Tìm theo
Pravastatin
Các tên gọi khác (5 ) :
  • (+)-(3R,5R)-3,5-Dihydroxy-7-[(1S,2S,6S,8S,8ar)-6-hydroxy-2-methyl-8-{[(S)-2-methylbutyryl]oxy}-1,2,6,7,8,8a-hexahydro-1-naphthyl]heptanoic acid
  • Pravastatin acid
  • Pravastatina
  • Pravastatine
  • Pravastatinum
Thuốc tim mạch
Thuốc Gốc
Small Molecule
CAS: 81093-37-0
ATC: C10AA03
ĐG : Advanced Pharmaceutical Services Inc.
CTHH: C23H36O7
PTK: 424.5277
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.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
Phân tử khối
424.5277
Monoisotopic mass
424.246103506
InChI
InChI=1S/C23H36O7/c1-4-13(2)23(29)30-20-11-17(25)9-15-6-5-14(3)19(22(15)20)8-7-16(24)10-18(26)12-21(27)28/h5-6,9,13-14,16-20,22,24-26H,4,7-8,10-12H2,1-3H3,(H,27,28)/t13-,14-,16+,17+,18+,19-,20-,22-/m0/s1
InChI Key
InChIKey=TUZYXOIXSAXUGO-PZAWKZKUSA-N
IUPAC Name
(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
Traditional IUPAC Name
pravastatin
Độ tan chảy
171.2 - 173°C
Độ hòa tan
Soluble
logP
0.59
logS
-3.2
pKa (strongest acidic)
4.21
pKa (Strongest Basic)
-2.7
PSA
124.29 Å2
Refractivity
113.6 m3·mol-1
Polarizability
46.56 Å3
Rotatable Bond Count
11
H Bond Acceptor Count
6
H Bond Donor Count
4
Physiological Charge
-1
Number of Rings
2
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : 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.
Cơ Chế Tác Dụng : 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. 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. Pravastatin sodium produces its lipid-lowering effect in two ways. First, as a consequence of its reversible inhibition of HMG-CoA reductase activity, it effects modest reductions in intracellular pools of cholesterol. This results in an increase in the number of LDL-receptors on cell surfaces and enhanced receptor-mediated catabolism and clearance of circulating LDL. Second, pravastatin inhibits LDL production by inhibiting hepatic synthesis of VLDL, the LDL precursor.
Dược Động Học :
▧ Absorption :
Pravastatin is rapidly absorbed with peak plasma levels of the parent compound achieved 1 to 1.5 hours after administration. The average oral absorption of pravastatin is 34% and absolute bioavailability is 17%. These values however, are variable. Food decreases the systemic bioavailability but the lipid-lowering effect is not impacted. When 20 mg of pravastatin is given orally, the pharmacokinetic parameters are as follows: Cmax = 23.3-26.3 ng/mL; AUC = 54.7 to 62.2 ng•hr/mL.
▧ Protein binding :
50% bound to human plasma proteins.
▧ 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. Furthermore, the major degradation product is the 3α-hydroxy isomeric metabolite, which has one-tenth to one-fortieth the HMG-CoA reductase inhibitory activity of the parent compound.
▧ Route of Elimination :
Approximately 20% of a radiolabeled oral dose is excreted in urine and 70% in the feces. After intravenous administration, 47% of total body clearance was via renal excretion, while 53% was eliminated by non-renal routes.
▧ Half Life :
77 hours
Độc Tính : Side effects include diarrhea, nausea, constipation, gas abdominal pain, myopathy, myositis, rhabdomyolysis, and hepatotoxicity. LD50= 12,000 mg/kg (orally in rat)
Chỉ Định : For the treatment of hypercholesterolemia and to reduce the risk of cardiovascular disease.
Tương Tác Thuốc :
  • 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.
Liều Lượng & Cách Dùng : Tablet - Oral - 10 mg, 20 mg, 40 mg, 80 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
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