Biomaterial Database

Dornase alfa. A review of its pharmacological properties and therapeutic potential in cystic fibrosis. 1994

H M Bryson, and E M Sorkin

Adis International Limited, Auckland, New Zealand.

By cleaving neutrophil-derived DNA present in the infected lungs of patients with cystic fibrosis (CF), dornase alfa (recombinant human deoxyribonuclease I) reduces the adhesiveness and viscoelasticity of CF sputum. Well designed clinical studies performed in patients with CF and mild to moderate pulmonary disease [forced vital capacity (FVC) > or = 40% of predicted value] show that aerosolised dornase alfa improves lung function, achieving a 6 to 7% increase from baseline in forced expiratory volume in 1 second (FEV1) after 6 months' therapy. Improvements in general well-being and CF-related symptoms were also noted by patients. Importantly, dornase alfa reduced the relative risk of respiratory exacerbations requiring parenteral antibiotics by 22 to 34% compared with placebo. Short term studies with dornase alfa in patients with more severe pulmonary disease (FVC < 40% of predicted value) and in those with acute infectious exacerbations did not reveal any significant improvements in pulmonary function, although long term studies are required to fully determine efficacy. Voice alteration, laryngitis or rash may develop with dornase alfa therapy, although more clinical experience with the agent is required to define its tolerability profile. Anaphylaxis has not been reported with dornase alfa to date. In summary, aerosolised dornase alfa offers modest improvements in lung function and, importantly, a reduced risk of respiratory exacerbations in patients with CF and an FVC > or = 40% of the predicted value, thus representing an important adjunct agent in this patient group.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D003550	Cystic Fibrosis	An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION.	Mucoviscidosis,Cystic Fibrosis of Pancreas,Fibrocystic Disease of Pancreas,Pancreatic Cystic Fibrosis,Pulmonary Cystic Fibrosis,Cystic Fibrosis, Pancreatic,Cystic Fibrosis, Pulmonary,Fibrosis, Cystic,Pancreas Fibrocystic Disease,Pancreas Fibrocystic Diseases
D003850	Deoxyribonuclease I	An enzyme capable of hydrolyzing highly polymerized DNA by splitting phosphodiester linkages, preferentially adjacent to a pyrimidine nucleotide. This catalyzes endonucleolytic cleavage of DNA yielding 5'-phosphodi- and oligonucleotide end-products. The enzyme has a preference for double-stranded DNA.	DNase I,Streptodornase,DNA Endonuclease,DNA Nicking Enzyme,DNAase I,Dornavac,Endonuclease I,Nickase,Pancreatic DNase,T4-Endonuclease II,T7-Endonuclease I,Thymonuclease,DNase, Pancreatic,Endonuclease, DNA,T4 Endonuclease II,T7 Endonuclease I
D005100	Expectorants	Agents that increase mucous excretion. Mucolytic agents, that is drugs that liquefy mucous secretions, are also included here.	Expectorant,Mucolytic,Mucolytic Agent,Mucolytic Agents,Mucolytics,Agent, Mucolytic,Agents, Mucolytic
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000336	Aerosols	Colloids with a gaseous dispersing phase and either liquid (fog) or solid (smoke) dispersed phase; used in fumigation or in inhalation therapy; may contain propellant agents.	Aerosol
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D013183	Sputum	Material coughed up from the lungs and expectorated via the mouth. It contains MUCUS, cellular debris, and microorganisms. It may also contain blood or pus.	Sputum, Induced,Induced Sputum,Induced Sputums,Sputums,Sputums, Induced
D016032	Randomized Controlled Trials as Topic	Works about clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table.	Clinical Trials, Randomized,Controlled Clinical Trials, Randomized,Trials, Randomized Clinical