Entry 4 also leads to isomerization of the double bond into conjugation with the ester group. Entries 1 to 5 all involve cyclic reactants, and the concerted TS ensures that the substituent is introduced syn to the original hydroxy substituent. 

With the exception of pravastatin which is mainly metabolized by isomerization in the gut to a relatively inactive metabolite, the other statins undergo biotransformation by the cytochrome P-450 system. Therefore, drugs known to inhibit statin metabolism should be used cautiously. The time until maximum effect on lipids for statins is generally 4 to 6 weeks. 

Yamazaki, M., Tokui, T., Ishigami, M., Sugiyama, Y., Tissue-selective uptake of pravastatin in rats contribution of a specific carrier-mediated uptake system, Biopharm. Drug Dispos. 1996, 17, 775-789. 

Ni inuma, K., Nishigaki, R., Sugiyama Y., Biliary excretion of pravastatin in rats contribution of the excretion pathway mediated by canalicular multispecific organic anion transporter, Drug Metab. Dispos. 1997, 25, 1123-1129. 

Pravastatin study, 91 Preclinical drug development, 154 Predictive values, 106 reduced, 171-175... 

Baycol (cerivastatin, sold as Lipobay in Europe, Bayer) is a statin, a class of cholesterol-lower drugs. Statins are the most prescribed drugs in the United States, with more than 12 million people taking them, and more than 700,000 people in the United States taking cerivastatin. It received marketing approval on June 26, 1997 and was voluntarily removed from the market on August 8, 2001 because of its link to 100 deaths and several injuries from potentially the muscle disease rhabdomyolysis. The other statins — lovas-tatin (Mevacor Merck) pravastatin (Pravachol Bristol-Myers Squibb) simvastatin (Zocor Merck) fluvastatin (Lescol Novartis) atorvastatin (Lipitor Parke-Davis) rosuvastatin... 

The statins, e.g. pravastatin, are a group of HMGR inhibitors that possess functionalities that mimic the half-reduced substrate mevaldate hemithioacetal. The affinity of these agents towards HMG-CoA reductase is some 10" -fold more than the natural substrate, making them extremely effective inhibitors of the enzyme, and powerful drugs in coronary care. 

Concomitant immunosuppressants- In patients taking immunosuppressive drugs such as cyclosporine concomitantly with pravastatin, begin therapy with pravastatin 10 mg once/day at bedtime and titrate to higher doses with caution. Most patients treated with this combination received a maximum pravastatin dose of 20 mg/day. 

Endocrine effects Statins interfere with cholesterol synthesis and lower circulating cholesterol levels and, as such, might theoretically blunt adrenal or gonadal steroid hormone production. Small declines in total testosterone with no commensurate elevation in LH have been noted with the use of fluvastatin. Pravastatin showed inconsistent results with regard to possible effects on basal steroid hormone levels atorvastatin, lovastatin, rosuvastatin, and simvastatin did not reduce basal plasma cortisol concentration or basal plasma testosterone concentration or impair adrenal reserve. Appropriately evaluate patients who display clinical evidence of endocrine dysfunction. Exercise caution when administering HMG-CoA reductase inhibitors with drugs that affect steroid levels or activity, such as ketoconazole, spironolactone, and cimetidine. 

Drugs that may interact with orlistat include cyclosporine, fat-soluble vitamins, pravastatin, and warfarin. 

Increases in exposure were reported for atorvastatin (84,154), lovastatin (155,156), and simvastatin (85,87,157). GFJ was shown not to have an effect on the pharmacokinetics of pravastatin (84,154). Atorvastatin exhibited a moderate interaction with GFJ regarding the overall exposure. Lovastatin and simvastatin exhibited a strong interaction. Pravastatin could be chosen as an alternative drug if patients want to ensure a lack of interaction. 

The catabolism of lovastatin, simvastatin, and atorvastatin proceeds chiefly through CYP3A4, whereas that of fluvastatin and rosuvastatin is mediated by CYP2C9. Pravastatin is catabolized through other pathways, including sulfation. The 3A4-dependent reductase inhibitors tend to accumulate in plasma in the presence of drugs that inhibit or compete for the 3A4 cytochrome. These include the macrolide antibiotics, cyclosporine, ketoconazole and its congeners, HIVprotease inhibitors, tacrolimus, nefazodone, fibrates, and others (see Chapter 4). Concomitant use of reductase inhibitors with amiodarone or verapamil also causes an increased risk of myopathy. 

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