What Is Rosuvastatin?

Rosuvastatin is a selective HMG-CoA reductase inhibitor. HMG-CoA reductase inhibitors are rate-limiting enzymes that convert 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol. Rosuvastatin's main site of action is the liver, a targeted organ that lowers cholesterol. Rosuvastatin increases the number of liver LDL cell surface receptors, promotes the absorption and catabolism of LDL, and inhibits VLDL liver synthesis, thereby reducing the total number of VLDL and LDL particles.

Rosuvastatin is a selective HMG-CoA reductase inhibitor. HMG-CoA reductase inhibitors are rate-limiting enzymes that convert 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol. Rosuvastatin's main site of action is the liver, a targeted organ that lowers cholesterol. Rosuvastatin increases the number of liver LDL cell surface receptors, promotes the absorption and catabolism of LDL, and inhibits the liver synthesis of VLDL, thereby reducing the total number of VLDL and LDL particles.

Chinese name

Rosuvastatin

Foreign name

rosuvastatin

Product name

Crestor

Formulation specifications

Tablets, each 10mg / 20mg / 40mg.

Use

oral

Amount

Dosage ranges from 10 to 40 mg

Rosuvastatin compounds

Rosuvastatin, trade name Cotin, is a statin that is used in combination with exercise, diet control, and weight loss to treat hypercholesterolemia and other related symptoms. It is also used to prevent cardiovascular disease. Rosuvastatin was developed by Yoshino Pharmaceutical. Can be determined to be the fourth largest drug sales in the United States, and in 2013 generated a profit of about 520 million US dollars.

Rosuvastatin Basic Information

Chinese name: Ruishuvastatin

Chinese alias: Rovastatin; Russellstatin; Rosuvastatin; 7- [4- (4-fluorophenyl) -6-isopropyl-2- (methyl-methanesulfonyl-amino) -pyrimidine-5 -Yl] -3,5-dihydroxyheptan-6-enoic acid;

English name: Rosuvastatin

English alias: (3R, 5S, 6E) -7- [4- (4-fluorophenyl) -2- (N-methylmethanesulfonamido) -6- (propan-2-yl) pyrimidin-5-yl] -3,5- dihydroxyhept-6-enoic acid; 7- [4- (4-Fluorophenyl) -6- (1-methylethyl) -2- (methyl-methylsulfonyl-amino) -pyrimidin-5-yl] -3,5-dihydroxy-hept -6-enoic acid; ZD 4522; X-Plended; Crestor;

CAS number: 287714-41-4

Molecular formula: C ₂₂ H ₂₄ D ₃ FN ₃ NaO ₆ S

Molecular weight: 506.53800

Exact mass: 506.16900

PSA: 152.13000

LogP: 2.14780

Rosuvastatin physical and chemical properties

Density: 1.368 g / cm ³

Boiling point: 745.6ºC at 760 mmHg

Flash point: 404.7ºC

Refractive index: 1.597

Vapor pressure: 2.38E-23mmHg at 25 ° C ^[1]

Rosuvastatin Structural Features

Although lovastatin has a dihydroxyheptanoic acid moiety that is common to statins, the rest of its molecular structure is very different from other similar drugs.The presence of polar mesylamino groups makes it less lipophilic. . This means that its passive diffusion ability is low and it is difficult to enter non-hepatocytes. However, it can be taken up by liver cells in large quantities through a selective organic anion transport process, and has the characteristics of selectively distributing and acting on HMG-CoA reductase in the liver. At the same time, the relatively water-soluble nature of its structure also makes it possible to avoid the deficiency of extensive metabolism of cytochrome P450 before elimination, and greatly reduce the probability of interaction with other drugs.

Rovastatin structure

The picture on the right shows the structure of lovastatin

Rosuvastatin Related Drug Sheet Information

Rosuvastatin classification name

Primary classification: Circulatory system secondary classification: Adjusting blood lipids and anti-atherosclerotic drugs Third classification: HMG CoA reductase inhibitor

Rosuvastatin drug English name

Rosuvastatin

Rosuvastatin drug alias

Rosuvastatin, Cotin, Crestor

Rosuvastatin drug dosage form

Rosuvastatin coated tablets: 5 mg / tablet; 10 mg / tablet; 20 mg / tablet; 40 mg / tablet. Store at 20 25 in a sealed and moisture-proof place.

Rosuvastatin pharmacological effects

Hypolipidemic effect

Rovastatin has a significant effect on lowering blood lipids. Generally, statins lower the level of low-density lipoprotein cholesterol (LDL-C) by 17% to 54%. The results of the phase II clinical trial of lovastatin showed that at a dose of 80 mg, it reduced LDL-C by 65%, which is currently the most effective statin. Rovastatin can increase the number of LDL receptors. In human hepatocellular carcinoma, lovastatin increases LDL receptor mRNA by about 10 times more than pravastatin.

2. Selective effect on liver cells

Hepatocyte-derived cholesterol is the main cause of blood cholesterol, while non-hepatocyte-derived cholesterol is necessary for normal cells. Rovastatin's main site of action is the liver. From the perspective of inhibiting sterol synthesis, the drug is more selective for rat liver than for peripheral tissues, and it is more selective for liver tissue than pravastatin or simvastatin. Sex is high. Through active absorption process, lovastatin is absorbed into hepatocytes, and its inhibitory effect on cholesterol in rat liver cells is 1000 times higher than that in fibroblasts.

3. Anti-atherosclerotic effect

Rovastatin can lower blood lipids, reduce lipid infiltration and foam cell formation, and is beneficial for delaying atherosclerosis; the drug can also block hydroxymethylglutaric acid pathways, especially inhibit the isoprenoid metabolites. Formation and inhibition of smooth muscle cell proliferation and promotion of apoptosis stabilize the atherosclerotic plaque and delay the occurrence and development of atherosclerosis.

Rosuvastatin Pharmacokinetics

Rovastatin is one of two statins with the strongest hydrophilicity.In addition to the dihydroxyheptanoic acid moiety which is an effective group shared by statins, it also has a polar mesylamino group, showing Low lipophilicity. Rovastatin's hydrophilicity means that its passive diffusion ability is low and it is difficult to enter non-hepatocytes, but it can be taken up by liver cells in large quantities through a selective organic anion transport process. Three randomized, placebo-controlled, double-blind trials of healthy male volunteers using lovastatin 20 to 80 mg showed dose and plasma maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC0 ~ 24) All have a linear relationship. Rovastatin was administered at 40 mg · d-1, and after 7 days, it was found that Cmax at steady state was 37.0 g · L-1, tmax was 3h, t1 / 2 was 20.8 h, and AUC0 24 was 256 g · h · L -1. Small-scale non-blind trials have shown that the pharmacokinetics of the drug are not affected by age, sex, and duration of administration. In a non-blind, randomized, crossover trial, 21 healthy volunteers used Rovastatin 10 mg at 7:00 or 18:00 for a total of 14 days, and no statistical significance was observed with the time of medication. The difference between Cmax and AUC0 24. Of the 6 healthy male volunteers, 90% of radiolabeled lovastatin 20 mg appeared in the stool, and 10% was excreted with urine. In stool, 92% were prototype compounds and 8% were metabolites, suggesting that the drug was mainly excreted as a prototype. Rovastatin is mainly metabolized by CYP2C9 and CYP2C19 and not by CYP3A4 isoenzymes, which means that the interaction with other lipid-lowering drugs metabolized by CYP3A4 isoenzymes is reduced, thereby reducing the possibility of adverse reactions. ^[2]

Rosuvastatin Clinical Application

It is clinically used for the treatment of primary hypercholesterolemia, familial hypercholesterolemia and other causes of lipid disorders.

The summary, structural characteristics, clinical application, and pharmacological effects of lovastatin were edited and edited by Ding Hong of Chemicalbook.

Rosuvastatin adverse reactions

The safety and tolerability of this product is the best among statins. The incidence of adverse reactions in 647 patients treated with lovastatin was similar to that of placebo (55%: 53%). The common adverse reactions of lovastatin in 2579 patients were pharyngitis (12.2%), pain (6.7%), headache (6.6%), influenza-like syndrome (5.3%), and myalgia (5.1%). Similar to pravastatin, atorvastatin, and simvastatin. Increasing the dose of this product does not increase adverse reactions. Clinically, there were no abnormalities in ALT (greater than 3 times the upper limit of normal) or creatine kinase (CPK, greater than 10 times the upper limit of normal).

Rosuvastatin indications

For the treatment of primary hypercholesterolemia and mixed lipid disorders.

Rosuvastatin Contraindications

1. Disable allergic patients. 2. Disabled in patients with active liver disease. 3. Disable myopathy patients. 4. The pregnancy toxicity rating is X, pregnant women are prohibited.

Rosuvastatin precautions

1. Excessive drinkers should be used with caution. 2. Use with caution in patients with a history of liver disease. 3. The concentration of this product in rat milk is 3 times of the plasma drug concentration. Use with caution in lactating women. 4. Take a low cholesterol diet before and during the medication. The dosage varies depending on the target of the treatment. 5. Perform liver function tests before using this product and within 3 months of treatment. If serum transaminase is 3 times higher than normal, this product should be discontinued or reduced. 6. If there is unknown myalgia, muscle weakness or suspected myopathy, this product should be discontinued immediately. 7. There are no differences in pharmacokinetics among different genders and age groups. There are no data on the safety of medication for children under 8.8 years of age. 9. Mild to moderate renal insufficiency has no effect on the plasma concentration of this product. The plasma concentration of severe renal insufficiency is 3 times that of normal patients, and that of severe liver dysfunction can reach 2 times that of normal patients. 10. Supportive treatment is used for drug overdose, which is not easy to clear through dialysis.

Rosuvastatin dosage

Hypercholesterolemia and mixed dyslipidemia (hyperlipoproteinemia type a and b): Oral, the recommended starting dose is 10mg, the usual dose is 5 to 40mg, once a day, taken before or after meals. Homozygous familial hypercholesterolemia: Orally, the recommended starting dose is 20 mg once daily, and the maximum daily dose is 40 mg. Asian patients: The recommended starting dose is 5mg once daily. The dose can be adjusted to 5mg, 10mg, 20mg daily according to the situation. Patients taking cyclosporine: The recommended dose is 5 mg once daily. Patients with severe renal insufficiency (creatinine clearance <30ml / min): The recommended dose is 5mg once a day, and the maximum daily dose is 10mg.

Rosuvastatin drug interactions

1. This product is not metabolized by P450 3A4. Taking it with ketoconazole has no effect on the plasma drug concentration of this product. 2. Simultaneous use with erythromycin can reduce the AUC and Cmax of this product by 20% and 31%, but it has no clinical significance. 3. Concurrent use with itraconazole increased the AUC (39%, 28%) of this product (10mg, 80mg). 4. Concurrent use of fluconazole increases the AUC of this product by 14%. 5. Simultaneous use with cyclosporine, the plasma drug concentration of cyclosporine has not changed, but the Cmax of this product increased by 11 times, the AUC increased by 7 times, combined use with cyclosporine should be careful, and consider the dose of this product. 6. Combination with warfarin or digoxin has no effect on the plasma drug concentration of warfarin and digoxin. 7. In combination with fenofibrate, there is no change in blood concentration of both. 8. Combined with Gefibet, the AUC and Cmax of this product increase by 90% and 120%, respectively. 9. Combined with antacids (aluminum hydroxide, magnesium hydroxide), there is no change in plasma drug concentration. 10. Combined with oral contraceptives, the blood concentration of ethinyl estradiol is increased by 26%, and the blood concentration of norethindrone is increased by 34%. ^[3]