Tìm theo
Icatibant
Các tên gọi khác (1) :
  • HOE 140
anti inflammatory agents non steroidal, adrenergic beta antagonists
Thuốc Gốc
Small Molecule
CAS: 130308-48-4
ATC: B06AC02
CTHH: C59H89N19O13S
PTK: 1304.522
Icatibant (Firazyr) is a synthetic peptidomimetic drug consisting of ten amino acids, and acts as an effective and specific antagonist of bradykinin B2 receptors. It has been approved in the EU for use in hereditary angioedema, and is under investigation for a number of other conditions in which bradykinin is thought to play a significant role. Icatibant currently has orphan drug status in the United States and FDA approved on August 25, 2011.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
Phân tử khối
1304.522
Monoisotopic mass
1303.660794719
InChI
InChI=1S/C59H89N19O13S/c60-37(14-5-19-67-57(61)62)48(82)72-38(15-6-20-68-58(63)64)52(86)75-22-8-18-43(75)54(88)77-30-35(80)26-44(77)50(84)70-28-47(81)71-40(27-36-13-9-23-92-36)49(83)74-41(31-79)53(87)76-29-34-12-2-1-10-32(34)24-46(76)55(89)78-42-17-4-3-11-33(42)25-45(78)51(85)73-39(56(90)91)16-7-21-69-59(65)66/h1-2,9-10,12-13,23,33,35,37-46,79-80H,3-8,11,14-22,24-31,60H2,(H,70,84)(H,71,81)(H,72,82)(H,73,85)(H,74,83)(H,90,91)(H4,61,62,67)(H4,63,64,68)(H4,65,66,69)/t33-,35+,37+,38?,39-,40-,41-,42-,43?,44?,45?,46?/m0/s1
InChI Key
InChIKey=QURWXBZNHXJZBE-MCDGZUPGSA-N
IUPAC Name
(2S)-2-{[(3aS,7aS)-1-({2-[(2S)-2-[(2S)-2-(2-{[(4R)-1-[(1-{2-[(2R)-2-amino-5-[(diaminomethylidene)amino]pentanamido]-5-[(diaminomethylidene)amino]pentanoyl}pyrrolidin-2-yl)carbonyl]-4-hydroxypyrrolidin-2-yl]formamido}acetamido)-3-(thiophen-2-yl)propanamido]-3-hydroxypropanoyl]-1,2,3,4-tetrahydroisoquinolin-3-yl}carbonyl)-octahydro-1H-indol-2-yl]formamido}-5-[(diaminomethylidene)amino]pentanoic acid
Traditional IUPAC Name
icatibant
SMILES
[H][C@]12CC(N(C(=O)C3CC4=CC=CC=C4CN3C(=O)[C@H](CO)NC(=O)[C@H](CC3=CC=CS3)NC(=O)CNC(=O)C3C[C@@H](O)CN3C(=O)C3CCCN3C(=O)C(CCCN=C(N)N)NC(=O)[C@H](N)CCCN=C(N)N)[C@@]1([H])CCCC2)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O
Độ hòa tan
1 mg/mL
logP
-8
logS
-4.4
pKa (strongest acidic)
3.46
pKa (Strongest Basic)
11.45
PSA
523.72 Å2
Refractivity
332.91 m3·mol-1
Polarizability
137.03 Å3
Rotatable Bond Count
30
H Bond Acceptor Count
23
H Bond Donor Count
15
Physiological Charge
3
Number of Rings
7
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : Icatibant is a potent, specific, competitive, and selective peptidomimetic bradykinin beta2-receptor antagonist (pA2 = 9.04). It has a modified peptide structure, and is the first bradykinin receptor antagonist to act on the guinea-pig trachea without demonstrating agonist effects. It also inhibits aminopeptidase N (Ki = 9.1 μM). If an IV dose of 0.4 and 0.8 mg/kg was infused over 4 hours, one may observe an inhibited response to bradykinin challenge for 6 - 8 hours following completion of infusion.
Cơ Chế Tác Dụng : Icatibant (Firazyr) is a synthetic peptidomimetic drug consisting of ten amino acids, and acts as an effective and specific antagonist of bradykinin B2 receptors. It has been approved in the EU for use in hereditary angioedema, and is under investigation for a number of other conditions in which bradykinin is thought to play a significant role. Icatibant currently has orphan drug status in the United States and FDA approved on August 25, 2011. Bradykinin is a peptide-based hormone that is formed locally in tissues, very often in response to a trauma. It increases vessel permeability, dilates blood vessels and causes smooth muscle cells to contract. Bradykinin plays an important role in the mediation of pain. Surplus bradykinin is responsible for the typical symptoms of inflammation, such as swelling, redness, overheating and pain. These symptoms are mediated by activation of bradykinin B2 receptors. In patients with HAE, they have an absent or dysfunctional C1-esterase inhibitor. This inhibitor is responsible for the production of bradykinin in which displacement of bradykinin from B2 receptors by icatibant has an inhibitory effect on the receptor for a relatively long time.
Dược Động Học :
▧ Absorption :
The absolute bioavailability of icatibant following a 30 mg subcutaneous dose is approximately 97%. Maximum plasma concentrations (Cmax) of 974 ± 280 ng/mL was reached when a single subcutaneous dose of 30 mg was administered. The AUC was 2165 ± 568 ng∙hr/mL. Icatibant did not accumulate following multiple doses.
▧ Volume of Distribution :
Vdss, subcutaneous injection = 29.0 ± 8.7 L.
▧ Metabolism :
Icatibant is metabolized by proteolytic enzymes into inactive metabolites. The cytochrome P450 enzyme system is not involved with the metabolism of icatibant.
▧ Route of Elimination :
Urine (<10% unchanged)
▧ Half Life :
After subcutaneous administration, mean elimination half-life was 1.4 ± 0.4 hours.
▧ Clearance :
Plasma clearance following subcutaneous administration was 245 ± 58 mL/min.
Chỉ Định : Approved for use in acute attacks of hereditary angioedema (HAE). Investigated for use/treatment in angioedema, liver disease, and burns and burn infections.
Tương Tác Thuốc :
  • Benazepril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
  • Captopril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
  • Enalapril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
  • Fosinopril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
  • Moexipril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
  • Perindopril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
  • Quinapril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
  • Ramipril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
  • Trandolapril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
Liều Lượng & Cách Dùng : Solution - Subcutaneous - 30 mg/3 mL
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty : Shire
    Sản phẩm biệt dược : Firazyr
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