Tìm theo
Cilazapril
Các tên gọi khác (2) :
  • Cilazapril
  • Cilazaprilum
angiotensin converting enzyme inhibitors, antihypertensive agents
Thuốc Gốc
Small Molecule
CAS: 92077-78-6
ATC: C09AA08
CTHH: C22H31N3O5
PTK: 417.4986
Cilazapril is an ACE inhibtor class drug used in the treatment of hypertension and heart failure. It belongs to the angiotensin-converting enzyme inhibitors (ACE inhibitors) class of drugs. It is a prodrug that is hydrolyzed after absorption to its main metabolite cilazaprilat. It is branded as Inhibace in Canada and other countries, Vascace and Dynorm in a number of European countries, among many other names. None of these varieties are available in the United States.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C22H31N3O5
Phân tử khối
417.4986
Monoisotopic mass
417.226371117
InChI
InChI=1S/C22H31N3O5/c1-2-30-22(29)18(13-12-16-8-4-3-5-9-16)23-17-10-6-14-24-15-7-11-19(21(27)28)25(24)20(17)26/h3-5,8-9,17-19,23H,2,6-7,10-15H2,1H3,(H,27,28)/t17-,18-,19-/m0/s1
InChI Key
InChIKey=HHHKFGXWKKUNCY-FHWLQOOXSA-N
IUPAC Name
(1S,9S)-9-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}-10-oxo-octahydro-1H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid
Traditional IUPAC Name
(1S,9S)-9-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}-10-oxo-octahydropyridazino[1,2-a][1,2]diazepine-1-carboxylic acid
SMILES
CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CCCN2CCC[C@H](N2C1=O)C(O)=O
Độ tan chảy
98 ºC with decomposition
Độ hòa tan
Water (25 ºC) 0.5 g/100 mL
logP
0.8
logS
-2.6
pKa (strongest acidic)
3.41
pKa (Strongest Basic)
5.35
PSA
99.18 Å2
Refractivity
110.56 m3·mol-1
Polarizability
44.73 Å3
Rotatable Bond Count
9
H Bond Acceptor Count
6
H Bond Donor Count
2
Physiological Charge
-1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học : Cilazapril inhibits the production angiotensin II. By doing so, it decreases sodium and water reabsorption (via aldosterone) and it decreases vasoconstriction. The combined effect of this is a decrease in vascular resistance, and therefore, blood pressure. The absolute bioavailability of cilazaprilat after oral administration of cilazapril is 57% based on urinary recovery data. (The absolute bioavailability of cilazaprilat after oral administration of cilazaprilat is 19%.) Ingestion of food immediately before the administration of cilazapril reduces the average peak plasma concentration of cilazaprilat by 29%, delays the peak by one hour and reduces the bioavailability of cilazaprilat by 14%. These pharmacokinetic changes have little influence on plasma ACE inhibition.
Cơ Chế Tác Dụng : Cilazapril is an ACE inhibtor class drug used in the treatment of hypertension and heart failure. It belongs to the angiotensin-converting enzyme inhibitors (ACE inhibitors) class of drugs. It is a prodrug that is hydrolyzed after absorption to its main metabolite cilazaprilat. It is branded as Inhibace in Canada and other countries, Vascace and Dynorm in a number of European countries, among many other names. None of these varieties are available in the United States. Cilazapril is a pyridazine ACE inhibitor. It competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. As angiotensin II is a vasoconstrictor and a negative feedback mediator for renin activity, lower angiotensin II levels results in a decrease in blood pressure, an increase in renin activity, and stimulation of baroreceptor reflex mechanisms. Kininase II, an enzyme which degrades the vasodilator bradykinin, is identical to ACE and may also be inhibited.
Dược Động Học :
▧ Absorption :
Maximum plasma concentrations of cilazaprilat are reached within two hours after administration of cilazapril.
▧ Protein binding :
Maximum ACE inhibition is greater than 90% after 1 to 5 mg cilazapril. Maximum ACE inhibition is 70 to 80% after 0.5 mg cilazapril. Dose proportionality is observed following the administration of 1 to 5 mg cilazapril. Apparent non-proportionality is observed at 0.5 mg reflective of the binding to ACE. The higher doses of cilazapril are associated with longer duration of maximum ACE inhibition.
▧ Route of Elimination :
Cilazaprilat is eliminated unchanged by the kidneys. The total urinary recovery of cilazaprilat after intravenous administration of 2.5 mg is 91%.
▧ Half Life :
Half-lives for the periods 1 to 4 hours and 1 to 7 days after the intravenous administration of 2.5 mg cilazaprilat are 0.90 and 46.2 hours respectively.
▧ Clearance :
Total clearance is 12.3 L/h and renal clearance is 10.8 L/h. The total urinary recovery of cilazaprilat following the oral administration of 2.5 mg cilazapril is 52.6%.
Độc Tính : Limited data are available with regard to overdosage in humans. The most likely manifestations are hypotension, which may be severe, hyperkalaemia, hyponatraemia and renal impairment with metabolic acidosis. Treatment should be mainly symptomatic and supportive.
Chỉ Định : Cilazapril is an ACE inhibtor class drug used in the treatment of hypertension and heart failure.
Tương Tác Thuốc :
  • Amiloride Increased risk of hyperkalemia
  • Drospirenone Increased risk of hyperkalemia
  • Lithium The ACE inhibitor increases serum levels of lithium
  • Potassium Increased risk of hyperkalemia
  • Spironolactone Increased risk of hyperkalemia
  • Tizanidine Tizanidine increases the risk of hypotension with the ACE inhibitor
  • Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
  • Triamterene Increased risk of hyperkalemia
Liều Lượng & Cách Dùng : Tablet, film coated - Oral - 0.5 mg
Tablet, film coated - Oral - 1.0 mg
Tablet, film coated - Oral - 2.5 mg
Tablet, film coated - Oral - 5.0 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Roche
    Sản phẩm biệt dược : Dynorm
  • Công ty : Roche
    Sản phẩm biệt dược : Inhibace
  • Công ty : Teva
    Sản phẩm biệt dược : Inhibestril
  • Công ty : Roche
    Sản phẩm biệt dược : Vascace
  • Công ty : Mylan
    Sản phẩm biệt dược : Zapril
  • Công ty : Hemofarm
    Sản phẩm biệt dược : Zobox
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01340
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D07699
PharmGKB
http://www.pharmgkb.org/drug/PA164748302
Wikipedia
http://en.wikipedia.org/wiki/Cilazapril
Drugs.com
http://www.drugs.com/international/cilazapril.html
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