Dornase Alpha

Dornase Alpha Uses, Dosage, Side Effects, Food Interaction and all others data.

Dornase Alpha is a biosynthetic form of human deoxyribunuclease I (DNase I) enzyme. It is produced in genetically modified Chinese hamster ovary (CHO) cells using recombinant DNA technology. The 260-amino acid sequence of dornase alfa is identical to the endogenous human enzyme. Dornase Alpha cleaves extracellular DNA to 5´-phosphodinucleotide and 5´-phosphooligonucleotide end products without affecting intracellular DNA. In individuals with cystic fibrosis, extracellular DNA, which is an extremely viscous anion, is released by degenerating leukocytes that accumulate during inflammatory responses to infections. Enzymatic breakdown of this extracellular DNA appears to reduce sputum viscosity and viscoelasticity.

Cystic fibrosis (CF) is a disease characterized by the retention of viscous purulent secretions in the airways. These thick secretions contribute both 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 Alpha 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.

Trade Name Dornase Alpha
Generic Dornase alfa
Dornase alfa Other Names Deoxyribonuclease (human clone 18-1 protein moiety), Dornasa alfa, Dornase alfa, Dornase alfa, recombinant, Dornase alpha, Recombinant deoxyribonuclease (DNAse)
Type
Formula C1321H1999N339O396S9
Weight 29253.9 Da
Groups Approved
Therapeutic Class
Manufacturer
Available Country
Last Updated: September 19, 2023 at 7:00 am
Dornase Alpha
Dornase Alpha

Uses

Dornase Alpha is a synthetic form of human deoxyribonuclease I used to break down extracellular DNA in the lungs, a major source of mucous viscosity in cystic fibrosis.

Used as adjunct therapy in the treatment of cystic fibrosis.

Dornase Alpha is also used to associated treatment for these conditions: Cystic Fibrosis (CF)

How Dornase Alpha works

Dornase Alpha is a biosynthetic form of human DNase I. The enzyme is involved in endonucleolytic cleavage of extracellular DNA to 5´-phosphodinucleotide and 5´-phosphooligonucleotide end products. It has no effect on intracellular DNA. Optimal activity is 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, thus reducing airflow obstruction. Dornase Alpha does not seem to have any effect on non-purulent sputum.

Toxicity

Adverse reactions occur at a frequency of < 1/1000 and are usually mild and transient in nature. Reported adverse effects include chest pain (pleuritic/non-cardiac), fever, dyspepsia, voice alteration (hoarseness), pharyngitis, dyspnea, laryngitis, rhinitis, decreased lung function, rash, urticaria, and conjunctivitis. There is no evidence of carcinogenic or mutagenic properties. The safety of dornase alfa has not been studied in pregnant women, nursing women and children under the age of 5 years old.

Food Interaction

No interactions found.

Volume of Distribution

In studies in rats and monkeys, the initial volume of distribution is similar to the serum volume. Concentrations in sputum decline rapidly after inhalation.

Elimination Route

Studies in rats and monkeys after inhalation of dornase alfa shows very little systemic absorption (less than 15% for rats and less than 2% for monkeys). The results were also witnessed in patients. Dornase Alpha is also associated with very low accumulation with no serum concentration greater than 10ng/mL observed no matter the dose administered. Bioavailability: mean sputum concentrations of dornase alfa can be measured after 15 minutes. Onset is achieved within 3 to 7 days. Peak concentrations are achieved after 9 days.

Clearance

Studies in rats indicate that, following aerosol administration, the disappearance half-life of dornase alfa from the lungs is 11 hours. In humans, sputum DNase levels declined below half of those detected immediately post-administration within 2 hours but effects on sputum rheology persisted beyond 12 hours.

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