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Pleiotropic effects of pitavastatin.

Davignon J - Br J Clin Pharmacol (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montréal (IRCM) and University of Montréal, QC, Canada. Jean.Davignon@ircm.qc.ca

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Molecular structures of (A) HMG-CoA and (B) hydrophilic and (C) lipophilic currently available statins. Adapted from Shitara et al. [126]
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fig01: Molecular structures of (A) HMG-CoA and (B) hydrophilic and (C) lipophilic currently available statins. Adapted from Shitara et al. [126]

Mentions: Statins may be broadly divided into two categories, according to their solubility (Figure 1). Pravastatin and rosuvastatin possess polar side groups attached to hydrophobic ring structures, rendering them hydrophilic, while pitavastatin, atorvastatin, fluvastatin, lovastatin and simvastatin do not, and are consequently classed as lipophilic [2]. Furthermore, the differing chemical structures of individual statins substantially alter the way these molecules are taken up by the liver and catabolized or excreted. Lovastatin and simvastatin, for example, circulate as an inactive, lactone prodrug [13], while atorvastatin and rosuvastatin are biologically active as calcium salts [14, 15]. Rates of biliary excretion, involving a number of transporters, such as breast cancer resistance protein and multidrug resistance-associated protein 2 [16], and hepatic uptake by various transporting polypeptides, are likely to influence the observed pharmacokinetic differences between statins [17].


Pleiotropic effects of pitavastatin.

Davignon J - Br J Clin Pharmacol (2012)

Molecular structures of (A) HMG-CoA and (B) hydrophilic and (C) lipophilic currently available statins. Adapted from Shitara et al. [126]
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376429&req=5

fig01: Molecular structures of (A) HMG-CoA and (B) hydrophilic and (C) lipophilic currently available statins. Adapted from Shitara et al. [126]
Mentions: Statins may be broadly divided into two categories, according to their solubility (Figure 1). Pravastatin and rosuvastatin possess polar side groups attached to hydrophobic ring structures, rendering them hydrophilic, while pitavastatin, atorvastatin, fluvastatin, lovastatin and simvastatin do not, and are consequently classed as lipophilic [2]. Furthermore, the differing chemical structures of individual statins substantially alter the way these molecules are taken up by the liver and catabolized or excreted. Lovastatin and simvastatin, for example, circulate as an inactive, lactone prodrug [13], while atorvastatin and rosuvastatin are biologically active as calcium salts [14, 15]. Rates of biliary excretion, involving a number of transporters, such as breast cancer resistance protein and multidrug resistance-associated protein 2 [16], and hepatic uptake by various transporting polypeptides, are likely to influence the observed pharmacokinetic differences between statins [17].

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montréal (IRCM) and University of Montréal, QC, Canada. Jean.Davignon@ircm.qc.ca

Show MeSH
Related in: MedlinePlus