Latin name of the substance is Rosuvastatin
Pharmacological group substances Rosuvastatin
Nosological classification (ICD-10)
Characteristics of the substance Rosuvastatin
Lipid-lowering DV is an inhibitor of HMG-CoA reductase.
Rosuvastatin – hypolipidemic DV – is a selective, competitive inhibitor of HMG-CoA reductase – an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonic acid – a precursor of cholesterol. The main target of rosuvastatin is the liver, where Xc synthesis and LDL catabolism occur. Increases the number of hepatic LDL receptors on the cell surface, increasing the uptake and catabolism of LDL, which in turn leads to inhibition of the synthesis of VLDL, thereby reducing the total amount of LDL and VLDL.
Rosuvastatin reduces elevated plasma concentrations of Xc-LDL, total Xc, triglycerides (TG), increases the concentration of Xc-HDL. It also reduces the concentration of apolipoprotein B (ApoB), Xc-non-LPVP, XC-VLDL, TG-VLDL and increases the concentration of apolipoprotein A-1 (ApoA-1) in plasma. Rosuvastatin reduces the ratio of Xc-LDL / Xc-HDL, total Xc / Xc-HDL and Xc-non-LPVP / Xc-HDL and the ratio ApoV / ApoA-1.
The therapeutic effect develops during the 1st week after the start of therapy, after 2 weeks of treatment reaches 90% of the maximum possible effect. The maximum therapeutic effect is usually achieved by the 4th week of therapy and is maintained with further regular use of this drug.
Rosuvastatin is effective in adult patients with hypercholesterolemia with or without concomitant hypertriglyceridemia, regardless of race, gender, or age.
In 80% of patients with hypercholesterolemia IIa and IIb type according to Fredrikson (the average initial concentration of Xc-LDL is about 4.8 mmol / l), while receiving rosuvastatin in a dose of 10 mg, the concentration of Xc-LDL reaches less than 3 mmol / l. In patients with homozygous familial hypercholesterolemia who received rosuvastatin in doses of 20–40 mg, the average decrease was 22%.
The additive effect is observed in combination with fenofibrate in relation to the content of TG and with nicotinic acid in lipid-lowering doses in relation to the concentration of HD-C HDL.
Absorption and distribution
Cmax of rosuvastatin in plasma is reached approximately 5 hours after ingestion. Absolute bioavailability is approximately 20%.
Metabolized predominantly by the liver, which is the main organ that synthesizes Xc and metabolizes Xc-LDL. Vd rosuvastatin is approximately 134 liters. Approximately 90% of rosuvastatin binds to plasma proteins, mainly albumin.
Subject to limited metabolism (about 10%). Rosuvastatin is a non-specific substrate of cytochrome P450. The main isoenzyme involved in rosuvastatin metabolism is the isoenzyme CYP2C9. CYP2C19, CYP3A4, CYP2D6 isoenzymes are less involved in metabolism. The main metabolites identified are N-desmethylrosuvastatin and lactone metabolites.
N-desmethylrosuvastatin is approximately 50% less active than rosuvastatin, lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity on inhibition of plasma HMG-CoA reductase is provided by rosuvastatin, the rest is provided by its metabolites.
About 90% of the dose of rosuvastatin is excreted unchanged through the intestines (including absorbed and unabsorbed rosuvastatin). The rest is excreted by the kidneys. T1 / 2 of blood plasma is approximately 19 hours (does not change with an increase in the dose of rosuvastatin). The geometric mean plasma clearance is 50 l / h (the coefficient of variation is 21.7%). As in the case of other HMG-CoA reductase inhibitors, membrane transplantation Xc is involved in the hepatic uptake of rosuvastatin, which plays an important role in the hepatic elimination of rosuvastatin.
The systemic exposure of rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily intake.
Special patient groups
Age and gender. Gender and age do not have a clinically significant effect on rosuvastatin pharmacokinetics.
Ethnic groups. Pharmacokinetic studies have shown approximately a twofold increase in the median AUC and Cmax in plasma blood of rosuvastatin in patients of the Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with European patients; Indians showed an increase in the median AUC and Cmax by 1.3 times. Pharmacokinetic analysis revealed no clinically significant differences in pharmacokinetics among patients of the Caucasian and Negroid races.
Renal failure. In patients with mild to moderate renal insufficiency, the plasma concentration of rosuvastatin or N-desmethylrozuvastatin does not change significantly. In patients with severe renal insufficiency (Cl creatinine 60 ml / min); age over 65; history of liver disease; sepsis; hypotension; extensive surgical interventions; injuries; severe metabolic, endocrine or electrolyte disturbances, or uncontrolled seizures; simultaneous use with ezetimibe.
Use during pregnancy and lactation
Rosuvastatin is contraindicated during pregnancy and lactation.
Women of reproductive age should use adequate methods of contraception.
Since Xc and substances synthesized from Xc are important for fetal development, the potential risk of inhibiting HMG-CoA reductase for the fetus outweighs the benefits of rosuvastatin during pregnancy.
In the event of pregnancy in the course of therapy, the use of the agent should be immediately terminated.
There is no data on the release of rosuvastatin with breast milk (it is known that other HMG-CoA reductase inhibitors are able to stand out with breast milk), therefore, during the period of breastfeeding, the use of the agent must be stopped.
Category of action on the fetus by the FDA – X.
Side Effects of Rosuvastatin
The side effects observed with the use of rosuvastatin are usually slightly pronounced and disappear on their own. As with the use of other inhibitors of HMG-CoA reductase, the frequency of side effects is mainly dose-dependent.
Classification of the incidence of side effects WHO: very often (≥1 / 10); often (≥1 / 100, ®