生物活性

• 描述Atorvastatin inhibits pre-proET-1 mRNA expression in a concentration- and time-dependent fashion (60-70% maximum inhibition) and reduces immunoreactive ET-1 levels (25-50%), this inhibitory effect is maintained in the presence of oxidized LDL (1-50 mg/mL). Atorvastatin significantly reduces angiotensin II-induced and epidermal growth factor-induced ROS production in VSMCs. Atorvastatin downregulates mRNA expression of the NAD(P)H oxidase subunit nox1 in VSMCs, whereas p22phox mRNA expression is not significantly altered. Atorvastatin inhibits membrane translocation of rac1 GTPase, which is required for the activation of NAD(P)H oxidase. Atorvastatin (0.1 μM) significantly diminishes NF-κB activation induced by Ang II and TNF-α in mononuclear cells and VSMC. Atorvastatin (1 μM) diminishes MCP-1 expression induced by Ang II, TNF-α and is reversed by Mevalonate only in Ang II-stimulated cells. Atorvastatin (1 μM) diminishes IP-10 expression induced by Ang II and by TNF-α in VSMC, and this reduction is partially reversed by Mevalonate. Atorvastatin and Gemfibrozil metabolites, but not the parent drugs, are potent antioxidants against lipoprotein oxidation.[1-2]

• 动物研究
  剂量	Rats: 10 mg/kg, max = 20 mg/kg[3]
  给药途径	p.o.
  毒性数据 (半致死量)	Rats: 40 mg/kg p.o.[3]

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00768638	Chronic Kidney Disease	Phase 4	Completed	-	Canada ... more >> Hôtel-Dieu de Québec Hospital Quebec, Canada, G1R2J6 Collapse <<
  NCT02497638	Prostate Cancer	Phase 2	Not yet recruiting	December 2022	Canada, Ontario ... more >> Princess Margaret Cancer Centre Recruiting Toronto, Ontario, Canada, M5G 2M9 Principal Investigator: Robert Hamilton, MD, MPH, FRCSC          Principal Investigator: Neil Fleshner, MD, MPH, FRCSC Collapse <<
  NCT00974740	Type 1 Diabetes	Phase 1	Terminated(for lack of recruit... more >>ment) Collapse <<	-	Germany ... more >> Diabetes-Zentrum Mergentheim Bad Mergentheim, Germany, 97980 Gemeinschaftskrankenhaus Havelhöhe Berlin, Germany, 14089 Helios Klinikum Emil von Behring Berlin, Germany, 14165 Praxis Dr. Friedhelm Schmitten Bestwig-Ramsbeck, Germany, 59909 DDZ Deutsches Diabetes Zentrum Düsseldorf, Germany, 40221 St. Josefs Krankenhaus Heidelberg, Germany, 69115 St. Antonius Krankenhaus, Med. Klinik Köln, Germany, 50968 Praxisklinik Leipzig Leipzig, Germany, 04103 Praxis Dr. Gerhard Willms Leverkusen, Germany, 51373 Praxis Dr. Heinz-Georg Ley Marl, Germany, 45770 Diabetologische Schwerpunktpraxis, Angiologie Münster, Germany, 48145 Praxis Dr. Werner Stürmer Würzburg, Germany, 97070 Collapse <<

• 更多
• 参考文献

• [1] Colhoun HM, Betteridge DJ, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364(9435):685-96.

  [2] Zhang L, He H, Balschi JA. Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration. Am J Physiol Heart Circ Physiol. 2007;293(1):H457-66.

  [3] Crespo MJ, Quidgley J. Simvastatin, atorvastatin, and pravastatin equally improve the hemodynamic status of diabetic rats. World J Diabetes. 2015;6(10):1168-78.