NK-104: a novel synthetic HMG-CoA reductase inhibitor

Expert Opin Investig Drugs. 2000 Nov;9(11):2653-61. doi: 10.1517/13543784.9.11.2653.


An elevated level of low-density lipoprotein (LDL)-cholesterol has been recognised as the most important risk factor for coronary artery disease (CAD). Development of the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) ('statins'), a rate-limiting key enzyme of cholesterol synthesis pathway, has revolutionised the cholesterol-lowering therapy. In the last decade, effective primary and secondary preventive measures have been established in several statin trials to prevent future events of CAD by lowering LDL-cholesterol levels. These results supported the 'lower is better' hypothesis in the relationship between LDL-cholesterol levels and CAD. NK-104 (pitavastatin, previously named as itavastatin or nisvastatin, Kowa Company Ltd., Tokyo) has recently been developed as a new chemically synthesised and powerful statin. On the basis of reported data, the potency of NK-104 is dose-dependent and appears to be equivalent to that of atorvastatin. This new statin is safe and well-tolerated in the treatment of patients with hypercholesterolaemia. The cytochrome P450 system only slightly modifies NK-104, which suggests the clinical advantage of this agent, because the prevalence of clinically significant interactions with a number of other commonly used drugs can be considered to be extremely low. NK-104 can provide a new and potentially superior therapeutic agent when compared with currently available other statins. Randomised controlled clinical trials to assess the long-term effects of this new statin on CAD would be required.

Publication types

  • Review

MeSH terms

  • Animals
  • Arteriosclerosis / prevention & control
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy
  • Lipid Metabolism*
  • Lipids / blood
  • Quinolines / adverse effects
  • Quinolines / pharmacokinetics
  • Quinolines / pharmacology
  • Quinolines / therapeutic use*
  • Randomized Controlled Trials as Topic


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Quinolines
  • pitavastatin