Disease relevance of Livalo

• The effect of compound NK-104 was studied, a new competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA-reductase), on apo B-100 synthesis and secretion from the human hepatoma cell line Hep G2 [1].
• Six-month repeated oral toxicity study of NK-104 in rats [2].

High impact information on Livalo

• NK-104, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, reduces osteopontin expression by rat aortic smooth muscle cells [3].
• NK-104, a potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, decreases apolipoprotein B-100 secretion from Hep G2 cells [1].
• These results indicate that NK-104 and simvastatin at 10 times the dosage of the former, similarly enhances hepatic LDL receptor; however, only NK-104 with prolonged action suppresses VLDL secretion to show higher cholesterol-lowering potency and triglyceride-reducing effect [4].
• In the present study, we examined the effect of pitavastatin (NK-104), a synthetic statin (3-hydroxy-3-methylglutaryl CoA reductase inhibitor), on IL-8 production induced by CRP in human AoEC (aortic endothelial cells) [5].
• These results suggest that NK-104 exerts its hypotriglyceridemic action, primarily by diverting the exogenous free fatty acid to the pathways of oxidation at the expense of esterification [6].

Chemical compound and disease context of Livalo

• NK-104, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, was administered orally to Wistar rats at a dose of 2, 10, 50 or 100 mg/kg for 28 days consecutively, and the toxicity of NK-104 and its recovery with 2 weeks cessation of drug treatment were examined [7].

Biological context of Livalo

• These findings suggest that NK-104 suppresses balloon-injury-induced neointimal thickening through inhibition of intimal smooth muscle cell growth and extracellular matrix accumulation [8].
• NK-104 suppressed the intimal total and Br-dU-labeled cell number [8].
• Biotransformation profiles of NK-104 in bile from rat, rabbit and dog given an intravenous infusion of NK-104 were investigated [9].
• Plasma sample was extracted with methyl tert-butyl ether and then the extract was subjected to methylation with diazomethane to prevent the mutual conversion between NK-104 and its lactone [10].
• When cells were treated with a 200-fold excess of the IC50 concentration of each inhibitor, NK-104 was able to induce LDL receptor mRNA most effectively [11].

Anatomical context of Livalo

• NK-104 showed marked inhibition in liver (ED50 0.13 mg/kg) and in ileum (ED50 0.20 mg/kg), but much weaker in the other tissues [12].
• Liver endoplasmic reticulum (ER) was isolated and measured for lipid content and activity of ER enzymes (NK-104: 3 mg/kg, SV: 30 mg/kg) [13].
• NK-104 decreased the surface lesion area at the arch (23.1%, p = 0.054) and reduced the degeneration of media in the thoracic aorta (69.9% increase in medial smooth muscle cells, p < 0.01) [14].
• There was no inhibitory effect of NK-104 on CYP-mediated metabolism of taxol in human liver microsomes [15].

Associations of Livalo with other chemical compounds

• There was a dose-dependent and significant reduction of both plasma total cholesterol (17.4, 24.5 and 45.3% at 0.3, 1 and 3 mg/kg, respectively) and triglycerides (21.1 and 32.2% at 1 and 3 mg/kg, respectively) after 14-day administration of NK-104 [4].
• Rosuvastatin (ZD4522) and pitavastatin (NK-104) are novel HMG-CoA reductase inhibitors with a peculiar pharmacological profile [16].
• Pitavastatin (CAS 147526-32-7, NK-104) is a new and very potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and has been approved for treatment of hyperlipoproteinaemia [17].
• The kinetic study, using rat liver microsomal HMG-CoA reductase, revealed that NK-104 is a competitive inhibitor of HMG-CoA reductase with a Ki of 1.7 nmol/l. To examine the inhibitory effect on sterol synthesis in vivo, de novo synthesis of sterols from [14C]acetate 3 h after oral administration of NK-104 was measured in rats [12].

Gene context of Livalo

• The LDL receptor mRNA was induced by NK-104 most effectively between 0.1 to 10 microM among the lipophilic inhibitors, whereas the degrees of induction of HMG-CoA reductase mRNA by these inhibitors did not differ significantly from each other [11].
• Functional interplay between the macrophage scavenger receptor class B type I and pitavastatin (NK-104) [18].
• Here, we investigated the effects of pitavastatin (NK-104), a newly synthesized statin, on macrophage SR-BI expression [18].
• On coincubation with several fibrates, pitavastatin (CAS 147526-32-7) did not displace fibrates from their protein binding in human plasma [19].
• The TG content in ER and activity of diacylglycerol acyltransferase of ER, increased with SV and slightly with NK-104 [13].

Analytical, diagnostic and therapeutic context of Livalo

• The proposed method has been applied to plasma samples obtained after oral administration of a single 2 mg dose of NK-104 to volunteers [10].
• Simultaneous determination of NK-104 and its lactone in biological samples by column-switching high-performance liquid chromatography with ultraviolet detection [10].
• A simple and sensitive column-switching HPLC method has been developed for the simultaneous determination of NK-104 (HMG-CoA reductase inhibitor) and its lactone in human and dog plasma [10].
• Simultaneous determination of taxol and its metabolites in microsomal samples by a simple thin-layer chromatography radioactivity assay--inhibitory effect of NK-104, a new inhibitor of HMG-CoA reductase [15].

References