Rosuvastatin

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Rosuvastatin, also known as Crestor

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Pharmacokinetics

Statin Pharmacokinetics at 10mg Dosage
Parameter Atorvastatin (Lipitor) Fluvastatin (Lescol) Lovastatin (Mevacor) Simvastatin (Zocor) Rosuvastatin (Crestor) Cerivastatin (Baycol)
Tmax (hr) 2.5 1 3 1.5 4 1.5
Cmax (ng/ml) 27-66 448 10-20 7.3 4.34 3.43
Bioavailability (%) 12 19-29 5 5 20 60
Protein Binding (%) 80-90 99 95 95 88 99
T1/2 (hr) 15-30 2 3 2.7 19 2.2
AUC (ng/ml/hr) 104 ~150 33 125 48 14.5
IC50 (nM) 154 198 800 66 320 50-90
Equivalent LDL Reduction Dosage (mg) 10 -- 80 20 5 --
Metabolism Hepatic
(CYP3A4) 		Hepatic
(CYP2C9) 		Hepatic
(CYP3A4) 		Hepatic
(CYP3A4) 		None Hepatic
(CYP2C8)

For References, See References

Effectiveness and Side Effects

Effectiveness

Rosuvastatin has the greatest efficacy compared to other statins at the same dosage. At 5mg, patients experienced a 40% or greater reduction in LDL as compared to similar results for Atorvastatin at 20mg doses. [4]

Side Effects

Although all of the statins are generally considered safe, rosuvastatin had a higher reported adverse event rate than other statin clinical trials. Typical adverse events include muscle weakness, headache dizziness and slightly increased creatinine kinase (CK) levels (an indication of kidney and smooth muscle damage), although these are common to all the statins (with the exception of elevated CK levels which only occurs in Atorvastatin, Rosuvastatin, and Simvastatin)[5]

Interesting Facts

  • Rosuvastatin has made recent headlines as being nearly equivalent in efficacy to Lipitor, but also cuts the rate of heart attacks and strokes significantly. [6]
  • Unlike other statins, consuming grapefruit juice does not affect the PKs of rosuvastatin. [7] [8]
  • Studies have reveal that that Asians appear to process rosuvastatin differently than members of other races with Cmax and AUC reaching levels which were over 2 fold greater. The FDA has subsequently announced that asians should take half the standard dose to achieve the same cholesterol lowering benefit. [9]

The Jist

The statins are generally viewed as very safe and have been proven effective over the past 15 years. Rosuvastatin is the newest major blockbuster statin and was designed to be taken at lower levels than other statins. Recent studies have indicated rosuvastatin can reduce the likely hood of myocardial infarction and stroke, although this has been refuted by some studies. Truth be told, with major statins like Lipitor coming off patent in the next year or two, pharmaceutical companies are looking for new diseases that can be treated by still-patented statins like Rosuvastatin (Patent expires in 2016). With $4 billion in sales per year and Lipitor going off patent in 2011, resulting in a dramatic price drop in statins as generics flood the market, proving that Rosuvastatin reduces heart attacks, etc. would be worth many billions of dollars. It remains to be seen whether the potential reduction in heart ailments while taking Rosuvastatin, if it exists, can be proven with statistical significance.

References

  1. ↑ http://www.reuters.com/article/idUSN2223558720100222
  2. ↑ Istvan ES, Deisenhofer J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science. 2001 May 11;292(5519):1160-4. PMID:11349148 doi:10.1126/science.1059344
  3. ↑ Corsini A, Maggi FM, Catapano AL. Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacol Res. 1995 Jan;31(1):9-27. PMID:7784310
  4. ↑ Weng TC, Yang YH, Lin SJ, Tai SH. A systematic review and meta-analysis on the therapeutic equivalence of statins. J Clin Pharm Ther. 2010 Apr;35(2):139-51. PMID:20456733 doi:10.1111/j.1365-2710.2009.01085.x
  5. ↑ Weng TC, Yang YH, Lin SJ, Tai SH. A systematic review and meta-analysis on the therapeutic equivalence of statins. J Clin Pharm Ther. 2010 Apr;35(2):139-51. PMID:20456733 doi:10.1111/j.1365-2710.2009.01085.x
  6. ↑ Everett BM, Glynn RJ, MacFadyen JG, Ridker PM. Rosuvastatin in the prevention of stroke among men and women with elevated levels of C-reactive protein: justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER). Circulation. 2010 Jan 5;121(1):143-50. Epub 2009 Dec 21. PMID:20026779 doi:10.1161/CIRCULATIONAHA.109.874834
  7. ↑ Kantola T, Kivisto KT, Neuvonen PJ. Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther. 1998 Apr;63(4):397-402. PMID:9585793 doi:10.1016/S0009-9236(98)90034-0
  8. ↑ Ohta T, Nagahashi M, Hosoi S, Tsukamoto S. Dihydroxybergamottin caproate as a potent and stable CYP3A4 inhibitor. Bioorg Med Chem. 2002 Apr;10(4):969-73. PMID:11836106
  9. ↑ Lee E, Ryan S, Birmingham B, Zalikowski J, March R, Ambrose H, Moore R, Lee C, Chen Y, Schneck D. Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment. Clin Pharmacol Ther. 2005 Oct;78(4):330-41. PMID:16198652 doi:10.1016/j.clpt.2005.06.013


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