Rosuvastatin (ZD4522) and pitavastatin (NK-104) are novel HMG-CoA reductase inhibitors with a peculiar pharmacological profile. In particular, they show a high potency in decreasing LDL-C and their catabolism is not mediated by the cytochrome P-450 3A4, thus reducing the potential for drug-drug interaction and improving the management of blood cholesterol. As the magnitude of LDL-C reduction is directly associated with the decrease in the incidence of myocardial infarction and mortality for CAD, statins with increased LDL-C lowering potency may ensure the achievement of target LDL-C levels and offer a more aggressive cholesterol control, further improving CAD morbidity and mortality. 相似文献
AIM: Lipid lowering therapy with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors is increasingly used for the prevention of cardiovascular events, but they should be used with caution in patients with impaired liver function. We therefore studied the pharmacokinetics of pitavastatin in patients with liver cirrhosis. METHODS: Plasma concentrations of pitavastatin were determined after administration of 2 mg single-dose pitavastatin to 12 male patients with liver cirrhosis (six Child-Pugh grade A and six grade B). These results were compared with the single-dose pharmacokinetic results obtained from six male volunteers without liver disease. RESULTS: Administration of 2 mg single-dose pitavastatin to patients with Child-Pugh grade A and grade B cirrhosis resulted in a 1.19- and 2.47-fold increase in Cmax and 1.27- and 3.64-fold increase in AUCt, respectively, when compared with normal subjects. The geomean Cmax of pitavastatin was 59.5 ng ml(-1), 70.7 ng ml(-1) and 147.1 ng ml(-1) in the control, Child-Pugh grade A and Child-Pugh grade B groups, respectively. The geomean AUCt of pitavastatin in the three groups was 121.2 ng h(-1) ml(-1), 154.2 ng h(-1) ml(-1) and 441.7 ng h(-1) ml(-1), respectively. The geomean Cmax of pitavastatin lactone was 20.3 ng ml(-1), 19.1 ng ml(-1) and 9.9 ng ml(-1) in the control, Child-Pugh grade A and grade B groups, respectively. The AUCt of pitavastatin lactone was 120.2 h(-1) ml(-1), 108.8 h(-1) ml(-1) and 87.5 h(-1) ml(-1), respectively. CONCLUSION: The plasma concentration of pitavastatin is increased in patients with liver cirrhosis. In such patients, caution is required, although dose reduction may not be necessary in Child-Pugh A cirrhosis. 相似文献
Introduction: Statins are the first line of therapy to reduce low-density lipoprotein cholesterol (LDL-C) in order to decrease cardiovascular events. Pitavastatin is the latest statin to be introduced to the market.
Areas covered: In this article, the authors review the efficacy, safety, and tolerability of pitavastatin. The authors also review a recent cardiovascular outcome study.
Expert opinion: Pitavastatin produces dose-dependent reductions in LDL-C at lower doses than other statins. The maximum approved dose of 4 mg reduces LDL-C by about 40–49% in different patient groups and is equivalent to atorvastatin 20 mg in this effect. Pitavastatin undergoes minimal metabolism so drug–drug interactions are less likely than with many other statins, but it can interact with some drugs that inhibit drug transporters. Compared with other statins, it has been associated with greater increases in high-density lipoprotein cholesterol and it was found to be less likely to cause new onset diabetes. In a recent study in Japanese patients with stable coronary artery disease, pitavastatin 4 mg was more effective than pitavastatin 1 mg in reducing cardiovascular events. Therefore, the highest dose may be preferred in high-risk patients. 相似文献
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are established first line treatments for hypercholesterolaemia. In addition to the direct effects of statins in reducing concentrations of atherogenic low density lipoprotein cholesterol (LDL-C), several studies have indicated that the beneficial effects of statins may be due to some of their cholesterol-independent, multiple (pleiotropic) effects which may differ between different members of the class. Pitavastatin is a novel synthetic lipophilic statin that has a number of pharmacodynamic and pharmacokinetic properties distinct from those of other statins, which may underlie its potential pleiotropic benefits in reducing cardiovascular risk factors. This review examines the principal pleiotropic effects of pitavastatin on endothelial function, vascular inflammation, oxidative stress and thrombosis. The article is based on a systematic literature search carried out in December 2010, together with more recent relevant publications where appropriate. The available data from clinical trials and in vitro and animal studies suggest that pitavastatin is not only effective in reducing LDL-C and triglycerides, but also has a range of other effects. These include increasing high density lipoprotein cholesterol, decreasing markers of platelet activation, improving cardiac, renal and endothelial function, and reducing endothelial stress, lipoprotein oxidation and, ultimately, improving the signs and symptoms of atherosclerosis. It is concluded that the diverse pleiotropic actions of pitavastatin may contribute to reducing cardiovascular morbidity and mortality beyond that achieved through LDL-C reduction. 相似文献