Identification | |||||||||||||||||||||
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Name | Icatibant | ||||||||||||||||||||
Accession Number | DB06196 | ||||||||||||||||||||
Type | small molecule | ||||||||||||||||||||
Description | 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. | ||||||||||||||||||||
Structure |
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Categories (*) | |||||||||||||||||||||
Molecular Weight | 1304.522 | ||||||||||||||||||||
Groups | approved | ||||||||||||||||||||
Monoisotopic Weight | 1303.660794719 | ||||||||||||||||||||
Pharmacology | |||||||||||||||||||||
Indication | Approved for use in acute attacks of hereditary angioedema (HAE). Investigated for use/treatment in angioedema, liver disease, and burns and burn infections. | ||||||||||||||||||||
Mechanism of action | 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. | ||||||||||||||||||||
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. | ||||||||||||||||||||
Protein binding | Not Available | ||||||||||||||||||||
Biotransformation | 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) | ||||||||||||||||||||
Toxicity | Not Available | ||||||||||||||||||||
Affected organisms |
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Interactions | |||||||||||||||||||||
Drug Interactions |
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Food Interactions | Not Available |
B2 bradykinin receptor | |
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Name | B2 bradykinin receptor |
Gene Name | BDKRB2 |
Pharmacological action | yes |
Actions | antagonist |
References |
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DTHybrid score | 1.3927 |
Aminopeptidase N | |
Name | Aminopeptidase N |
Gene Name | ANPEP |
Pharmacological action | unknown |
Actions | inhibitor |
References |
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DTHybrid score | 1.0811 |
Id | Partner name | Gene Name | Score |
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6843 | Aminopeptidase N | pepN | 1.0811 |
890 | Niemann-Pick C1-like protein 1 | NPC1L1 | 0.0654 |
117 | Sterol O-acyltransferase 1 | SOAT1 | 0.0514 |
6176 | UDP-glucuronosyltransferase 1-3 | UGT1A3 | 0.0294 |
6178 | UDP-glucuronosyltransferase 2B7 | UGT2B7 | 0.0275 |
1709 | Canalicular multispecific organic anion transporter 2 | ABCC3 | 0.0274 |
6022 | UDP-glucuronosyltransferase 1-1 | UGT1A1 | 0.0268 |
1490 | Solute carrier organic anion transporter family member 1B1 | SLCO1B1 | 0.0242 |
1732 | ATP-binding cassette sub-family G member 2 | ABCG2 | 0.0225 |
1735 | Canalicular multispecific organic anion transporter 1 | ABCC2 | 0.0224 |
1588 | Multidrug resistance protein 1 | ABCB1 | 0.0174 |
4512 | Cytochrome P450 3A4 | CYP3A4 | 0.0153 |