Tìm theo
Felodipine
Các tên gọi khác (6 ) :
  • (+-)-Ethyl methyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate
  • 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate
  • 4-(2,3-Dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid ethyl methyl ester
  • Felodipina
  • Felodipine
  • Felodipinum
Thuốc tim mạch
Thuốc Gốc
Small Molecule
CAS: 72509-76-3
ATC: C08CA02
ĐG : A-S Medication Solutions LLC , http://orders.a-smeds.com
CTHH: C18H19Cl2NO4
PTK: 384.254
Felodipine is a long-acting 1,4-dihydropyridine calcium channel blocker (CCB)b. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, felodipine prevents calcium-dependent myocyte contraction and vasoconstriction. Felodipine is the most potent CCB in use and is unique in that it exhibits fluorescent activity. In addition to binding to L-type calcium channels, felodipine binds to a number of calcium-binding proteins, exhibits competitive antagonism of the mineralcorticoid receptor, inhibits the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase, and blocks calcium influx through voltage-gated T-type calcium channels. Felodipine is used to treat mild to moderate essential hypertension.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C18H19Cl2NO4
Phân tử khối
384.254
Monoisotopic mass
383.069113515
InChI
InChI=1S/C18H19Cl2NO4/c1-5-25-18(23)14-10(3)21-9(2)13(17(22)24-4)15(14)11-7-6-8-12(19)16(11)20/h6-8,15,21H,5H2,1-4H3
InChI Key
InChIKey=RZTAMFZIAATZDJ-UHFFFAOYSA-N
IUPAC Name
3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
Traditional IUPAC Name
felodipine
SMILES
CCOC(=O)C1=C(C)NC(C)=C(C1C1=C(Cl)C(Cl)=CC=C1)C(=O)OC
Độ tan chảy
145 °C
Độ hòa tan
19.7 mg/L
logP
3.86
logS
-4.7
pKa (Strongest Basic)
5.39
PSA
64.63 Å2
Refractivity
99.2 m3·mol-1
Polarizability
38.04 Å3
Rotatable Bond Count
6
H Bond Acceptor Count
3
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
2
Bioavailability
1
Rule of Five
true
Ghose Filter
true
caco2 Permeability
-4.64
Dược Lực Học : Felodipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. It was widely accepted that CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction; however, some studies have shown that felodipine also binds to and inhibits T-type calcium channels. T-type calcium channels are most commonly found on neurons, cells with pacemaker activity and on osteocytes. The pharmacologic significance of T-type calcium channel blockade is unknown. Felodipine also binds to calmodulin and inhibits calmodulin-dependent calcium release from the sarcoplasmic reticulum. The effect of this interaction appears to be minor. Another study demonstrated that felodipine attenuates the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) by binding to the PDE-1B1 and PDE-1A2 enzyme subunits. CaMPDE is one of the key enzymes involved in cyclic nucleotides and calcium second messenger systems. Felodipine also acts as an antagonist to the mineralcorticoid receptor by competing with aldosterone for binding and blocking aldosterone-induced coactivator recruitment of the mineralcorticoid receptor. Felodipine is able to bind to skeletal and cardiac muscle isoforms of troponin C, one of the key regulatory proteins in muscle contraction. Though felodipine exhibits binding to many endogenous molecules, its vasodilatory effects are still thought to be brought about primarily through inhibition of voltage-gated L-type calcium channels. Similar to other DHP CCBs, felodipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives felodipine additional arterial selectivity. At therapeutic sub-toxic concentrations, felodipine has little effect on cardiac myocytes and conduction cells.
Cơ Chế Tác Dụng : Felodipine is a long-acting 1,4-dihydropyridine calcium channel blocker (CCB)b. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, felodipine prevents calcium-dependent myocyte contraction and vasoconstriction. Felodipine is the most potent CCB in use and is unique in that it exhibits fluorescent activity. In addition to binding to L-type calcium channels, felodipine binds to a number of calcium-binding proteins, exhibits competitive antagonism of the mineralcorticoid receptor, inhibits the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase, and blocks calcium influx through voltage-gated T-type calcium channels. Felodipine is used to treat mild to moderate essential hypertension. Felodipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through voltage-gated L-type calcium channels. It reversibly competes against nitrendipine and other DHP CCBs for DHP binding sites in vascular smooth muscle and cultured rabbit atrial cells. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of felodipine result in an overall decrease in blood pressure. Felodipine may be used to treat mild to moderate essential hypertension.
Dược Động Học :
▧ Absorption :
Is completely absorbed from the gastrointestinal tract; however, extensive first-pass metabolism through the portal circulation results in a low systemic availability of 15%. Bioavailability is unaffected by food.
▧ Volume of Distribution :
* 10 L/kg
▧ Protein binding :
99%, primarily to the albumin fraction.
▧ Metabolism :
Hepatic metabolism primarily via cytochrome P450 3A4. Six metabolites with no appreciable vasodilatory effects have been identified.
▧ Route of Elimination :
Although higher concentrations of the metabolites are present in the plasma due to decreased urinary excretion, these are inactive. Animal studies have demonstrated that felodipine crosses the blood-brain barrier and the placenta.
▧ Half Life :
17.5-31.5 hours in hypertensive patients; 19.1-35.9 hours in elderly hypertensive patients; 8.5-19.7 in healthy volunteers.
▧ Clearance :
* 0.8 L/min [Young healthy subjects]
Độc Tính : Symptoms of overdose include excessive peripheral vasodilation with marked hypotension and possibly bradycardia. Oral rat LD50 is 1050 mg/kg.
Chỉ Định : For the treatment of mild to moderate essential hypertension.
Tương Tác Thuốc :
  • Amobarbital The barbiturate, amobarbital, decreases the effect of felodipine.
  • Aprobarbital The barbiturate, aprobarbital, decreases the effect of felodipine.
  • Butabarbital The barbiturate, butabarbital, decreases the effect of felodipine.
  • Butalbital The barbiturate, butalbital, decreases the effect of felodipine.
  • Butethal The barbiturate, butethal, decreases the effect of felodipine.
  • Carbamazepine Carbamazepine may increase the metabolism of felodipine. Monitor for changes in the therapeutic and adverse effects of felodipine if carbamazepine is initiated, discontinued or dose changed.
  • Dihydroquinidine barbiturate The barbiturate, dihydroquinidine barbiturate, decreases the effect of felodipine.
  • Erythromycin Erythromycin increases the effect of felodipine
  • Ethotoin The hydantoin decreases the effect of felodipine
  • Fosphenytoin The hydantoin decreases the effect of felodipine
  • Heptabarbital The barbiturate, heptabarbital, decreases the effect of felodipine.
  • Hexobarbital The barbiturate, hexobarbital, decreases the effect of felodipine.
  • Itraconazole Itraconazole may increase the therapeutic and adverse effects of felodipine.
  • Josamycin Erythromycin increases the effect of felodipine
  • Mephenytoin The hydantoin decreases the effect of felodipine
  • Methohexital The barbiturate, methohexital, decreases the effect of felodipine.
  • Methylphenobarbital The barbiturate, methylphenobarbital, decreases the effect of felodipine.
  • Nelfinavir Nelfinavir increases the effect and toxicity of felodipine
  • Oxcarbazepine Oxcarbazepine decreases the levels of felodipine
  • Pentobarbital The barbiturate, pentobarbital, decreases the effect of felodipine.
  • Phenobarbital The barbiturate, phenobarbital, decreases the effect of felodipine.
  • Phenytoin The hydantoin decreases the effect of felodipine
  • Primidone The barbiturate, primidone, decreases the effect of felodipine.
  • Quinidine barbiturate The barbiturate, quinidine barbiturate, decreases the effect of felodipine.
  • Quinupristin This combination presents an increased risk of toxicity
  • Secobarbital The barbiturate, secobarbital, decreases the effect of felodipine.
  • Tacrolimus Felodipine increases tacrolimus levels
  • Talbutal The barbiturate, talbutal, decreases the effect of felodipine.
  • Telithromycin Telithromycin may reduce clearance of Felodipine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Felodipine if Telithromycin is initiated, discontinued or dose changed.
  • Thiopental The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Felodipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Felodipine if Thiopental is initiated, discontinued or dose changed.
  • Tipranavir Tipranavir, co-administered with Ritonavir, may alter the concentration of Felopidine. Monitor for efficacy and adverse/toxic effects of Felopidine.
  • Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
  • Tretinoin The moderate CYP2C8 inhibitor, Felopidine, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Felopidine is initiated, discontinued to dose changed.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of felodipine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of felodipine if voriconazole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Tablet, extended release - Oral - 10 mg
Tablet, extended release - Oral - 2.5 mg
Tablet, extended release - Oral - 5 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Felodur ER
  • Công ty :
    Sản phẩm biệt dược : Felogard
  • Công ty :
    Sản phẩm biệt dược : Penedil
  • Công ty : AstraZeneca
    Sản phẩm biệt dược : Plendil
  • Công ty : AstraZeneca
    Sản phẩm biệt dược : Plendil Depottab
  • Công ty : AstraZeneca
    Sản phẩm biệt dược : Plendil ER
  • Công ty : AstraZeneca
    Sản phẩm biệt dược : Plendil Retard
  • Công ty : Sanofi-Aventis
    Sản phẩm biệt dược : Renedil
  • Công ty :
    Sản phẩm biệt dược : Splendil
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01023
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=3333
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506968
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00319
ChemSpider
http://www.chemspider.com/Chemical-Structure.3216.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50017710
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0378-5011-01
PharmGKB
http://www.pharmgkb.org/drug/PA449591
Wikipedia
http://en.wikipedia.org/wiki/Felodipine
RxList
http://www.rxlist.com/cgi/generic2/felo.htm
PDRhealth
http://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=ple1339.html&contentName=Plendil&contentId=593
Drugs.com
http://www.drugs.com/cdi/felodipine.html
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