Ecallantide

• CAS Number: 460738-38-9

Ecallantid (DX -88 ) is a drug which is used in the treatment of hereditary angioedema. This belongs to the group of Kunitz domain peptides biopharmaceuticals is an inhibitor (inhibitor ) of the enzyme kallikrein. In 2009 Ecallantid was approved by the U.S. FDA and has since been distributed in the U.S. by the pharmaceutical company Dyax under the brand name Kalbitor ™. An authorization for the European market is still pending.

• 2.1 pharmacodynamics ( mode of action )
• 2.2 pharmacokinetics

Clinical information

Areas of application (indications )

Ecallantid is approved for the U.S. market for the treatment of over 16 - year-old patient with hereditary angioedema. This is a rare inherited disorder characterized by severe and often painful swelling in the abdomen ( tummy), the face may occur on the hands and in the airways.

Contraindications ( contraindications)

Ecallantid should not be used in patients with a known hypersensitivity to the active substance. In clinical trials responded up to 4 % of patients with signs of an anaphylactic reaction.

Interactions

The potential interactions of Ecallantid with other drugs has no information. These have been studied clinically or experimentally.

Adverse drug reactions

In clinical safety studies in 255 patients frequent headaches, nausea, fatigue and diarrhea were observed as adverse drug reactions. At a frequency of about 5% and respiratory infections, fever, vomiting, upper abdominal pain and itching occurred. Sicherheitslimitierende hypersensitivity reactions, which are fed back to an endogenous immune response against Ecallantid could be observed in up to 4 % of patients.

Pharmacology

Pharmacodynamics ( mode of action )

Hereditary angioedema is a rare genetic condition. It is due to a mutation in the gene encoding the C1-esterase inhibitor. This endogenous inhibitor regulates various physiological signal transduction pathways, including the kallikrein -kinin pathway. At a key point of this signaling pathway bradykinin is cleaved from kininogen of inflammatory mediator. A dysfunction of C1 esterase inhibitor in the context of hereditary angioedema thus leads to the characteristic swelling in the abdomen, the face, the hands and the respiratory tract. Attacks that usually take 1-5 days are often jokingly and can be life-threatening laryngeal angioedema in appearance.

As a selective and reversible inhibitor of the enzyme kallikrein Ecallantid inhibits the production of bradykinin responsible for the swelling. Ecallantid thereby engages at a later date than the C1 esterase inhibitor in the kallikrein -kinin pathway.

Pharmacokinetics

Following subcutaneous administration of Ecallantid its maximum plasma concentration is reached after 2 to 3 hours. The plasma half-life is two hours. As a peptide having a molecular mass of about 7 kDa, the elimination is carried out mainly via the kidneys in the urine un.

Biochemistry

Ecallantid is one of 60 amino acids existing, genetically engineered peptide. With the aid of phage display has been out of a library of Kunitz domains, derived from those of tissue factor pathway inhibitor selected. As a production organism, the yeast species Pichia pastoris serves.