Cerivastatin

Cerivastatin 7 (Figure 7), another entirely synthetic statin, is one of the most potent inhibitors of HMG-CoA reductase (Ki = 1.3 pM) identified.66 Cerivastatin contains a unique penta-substituted pyridine core, retains the unsaturated E-heptenoic acid side chain with the identical (3R, 5S) chirality found in fluvastatin, and is about 100-fold more potent than lovastatin. Cerivastatin was orally active in animal models in the low mgkg— 1 range. For example, in normal chow-fed dogs, oral cerivastatin at 0.01-0.1 mg kg— 1 day— 1 dose-dependently reduced LDLc plasma levels after 18 days, and this reduction reached a maximum of 75% with the 0.1 mgkg — 1 day— 1 dose. Similarly, low oral daily doses of 0.1 mgkg — 1 of cerivastatin reduced plasma LDLc and the progression of atherosclerosis in rabbit models after 9 weeks of dosing.

The lower doses of cerivastatin administered in animal studies were also effective in humans where, at daily doses of 0.025-0.4 mg, cerivastatin reduced LDLc levels dose-dependently and by greater than 50% using the 0.4 mg daily dose. Cerivastatin has a much higher overall oral bioavailability (~ 60%) than other statins and is metabolized in humans by both CYP3A4 and CYP2C8. Like many other statins, it is highly protein-bound (>95%), in spite of its fairly low ClogP (1.5). Cerivastatin 7 was first approved for human use in the UK in 1997. It was voluntarily withdrawn in 2001 after higher incidences of severe myopathy and renal failure were observed in cerivastatin-treated patients, particularly in patients co-treated with gemfibrozil.

Was this article helpful?

0 0
Diabetes Sustenance

Diabetes Sustenance

Get All The Support And Guidance You Need To Be A Success At Dealing With Diabetes The Healthy Way. This Book Is One Of The Most Valuable Resources In The World When It Comes To Learning How Nutritional Supplements Can Control Sugar Levels.

Get My Free Ebook


Post a comment