Chemistry:Ecallantide
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| Trade names | Kalbitor |
| Other names | DX-88 |
| AHFS/Drugs.com | Monograph |
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| Routes of administration | Subcutaneous injection |
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| Pharmacokinetic data | |
| Elimination half-life | 1.5–2.5 hours |
| Excretion | Kidney |
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| Chemical and physical data | |
| Formula | C305H442N88O91S8 |
| Molar mass | 7053.90 g·mol−1 |
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Ecallantide (trade name Kalbitor) is a drug used for the treatment of hereditary angioedema (HAE) and in the prevention of blood loss in cardiothoracic surgery.[1] It is an inhibitor of the protein kallikrein and a 60-amino acid polypeptide which was developed from a Kunitz domain through phage display to mimic antibodies inhibiting kallikrein.[1]
Medical uses
Angioedema
On November 27, 2009, ecallantide was approved by the FDA for the treatment of acute attacks of hereditary angioedema for persons over 16 years of age.[2] A single dose requires three separate injections, which are given under the skin.[3]
Ecallantide does not appear to be efficacious for the treatment of angioedema due to ACE inhibitors.[4][5]
Adverse effects
The most common adverse effects are headache, nausea, fatigue and diarrhea. Less common, but observed in more than 5% of patients in clinical trials, are respiratory tract infections, fever, vomiting, itching and upper abdominal pain. Up to 4% of patients showed anaphylaxis, which led to a black box warning in the US.[6]
Interactions
(As of 2011), no interaction studies have been conducted.[6]
Mechanism of action
HAE is caused by a mutation of the C1-inhibitor gene. Defective or missing C1-inhibitor permits activation of kallikrein, a protease that is responsible for liberating bradykinin from its precursor kininogen.[7][8] An excess of bradykinin leads to fluid leakage from blood vessels, causing swelling of tissues typical of HAE.
Ecallantide suppresses this pathogenetic mechanism by selectively and reversibly inhibiting the activity of plasma kallikrein.[6] Ecallantide's inhibitory constant (Ki) for kallikrein is 25 picoMolar, indicating high affinity.[9]
References
- ↑ 1.0 1.1 "Ecallantide (DX-88), a plasma kallikrein inhibitor for the treatment of hereditary angioedema and the prevention of blood loss in on-pump cardiothoracic surgery". Expert Opinion on Biological Therapy 8 (8): 1187–99. August 2008. doi:10.1517/14712598.8.8.1187. PMID 18613770.
- ↑ "FDA Approves Ecallantide for Hereditary Angioedema". Medscape. December 4, 2009. http://www.medscape.com/viewarticle/713401.
- ↑ 2013 Nurse's Drug Handbook (12th ed.). Burlington, MA: Jones & Bartlett Publishers. 2013. p. 391. ISBN 978-1-284-19536-1.
- ↑ "Ecallantide for the acute treatment of angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, controlled trial". Annals of Emergency Medicine 65 (2): 204–13. February 2015. doi:10.1016/j.annemergmed.2014.07.014. PMID 25182544.
- ↑ "Pharmacologic management of angioedema induced by angiotensin-converting enzyme inhibitors". American Journal of Health-System Pharmacy 73 (12): 873–9. June 2016. doi:10.2146/ajhp150482. PMID 27261237.
- ↑ 6.0 6.1 6.2 Dyax Corp. (2009). "Full prescibing information Kalbitor". http://www.kalbitor.com/pdf/KalbitorFullPrescribingInformation.pdf.
- ↑ "Bioregulation of kinins: kallikreins, kininogens, and kininases". Pharmacological Reviews 44 (1): 1–80. March 1992. PMID 1313585.
- ↑ Encyclopedia of Molecular Pharmacology. Springer. 2008. pp. 673–. ISBN 978-3-540-38916-3. https://books.google.com/books?id=iwwo5gx8aX8C&pg=PA673. Retrieved 11 December 2010.
- ↑ "NCATS Inxight: Drugs — ECALLANTIDE" (in en). National Center for Advancing Translational Sciences (NCATS). https://drugs.ncats.io/substance/5Q6TZN2HNM.
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