HMG-CoA reductase inhibitors atorvastatin

The G/A promoter polymorphism at the apoAI gene locus predicts individual variability in fasting and postprandial responses to the HMG CoA reductase inhibitor atorvastatin. Circulation 1999 100(Suppl I) I—239. 

Lipid dysfunction HMG-CoA reductase inhibitors Atorvastatin Pfizer/Y amanouchi... 

Chemotherapy Cyclophosphamide, erlotlnlb, ifos-famide, paclitaxel, tamoxifen, vinblastine, vincristine HIV protease inhibitors Amprenavir, atazanavir, indinavir, nelfinavir, ritonavir, saquinavir HMG-CoA reductase inhibitors Atorvastatin, lovastatin, simvastatin... 

Contraindications Concurrent use of a hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (atorvastatin, fluvastatin, lovastatin, pravastatin, or simvastatin) in patients with active hepatic disease or unexplained persistent elevations in serum transaminase levels, moderate or severe hepatic insufficiency... 

Hydroxy-3-Methylgluteryl (HMG)-CoA reductase inhibitors atorvastatin calcium fluvastatin sodium lovastatin pravastatin sodium simvastatin... 

Md.K. Pasha, S. Muzeeb, S.J.S. Basha, D. Shashikumar, R. Mullangi, N.R. Srinivas, Analysis of five HMG-CoA reductase inhibitors—atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin pharmacological, pharmacokinetic and analytical overview and development of a new method for use in pharmaceutical formulations analysis and in vitro metabolism studies, Biomed. Chromatogr. 20 (2006) 282-293. 

Jung KH, Chu K, Jeong SW, Han S Y, Lee ST, Kim JY, Kim M, Roh JK (2004) HMG-CoA reductase inhibitor, atorvastatin, promotes sensorimotor recovery, suppressing acute inflammatory reaction after experimental intracerebral hemorrhage. Stroke 35 1744—1749. 

Bakker-Arkema RG, Davidson MH, Goldstein RJ, et al. Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia. JAMA 1996 275 128-133. 

The ring-opening reaction proceeds with the retention of the absolute configuration at the chiral centers. Thus, (7 )-l-benzyloxy-2,3-epoxypropane was transformed into (i )-l-benzyloxy-4,4-dimethoxybutan-2-ol, which is a useful intermediate for the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors atorvastatin or rosuvastatin (Scheme 6.110) [25]. The... 

Scheme 4.38 Application of the acetate aldol addition of triphenylglycol ester (S)-173 for syntheses of HMG-CoA reductase inhibitors atorvastatin, lovastatin, and fluvastatin.

Lovastati n 1 0, 20, 40 mg tablets 1 0 to 80 mg/day as a single dose (with evening meal) or divided twice daily with food Approximate equivalent doses of HMG-CoA reductase inhibitors are atorvastatin 10 mg, fluvastatin 80 mg, lovastatin 40 mg, pravastatin 40 mg, simvastatin 20 mg, and rosuvastatin 5 mg. 

Atorvastatin Hyperlipidemia HMG-CoA reductase inhibitor, inhibits conversion of HMG-... 

Concomitant lipid-lowering f/ erapy-Atorvastatin may be used in combination with a bile-acid-binding resin for additive effect. Generally, avoid the combination of HMG-CoA reductase inhibitors and fibrates. 

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 be affected by HMG-CoA reductase inhibitors include oral contraceptives, diclofenac, digoxin, glyburide, phenytoin, and warfarin. Atorvastatin, lovastatin, and simvastatin are primarily metabolized by CYP3A4 they may interact with CYP3A4 inhibitors. 

Fluvastatin, launched in 1994, was the first S5mthetic HMG-CoA reductase inhibitor to be approved for the treatment of hypercholesterolemia. This statin was developed by Novartis (Sandoz), and it is marketed as a racemate under the trade name Lescol (Asberg and Holdaas, 2004). In laboratory studies, fluvastatin was shown to potently inhibit HMG-CoA reductase (IC50 = 8 nM) and effectively block cholesterol biosynthesis in hepatoc5de cells (IC50 = 52 nM) (Parker et al., 1990). Clinically, fluvastatin is prescribed less frequently than simvastatin, atorvastatin, or rosuvastatin, but it nevertheless remains an important medication for the treatment of hypercholesterolemia moreover, as the first completely S5mthetic statin to be approved, it offers a compelling synthetic story (Repic et al., 2001). 

HMG CoA reductase inhibitors can be associated with small rises in alanine transaminase activity, but have not been definitely associated with severe morbidity involving altered hepatic function. The results of randomized trials do not suggest that statins in standard doses are hepato-toxic. In none of the large randomized studies in which standard doses were assessed (atorvastatin 10 mg/day, fluvastatin 40-80 mg/day, pravastatin 40 mg/day, simvastatin 20-40 mg/day) was there any clear excess risk of hepatitis or any other serious liver-related adverse events. Long-term large randomized trials have confirmed an excess of persistent rises in transaminases with atorvastatin 80 mg/day compared with lower doses or placebo, and similarly some excess with simvastatin 80 mg/day, but hepatitis and liver failure were not reported (4). 

Black DM, Bakker-Arkema RG, Nawrocki JW. An overview of the clinical safety profile of atorvastatin (Lipitor), a new HMG-CoA reductase inhibitor. Arch Intern Med 1998 158(6) 577-84. 

Bernini F, Poli A, Paoletti R. Safety of HMG-CoA reductase inhibitors focus on atorvastatin. Cardiovasc Drugs Ther 2001 15(3) 211-8. 

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