生物活性

• 描述The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA ) reductase is the rate-limiting enzyme involved in the multistep synthesis of cholesterol. Pitavastatin is a fully synthetic competitive inhibitor of HMG-CoA reductase^[4]. Pitavastatin Calcium (NK-104 hemicalcium) inhibits cholesterol synthesis from acetic acid with an IC50 of 5.8 nM in HepG2 cells. Pitavastatin Calcium inhibits the growth of a panel of ovarian cancer cells, including those considered most likely to represent high-grade serous ovarian cancer (HGSOC), grown as a monolayers (IC50 = 0.4-5 μM) or as spheroids (IC50=0.6-4 μM). Pitavastatin Calcium (1 μM; 48 hours ) induces apoptosis, evidenced by the increased activity of executioner caspases-3,7 as well as caspase-8 and caspase-9 in Ovcar-8 cells and Ovcar-3 cells. Pitavastatin (1 μM, 48 hours) caused PARP cleavage in Ovcar-8 cells. Pitavastatin Calcium (59 mg/kg; p.o.; twice daily for 28 days) caused significant tumour regression ^[5]. EL mRNA expression was inhibited after treatment with pitavastatin for 6 h, and maximal inhibition occurred and reached plateau after treatment for 24 h. The plasma levels of total cholesterol in mice treated with pitavastatin or vehicle were 2.04+0.15 and 2.18+0.23 mmol/L, respectively(n.s.). The plasma HDL-C levels in mice with or without pitavastatin were 1.87+0.11 and 2.02+0.22 mmol/L, respectively (n.s.). EL expression in vivo through the Rho signalling pathway, and the effect was irrespective of the plasma cholesterol levels^[6].
• 作用机制Pitavastatin increased the mRNA levels of CYP7A1 in HepG2 cells, suggesting that increased conversion of cholesterol to bile acids may be the mechanism for its potent low-density lipoprotein cholesterol-lowering effects^[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
  NCT03418974	Dyslipidemias	Phase 4	Active, not recruiting	December 31, 2021	China, Beijing ... more >> Heart Center of Peking University People's Hospital Beijing, Beijing, China, 100044 China, Shanghai School of Public Health, Fudan University Shanghai, Shanghai, China, 200032 Collapse <<
  NCT01178853	-	-	Completed	-	-
  NCT00242944	Coronary Disease ... more >> Hypercholesterolemia Collapse <<	Phase 4	Completed	-	Japan ... more >> Juntendo University School of Medicine Bunkyo-ku, Tokyo, Japan, 113-8421 Yamaguchi University Graduate School of Medicine Ube, Yamaguchi, Japan, 755-8505 Kyoto University Graduate School of Medicine Kyoto, Japan, 606-8507 Collapse <<

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• 参考文献

• [1] Ahmad H, Cheng-Lai A. Pitavastatin: a new HMG-CoA reductase inhibitor for the treatment of hypercholesterolemia. Cardiol Rev. 2010 Sep-Oct;18(5):264-7.

  [2] Maejima T, Yamazaki H, et al. Effect of pitavastatin on apolipoprotein A-I production in HepG2 cell. Biochem Biophys Res Commun. 2004 Nov 12;324(2):835-9.

  [3] Ping Fan,et al. Circ J. Pitavastatin, a potent hydroxymethylglutaryl coenzyme a reductase inhibitor, increases cholesterol 7 alpha-hydroxylase gene expression in HepG2 cells2004 Nov;68(11):1061-6.

  [4] Igel M, Sudhop T, von Bergmann K. Pharmacology of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), including rosuvastatin and pitavastatin. J Clin Pharmacol 2002;42:835-45

  [5] Elizabeth de Wolf,et al. Dietary geranylgeraniol can limit the activity of pitavastatin as a potential treatment for drug-resistant ovarian cancer. Sci Rep. 2017 Jul 14;7(1):5410.

  [6] Yoko Kojima，et al. Pitavastatin decreases the expression of endothelial lipase both in vitro and in vivo.Cardiovasc Res.2010 Jul 15;87(2):385-93.

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