Disease relevance of cerivastatin

• Indeed, pharmacokinetic interactions (e.g. increased bioavailability), myositis, and rhabdomyolysis have been reported following concurrent use of atorvastatin, cerivastatin, simvastatin or lovastatin and cyclosporine A, mibefradil or nefazodone [1].
• However, simvastatin, lovastatin, cerivastatin and atorvastatin are biotransformed in the liver primarily by cytochrome P450 (CYP) 3A4, and clinical experience has shown that the risk of adverse effect, such as myopathy, increases with concomitant use of statins with drugs that substantially inhibit CYP 3A4 at therapeutic doses [1].
• Cerivastatin diminished accumulation of macrophages in aortic atheroma [2].
• Here, we show that lipophilic statins (atorvastatin, simvastatin, cerivastatin) markedly induce caspases-dependent apoptosis in various human osteosarcoma cells, independently of bone morphogenetic protein (BMP)-2 signaling and cell differentiation [3].
• CONCLUSIONS: Short-term lipid-lowering therapy with cerivastatin can improve endothelial function and NO bioavailability after two weeks in patients with hypercholesterolemia [4].

Psychiatry related information on cerivastatin

• However, cerivastatin improves endothelial dysfunction, possesses anti-inflammatory, antioxidant, anticoagulant, antithrombotic, antiproliferative, plaque-stabilizing, immunmodulatory, and angiogenic effects, and may even prevent tumor growth, Alzheimer's disease, and osteoporosis [5].

High impact information on cerivastatin

• Cerivastatin was the most commonly implicated statin [6].
• Cerivastatin-induced rhabdomyolysis [7].
• An HMG-CoA reductase inhibitor, cerivastatin, suppresses growth of macrophages expressing matrix metalloproteinases and tissue factor in vivo and in vitro [2].
• Cerivastatin reduced the number of macrophages expressing histone mRNA (a sensitive marker of cell proliferation) detected by in situ hybridization but did not alter macrophages bearing a marker of death (TUNEL staining) [2].
• Cerivastatin treatment (>or=0.01 micromol/L) also reduced growth, proteolytic activity due to MMP-9, and TF expression in cultured human monocyte/macrophages [2].

Chemical compound and disease context of cerivastatin

• Combination therapy with cerivastatin and gemfibrozil causing rhabdomyolysis: is the interaction predictable [8]?
• CONCLUSION/INTERPRETATION: In this hypertensive model of diabetic nephropathy, cerivastatin decreased albuminuria through suppression of glomerular hyperfiltration, mesangial expansion, and the loss of charge barrier independently of a cholesterol-lowering effect [9].
• AIMS/HYPOTHESIS: We investigated the effect of cerivastatin, a statin, on the development of diabetic nephropathy in spontaneously hypertensive rats (SHR) with streptozotocin-induced diabetes [9].
• We investigated mitochondrial toxicity of four lipophilic stains (cerivastatin, fluvastatin, atorvastatin, simvastatin) and one hydrophilic statin (pravastatin) [10].
• As with other HMG-CoA reductase inhibitors, rare reports of myopathy and rhabdomyolysis have occurred with cerivastatin, although gemfibrozil or cyclosporin were administered concomitantly in most cases [11].

Biological context of cerivastatin

• Endothelium-dependent vasodilation improved in comparison with placebo (ACh 48 microg/min: +203 +/- 85% [cerivastatin] vs. -26 +/- 71% [placebo], p < 0.05) [4].
• Cerivastatin reduced the 3H-thymidine incorporation (164 +/- 11%, p < 0.01), inhibited Cdk2 activation and Rb phosphorylation, but did not prevent p27Kip1 down-regulation, nor p42mapk and p70S6K activation [12].
• Furthermore, cerivastatin inhibited protein prenylation in osteoclasts isolated from the rabbit bone marrow of rabbits after treatment in vivo [13].
• Cerivastatin inhibited TGF-beta(1) gene upregulation by 25% [14].
• The effects of cerivastatin were abolished by NOS inhibition in the CLH group (CO at 12 weeks: 69.3 +/- 2.8 ml/min, p < 0.05 vs. C). CONCLUSIONS: Left ventricular remodeling was profoundly changed by statin treatment [15].

Anatomical context of cerivastatin

• OBJECTIVES: This study examined effects of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitor cerivastatin on human saphenous vein (SV), endothelial cells (EC) and smooth muscle cells (SMC) [12].
• Effects of cerivastatin on urinary albumin excretion, mesangial expansion, glomerular macrophage infiltration, and the number of anionic sites on the glomerular basement membrane (GBM) were assessed [9].
• Cerivastatin is at least 10 times more potent than the other statins at inducing apoptosis in AML cell lines [16].
• The cerivastatin-induced effects on monocyte functions could explain, at least in part, the protective effect of this drug against atherothrombotic events [17].
• OBJECTIVE: We investigated the effects of the statins, cerivastatin and fluvastatin, on the induction of nitric oxide (NO) production in vascular smooth muscle cells (VSMC) stimulated by interleukin-1beta (IL-1) or in combination with interferon-gamma (IFN) [18].

Associations of cerivastatin with other chemical compounds

• Mevalonate abrogated the effects of cerivastatin on Cdk2 and Rb but only partially rescued the 3H-thymidine incorporation (from 164 +/- 11% to 211 +/- 13%, n = 4, p < 0.01) [12].
• In the present study, we evaluated the relative potency and mechanism of action of the newer synthetic statins, fluvastatin, atorvastatin, and cerivastatin, to trigger tumor-specific apoptosis [16].
• Our aim was to study the effect of gemfibrozil on cerivastatin pharmacokinetics [19].
• This suggests protein geranylgeranylation is an essential downstream component of the mevalonate pathway for cerivastatin similar to lovastatin-induced apoptosis [16].
• CONCLUSIONS: Cerivastatin and metabolites plasma concentrations were significantly increased in kidney transplant recipients treated with cyclosporine and other immunosuppressive agents [20].

Gene context of cerivastatin

• Cerivastatin is metabolized by cytochrome P450 (CYP)3A4 and CYP2C8 [21].
• IL-6 levels decreased significantly in the fenofibrate group (39%; p <0.0001), but not in the cerivastatin group (15%; p = 0.24) No significant decreases were observed for TNF-alpha [22].
• However, with cerivastatin (CVA), the glucuronidation as well as the CYP2C8- and CYP3A4-mediated oxidation pathways were much more susceptible to inhibition by GFZ than was observed with SVA or AVA [23].
• The effects of the statins lovastatin and cerivastatin on signalling by the prostanoid IP-receptor [24].
• HMG-CoA reductase inhibitors such as cerivastatin would be useful to study for elucidating molecular and cellular mechanisms of hCAR [25].

Analytical, diagnostic and therapeutic context of cerivastatin

• In a double-blind, placebo-controlled, randomized crossover study, 15 stable mild hyperglycemic patients without treatment and with features of metabolic syndrome were treated with cerivastatin (0.4 mg/day) or placebo for 3 months [26].
• At 1.0 mg/kg, cerivastatin inhibited the diabetes-induced expansion of mesangial and tuft areas on histological examination of the kidneys, as well as the loss of anionic sites from the GBM evaluated with polyetyleneimine and the intraglomerular infiltration of ED1-positive macrophages evaluated by immunohistochemistry [9].
• Cyclosporine steady-state concentration-time profiles were determined in blood with monoclonal (EMIT [enzyme multiplied immunoassay technique] assay, parent drug specific) and polyclonal antibodies (FPIA [fluorescence polarization immunoassay] assay, cyclosporine plus metabolites) during cerivastatin cotreatment and compared with predosing data [20].
• The overall incidence and nature of adverse events reported with cerivastatin in clinical trials was similar to that of placebo [11].
• METHODS: The effects of cerivastatin on skeletal reconstruction by vascularized bone allograft were investigated in a rat tibia-fibula graft model [27].

References