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| Primary information |
|---|
| ID | 10023 |
| Therapeutic ID | Th1003 |
| Protein Name | Dornase alfa |
| Sequence | >Th1003_Dornase_alfa
LKIAAFNIQTFGETKMSNATLVSYIVQILSRYDIALVQEVRDSHLTAVGKLLDNLNQDAPDTYHYVVSEPLGRNSYKERYLFVYRPDQVSAVDSYYYDDGCEPCGNDTFNREPAIVRFFSRFTEVREFAIVPLHAAPGDAVAEIDALYDVYLDVQEKWGLEDVMLMGDFNAGCSYVRPSQWSSIRLWTSPTFQWLIPDSADTTATPTHCAYDRIVVAGMLLRGAVVPDSALPFNFQAAYGLSDQLAQAISDHYPVEVMLK
|
| Molecular Weight | 29253.9 |
| Chemical Formula | C1321H1999N339O396S9 |
| Isoelectric Point | 4.58 |
| Hydrophobicity | -0.083 |
| Melting point | 67 |
| Half-life | NA |
| Description | It is a biosynthetic form of human enzyme DNase I, produced in genetically modified CHO cells using recombinant DNA technology. The 260 amino acid synthetic sequence of dornase alfa is identical to the endogenous human enzyme. Dornase alfa cleaves extracellular DNA to 5´-phosphodinucleotide and 5´-phospho-oligonucleotide end products(without affecting intracellular DNA). In individuals with cystic fibrosis, extracellular DNA, an extremely viscous anion, is released by degenerating leukocytes which accumulate during inflammatory responses to infections. Enzymatic breakdown of this extracellular DNA causes reduction in sputum viscosity and viscoelasticity. |
| Indication/Disease | Used in the treatment of cystic fibrosis as adjunct therapy. |
| Pharmacodynamics | Cystic fibrosis (CF) is characterized by retention of viscous purulent secretions in the airways. These thick secretions contribute to reduced pulmonary function and to frequent pulmonary infection. Purulent pulmonary secretions of individuals with cystic fibrosis contain very high concentrations of extracellular DNA released by degenerating leukocytes that accumulate in response to these infections. Dornase alfa hydrolyzes the DNA in sputum of CF patients and reduces sputum viscosity and viscoelasticity. The enzyme does not appear to affect sputum in the absence of an inflammatory response to infection, nor does it affect the sputum of healthy individuals. |
| Mechanism of Action | Dornase alfa is a biosynthetic form of human DNase I. The enzyme is involved in endonucleolytic cleavage of extracellular DNA to 5´-phosphodinucleotide and 5´-phospho-oligonucleotide end products. It has no effect on intracellular DNA. Optimal activity dependent on the presence of divalent cations such as calcium and magnesium. Extracellular DNA is a viscous anionic polymer and its breakdown appears to improve the viscosity and viscoelasticity of purulent sputum of individuals with CF. |
| Toxicity | Adverse reactions occur at a rate of 1/1000 and are usually mild and transient in nature. Reported adverse effects include decreased lung function, rash, urticaria, chest pain (pleuritic/non-cardiac), dyspepsia, voice alteration (hoarseness), pharyngitis, |
| Metabolism | NA |
| Absorption | Systemic absorption is undetectable when administered via inhalation. |
| NA |
| Clearance | NA |
| Categories | Amino Acids, Peptides, and Proteins, Cough and Cold Preparations, Decreased Respiratory Secretion Viscosity, Deoxyribonucleases, Endodeoxyribonucleases, Endonucleases, Enzymes, Enzymes and Coenzymes, Esterases, Expectorants, Hydrolases, Proteins, Recombinant Human Deoxyribonuclease 1 |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | Exubera (insulin inhalation, rapid acting) |
| Target | NA |
| Brand Name | NA |
| Company | Cardinal Health, Catalent Pharma Solutions, F Hoffmann-La Roche Ltd., Meda AB, Medpointe Pharmaceuticals |
| Brand Description | Cardinal Health, Catalent Pharma Solutions, F Hoffmann-La Roche Ltd., Meda AB, Medpointe Pharmaceuticals |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |