Dornase alfa

Identification

Summary

Dornase alfa 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.

Brand Names

Pulmozyme

Generic Name

Dornase alfa

DrugBank Accession Number

DB00003

Background

Dornase alfa 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 alfa 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.

Type

Biotech

Groups

Approved

Biologic Classification

Protein Based Therapies
Recombinant Enzymes

Protein Structure

Protein Chemical Formula: C₁₃₂₁H₁₉₉₉N₃₃₉O₃₉₆S₉
Protein Average Weight: 29253.9 Da

Sequences

>Dornase alfa sequence
LKIAAFNIQTFGETKMSNATLVSYIVQILSRYDIALVQEVRDSHLTAVGKLLDNLNQDAP
DTYHYVVSEPLGRNSYKERYLFVYRPDQVSAVDSYYYDDGCEPCGNDTFNREPAIVRFFS
RFTEVREFAIVPLHAAPGDAVAEIDALYDVYLDVQEKWGLEDVMLMGDFNAGCSYVRPSQ
WSSIRLWTSPTFQWLIPDSADTTATPTHCAYDRIVVAGMLLRGAVVPDSALPFNFQAAYG
LSDQLAQAISDHYPVEVMLK

Download FASTA Format

Synonyms

Deoxyribonuclease (human clone 18-1 protein moiety)
Dornasa alfa
Dornase alfa
Dornase alfa, recombinant
Dornase alpha
Recombinant deoxyribonuclease (DNAse)

Poor quality drug data slowing you down?

Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.

Download eBook

Poor quality drug data slowing you down?

Download eBook

Pharmacology

Indication

Used as adjunct therapy in the treatment of cystic fibrosis.

Reduce drug development failure rates

Build, train, & validate machine-learning models
with evidence-based and structured datasets.

See how

Build, train, & validate predictive machine-learning models with structured datasets.

See how

Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Used in combination to manage	Cystic fibrosis		••••••••••••			••••••••

Contraindications & Blackbox Warnings

Prevent Adverse Drug Events Today

Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.

Learn more

Avoid life-threatening adverse drug events with our Clinical API

Learn more

Pharmacodynamics

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 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´-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 alfa does not seem to have any effect on non-purulent sputum.

Target	Actions	Organism
ADNA	Not Available	Humans

Absorption

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 alfa 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.

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.

Protein binding

Not Available

Metabolism

While no conclusive studies have yet been published, dornase alfa is expected to be metabolized by proteases in biofluids.

Route of elimination

Not Available

Half-life

Not Available

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.

Adverse Effects

Improve decision support & research outcomes

With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!

See the data

Improve decision support & research outcomes with our structured adverse effects data.

See a data sample

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.

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions: This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
No interactions found.
Food Interactions: No interactions found.

Products

Drug product information from 10+ global regions

Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.

Access now

Access drug product information from over 10 global regions.

Access now

International/Other Brands

Viscozyme (Roche (Chile))

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Pulmozyme	Solution	1 mg/1mL	Respiratory (inhalation)	Genentech, Inc.	1993-12-30	Not applicable
Pulmozyme 1mg/ml	Solution	1 mg / mL	Respiratory (inhalation)	Hoffmann La Roche	1994-12-31	Not applicable

Chemical Identifiers

UNII: 953A26OA1Y
CAS number: 143831-71-4

References

General References

Cramer GW, Bosso JA: The role of dornase alfa in the treatment of cystic fibrosis. Ann Pharmacother. 1996 Jun;30(6):656-61. [Article]
Jones AP, Wallis C: Dornase alfa for cystic fibrosis. Cochrane Database Syst Rev. 2010 Mar 17;(3):CD001127. doi: 10.1002/14651858.CD001127.pub2. [Article]
Riethmueller J, Kumpf M, Borth-Bruhns T, Brehm W, Wiskirchen J, Sieverding L, Ankele C, Hofbeck M, Baden W: Clinical and in vitro effect of dornase alfa in mechanically ventilated pediatric non-cystic fibrosis patients with atelectases. Cell Physiol Biochem. 2009;23(1-3):205-10. doi: 10.1159/000204109. Epub 2009 Feb 18. [Article]

External Links

UniProt: P24855
Genbank: M55983
PubChem Substance: 46507792
RxNav: 337623
ChEMBL: CHEMBL1201431
Therapeutic Targets Database: DAP000981
PharmGKB: PA10318
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Dornase_alfa

FDA label

Download (131 KB)

MSDS

Download (10.4 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Completed	Basic Science	Cystic Fibrosis (CF)	1
4	Completed	Treatment	Atelectasis	1
4	Completed	Treatment	Cystic Fibrosis (CF)	2
4	Completed	Treatment	Empyema / Parapneumonic Effusion / Pleural Diseases / Pleural space infections	1
4	Completed	Treatment	Otitis Media (OM)	1

Pharmacoeconomics

Manufacturers

Genentech, Inc

Packagers

Cardinal Health
Catalent Pharma Solutions
F Hoffmann-La Roche Ltd.
Genentech Inc.
Meda AB
Medpointe Pharmaceuticals

Dosage Forms

Form	Route	Strength
Aerosol, spray	Respiratory (inhalation)	2.5 mg
Solution	Respiratory (inhalation)	1 mg/1mL
Solution	Respiratory (inhalation)	1 mg / mL
Solution	Respiratory (inhalation)	2.5 mg/2.5ml
Solution	Respiratory (inhalation)
Solution	Respiratory (inhalation)	2500 E./2.5ml
Solution	Respiratory (inhalation)	2.5 mg

Prices

Unit description	Cost	Unit
Pulmozyme 1 mg/ml Solution 2.5ml Plastic Container	77.06USD	plastic
Pulmozyme 1 mg/ml ampul	37.05USD	ml
Lufyllin 400 mg tablet	4.81USD	tablet
Lufyllin-400 tablet	4.62USD	tablet
Lufyllin-GG 200-200 mg tablet	3.99USD	tablet
Lufyllin-gg tablet	3.84USD	tablet
Lufyllin 200 mg tablet	3.21USD	tablet
Lufyllin-GG 100-100 mg/15ml Elixir	0.6USD	ml

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
CA2184581	No	2005-02-22	2015-02-28
CA2137237	No	2004-10-26	2013-05-28

Properties

State

Liquid

Experimental Properties

Property	Value	Source
melting point (°C)	67 °C	Chan, H.K. et al., Pharm Res. 13:756-761 (1996)
hydrophobicity	-0.083	Not Available
isoelectric point	4.58	Not Available

Targets

Build, predict & validate machine-learning models

Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.

Learn more

Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.

Learn more

Details1. DNA

Kind

Nucleotide

Organism

Humans

Pharmacological action

Yes

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

References

Cramer GW, Bosso JA: The role of dornase alfa in the treatment of cystic fibrosis. Ann Pharmacother. 1996 Jun;30(6):656-61. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55

Dornase alfa

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References