Hypolipidemic drug from the group of statins. Selective competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutarylcoenzyme A to mevalonic acid, a precursor of sterols, including cholesterol. Triglycerides and cholesterol in the liver are included in VLDL, enter the blood plasma and are transported to peripheral tissues. LDL is formed from VLDL during interaction with LDL receptors.Atorvastatin reduces plasma concentrations of cholesterol and lipoproteins by inhibiting HMG-CoA reductase, synthesizing cholesterol in the liver and increasing the number of LDL receptors in the liver on the cell surface, which leads to increased uptake and catabolism of LDL.Reduces the formation of LDL, causes a pronounced and persistent increase in the activity of LDL receptors. Reduces LDL in patients with homozygous familial hypercholesterolemia, which usually does not respond to therapy with lipid-lowering drugs.It reduces the concentration of total cholesterol by 30-46%, LDL - by 41-61%, apolipoprotein B - by 34-50% and triglycerides - by 14-33%; causes an increase in the concentration of HDL cholesterol and apolipoprotein A. Dose-dependently reduces the LDL content in patients with homozygous hereditary hypercholesterolemia, resistant to therapy with other lipid-lowering drugs.
Absorption is high. Cmax in blood plasma is achieved after 1-2 hours. Food slightly reduces the speed and duration of absorption of the drug (by 25% and 9%, respectively), but the decrease in LDL cholesterol is similar to that with fasting atorvastatin. The concentration of Atorvastatin when applied in the evening is lower than in the morning (approximately 30%). A linear relationship between the degree of absorption and the dose of the drug was revealed. Bioavailability - 12%, systemic bioavailability of inhibitory activity against HMG-CoA reductase - 30%. Low systemic bioavailability due to presystemic metabolism in the gastrointestinal mucosa and during the "first passage" through the liver.
DistributionThe average Vd - 381 liters. Binding to plasma proteins - 98%.
It is metabolized mainly in the liver under the action of cytochrome CYP3A4, CYP3A5 and CYP3A7 with the formation of pharmacologically active metabolites (ortho- and para-hydroxylated derivatives, beta-oxidation products). In vitro, ortho- and para-hydroxylated metabolites have an inhibitory effect on HMG-CoA reductase, comparable to that of atorvastatin. The inhibitory effect of the drug against HMG-CoA reductase is approximately 70% determined by the activity of circulating metabolites.
It is excreted with bile after hepatic and / or extrahepatic metabolism (does not undergo pronounced enterohepatic recirculation). T1 / 2 - 14 hours. The inhibitory activity against HMG-CoA reductase persists for about 20-30 hours due to the presence of active metabolites. Less than 2% of an oral dose is determined in the urine. It is not excreted during hemodialysis. Pharmacokinetics in special patient groups Cmax in women is higher by 20%, AUC - lower by 10%. Cmax in patients with alcoholic cirrhosis is 16 times higher, AUC - 11 times higher than normal.
Indications for Atorvastatin
Atorvastatin is used:
in combination with a diet to reduce elevated levels of total cholesterol, cholesterol / LDL, apolipoprotein B and triglycerides and increase the concentration of HDL cholesterol in patients with primary hypercholesterolemia, heterozygous familial and non-familial hypercholesterolemia and type II mixed (mixed) hyperlipidemia;
in combination with a diet for the treatment of patients with high serum triglycerides (type IV according to Fredrickson) and patients with dysbetalipoproteinemia (type III according to Fredrickson), in whom diet therapy does not give an adequate effect;
to reduce the concentration of total cholesterol and cholesterol / LDL in patients with homozygous familial hypercholesterolemia, when diet therapy and other non-pharmacological treatments are not effective enough.
From the side of the nervous system: more often 2% - insomnia, dizziness; less often 2% - headache, asthenia, malaise, drowsiness, nightmares, paresthesias, peripheral neuropathy, amnesia, emotional lability, ataxia, facial paralysis, hyperkinesia, migraine, depression, hypesthesia, loss of consciousness.
From the sensory organs: less than 2% - amblyopia, tinnitus, dry conjunctiva, disturbed accommodation, hemorrhage in the retina, deafness, glaucoma, parosmia, loss of taste, perversion of taste.
From the cardiovascular system: more often 2% - chest pain; less often 2% - palpitations, vasodilation symptoms, orthostatic hypotension, increased blood pressure, phlebitis, arrhythmia, angina pectoris.
From the hemopoietic system: less than 2% - anemia, lymphadenopathy, thrombocytopenia.
From the respiratory system: more often 2% - bronchitis, rhinitis; less often 2% - pneumonia, dyspnea, exacerbation of bronchial asthma, nosebleeds.
From the digestive system: more often 2% - nausea; less than 2% - heartburn, constipation or diarrhea, flatulence, gastralgia, abdominal pain, decreased or increased appetite, dry mouth, belching, dysphagia, vomiting, stomatitis, esophagitis, glossitis, erosive and ulcerative lesions of the oral mucosa, gastroenteritis, hepatitis, biliary colic, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, impaired liver function, rectal bleeding, melena, bleeding gums, tenesmus.
From the musculoskeletal system: often 2% - arthritis; less often 2% - leg muscle cramps, bursitis, tendosynovitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, torticollis, muscle hypertonicity, joint contractures.
From the urinary system: often 2% - peripheral edema; less often 2% - dysuria (including pollakiuria, nocturia, urinary incontinence or urinary retention, imperative urination, nephritis, hematuria, nephrourolithiasis.
From the genitals and mammary gland: more often 2% - urogenital infections; less often 2% - vaginal bleeding, metrorrhagia, epididymitis, decreased libido, impotence, impaired ejaculation, gynecomastia, mastodynia.
On the part of the skin and subcutaneous tissues: more often 2% - alopecia, xeroderma, increased sweating, eczema, seborrhea, ecchymosis, petechiae.
Allergic reactions: less than 2% - itching, skin rash, contact dermatitis "rarely - urticaria, angioedema, facial edema, photosensitivity, anaphylaxis, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (syndrome Lyella).
On the part of laboratory indicators: less than 2% - hyperglycemia, hypoglycemia, increased serum CPK, albuminuria.
Other: less than 2% - an increase in body weight, exacerbation of gout.
With caution, the drug should be prescribed for alcohol abuse, a history of liver diseases, severe electrolyte imbalance, endocrine and metabolic disorders, arterial hypotension, severe acute infections (sepsis), uncontrolled epilepsy, extensive surgical interventions, injuries, and skeletal muscle diseases.