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药品详细

Pravastatin(普伐他汀)

化学结构式图
中文名
普伐他汀
英文名
Pravastatin
分子式
C23H36O7
化学名
(3R,5R)-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-{[(2S)-2-methylbutanoyl]oxy}-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid
分子量
Average: 424.5277
Monoisotopic: 424.246103506
CAS号
81093-37-0
ATC分类
C10A 未知
药物类型
small molecule
阶段
approved
商品名
Elisor;Lipostat;Mevalotin;Mevinolin;Oliprevin;Pravachol;Pravaselect;Selectin;Selipran;Vasten;
同义名
Pravastatin Sodium;Pravastatina [Spanish];Pravastatine [French];Pravastatinum [Latin];
基本介绍

Pravastatin is a cholesterol-lowering agent that belongs to a class of medications known as statins. It was derived from microbial transformation of mevastatin, the first statin discovered. It is a ring-opened dihydroxyacid with a 6’-hydroxyl group that does not require in vivo activation. Pravastatin is one of the lower potency statins; however, its increased hydrophilicity is thought to confer advantages such as minimal penetration through lipophilic membranes of peripheral cells, increased selectivity for hepatic tissues, and a reduction in side effects compared with lovastatin and simvastatin.

生产厂家
  • Apotex corp
  • Bristol myers squibb
  • Dr reddys laboratories inc
  • Glenmark generics ltd
  • Lek pharmaceuticals dd
  • Lupin pharmaceuticals inc
  • Matrix laboratories ltd
  • Mylan pharmaceuticals inc
  • Pliva hrvatska doo
  • Ranbaxy laboratories ltd
  • Teva pharmaceuticals usa
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Zydus pharmaceuticals usa inc
封装厂家
参考
Synthesis Reference Not Available
General Reference Not Available
剂型
规格
化合物类型
Type small molecule
Classes
  • Statins
Substructures
  • Statins
  • Carboxylic Acids and Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Acetates
  • Ethers
  • Isoprenes
  • Alcohols and Polyols
  • Cyclohexenes and Derivatives
适应症
hyperlipidemi 高血脂;
药理
Indication For the treatment of hypercholesterolemia and to reduce the risk of cardiovascular disease.
Pharmacodynamics The primary cause of cardiovascular (CV) disease is atherosclerotic plaque formation and sustained elevation of cholesterol in the blood increases the risk of CV disease. Pravastatin lowers hepatic production of cholesterol by competitively inhibiting HMG-CoA reductase, the enzyme that catalyzes the rate-limiting step in the cholesterol biosynthesis pathway via the mevalonic acid pathway. Decreased hepatic cholesterol levels causes increased uptake of low density lipoprotein (LDL) cholesterol and reduces cholesterol levels in the circulation. Pravastatin also inhibits hepatic synthesis if VLDL. At therapeutic doses, pravastatin lowers LDL cholesterol by 20-30%, increase high density lipoprotein (HDL) cholesterol by 3-10%, and decrease plasma triglycerides by 19-34%. HDL cholesterol is thought to confer protective effects against CV disease, whereas high LDL and triglyceride levels are associated with higher risk of disease.
Mechanism of action Pravastatin is structurally similar to the HMG, a substituent of the endogenous substrate of HMG-CoA reductase. Unlike its parent compound, mevastatin, and statins such as lovastatin and simvastatin, pravastatin does not need to be activated in vivo. Its hydrolyzed lactone ring mimics the tetrahedral intermediate produced by the reductase allowing the agent to bind with a much greater affinity than its natural substrate. The bicyclic portion of pravastatin binds to the coenzyme A portion of the active site.
Absorption Average oral absorption of pravastatin is 34% and absolute bioavailability is 17%.
Volume of distribution Not Available
Protein binding 50%
Metabolism
Hepatic, there is a small amount of metabolism by P450 enzymes, but this effect is so minimal that inhibitory pharmacokinetic drug interactions have no real effect on its overall activity and elimination. An in vitro study which found moderate affinity for P450 2C9 (major), 2D6 and 3A4.
Route of elimination Approximately 20% of a radiolabeled oral dose is excreted in urine and 70% in the feces.
Half life 77 hours
Clearance Not Available
Toxicity Side effects include diarrhea, nausea, constipation, gas abdominal pain, myopathy, myositis, rhabdomyolysis, and hepatotoxicity. LD50=mg/kg (orally in rat)
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00089 Pravastatin Pathway SMP00089
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 326 °C Not Available
water solubility 2464mg/L Not Available
logP 2.2 Not Available
Predicted Properties
Property Value Source
water solubility 2.42e-01 g/l ALOGPS
logP 2.23 ALOGPS
logP 1.65 ChemAxon
logS -3.2 ALOGPS
pKa (strongest acidic) 4.21 ChemAxon
pKa (strongest basic) -2.7 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 6 ChemAxon
hydrogen donor count 4 ChemAxon
polar surface area 124.29 ChemAxon
rotatable bond count 11 ChemAxon
refractivity 113.6 ChemAxon
polarizability 46.56 ChemAxon
药物相互作用
Drug Interaction
Bezafibrate Increased risk of myopathy/rhabdomyolysis
Boceprevir Boceprevir increases pravastatin AUC by 60% with boceprevir. Concomitant therapy should be closely monitored.
Colchicine Increased risk of rhabdomyolysis with this combination
Colesevelam Bile Acid Sequestrants may decrease the serum concentration of Pravastatin. Administer pravastatin at least 1 hour before or 4 hours after administration of bile-acid resins (eg, cholestyramine, colestipol, colesevelam) to minimize the risk for any significant interaction.
Cyclosporine Possible myopathy and rhabdomyolysis
Fenofibrate Increased risk of myopathy/rhabdomyolysis
Gemfibrozil Increased risk of myopathy/rhabdomyolysis
Repaglinide Substrates of organic anion transporters may increase levels of repaglinide. Monitor concomitant therapy closely.
Tipranavir Tipranavir may increase the plasma concentration of Pravastatin. Consider alternate therapy.
食物相互作用
  • Avoid alcohol.
  • Avoid drastic changes in dietary habit.
  • Take without regard to meals.

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