Abstract
Six statins are currently available in the Czech Republic. The most commonly used are atorvastatin, simvastatin and rosuvastatin and their share of total consumption is around 95 %.
The main difference among the statins lies in their pharmacokinetic properties. These affect the variability of their plasma level, which is largely reflected in their tolerability and duration of action, which in turn determines their efficacy.
Lipophilic statins (atorvastatin, lovastatin and simvastatin) are substrates of the elimination transporters P-glycoprotein (P-gp) and CYP3A4/5 and inhibition or induction of these two systems will significantly affect statin level and tolerability. Fluvastatin is a substrate of the CYP2C9 isoenzyme and this oxidase is significantly less sensitive to any influences of its activity.
Hydrophilic statins (rosuvastatin, pitavastatin and pravastatin) are transformed by CYP isoenzymes and their bioavailability is not significantly affected by P-gp. Variability of the levels of this group of statins is significantly smaller.
Access of all statins to their site of action - the hepatocyte - is influenced by the polymorphic OATP1B1influx pump, a transporter with significant variability of efficacy. Sufficient influx of statins into the hepatocyte is a pre-condition of their pharmacodynamic effect, i.e. the inhibition of HMG-CoA reductase as well as their elimination into bile.
Low OATP1B1 activity may lead to insufficient efficacy and may in contrast induce adverse effects. In the case of simvastatin, which has a strong affinity to this pump, the incidence of myopathy and myalgia is significantly affected by transporter activity.
Zero activity increases simvastatin toxicity (especially the incidence of myalgia/myopathy) 20-30 times. Statins are competitive inhibitors of HMG-CoA reductase.
Adequate statin concentration during the dosing period determines, together with the statin dose, the resulting lipid-lowering effect. In the case of longer-acting statins (atorvastatin and rosuvastatin), the inhibition of HMG-CoA reductase is more stable and reduction of LDL cholesterol greater.
In pharmacotherapy, these properties are reflected in the degree of inhibition of cholesterol synthesis. The effect on LDL cholesterol reduction is thus greatest in the case of long-acting statins (rosuvastatin and atorvastatin).
On the other hand, variability in simvastatin exposure is reflected in a higher incidence of adverse effects, especially myalgia. Conversely, fluvastatin whose bioavailability is relatively stable and in whose case influx into the hepatocyte is only minimally dependent on the OATP1B1 transporter is relatively better tolerated.
Unfortunately, short-term effect implies a lower hypolipidemic effect, with acceleration of cholesterol synthesis at the time of reduced statin concentrations