Doxofylline (also known as doxophylline) is a phosphodiesterase inhibiting

bronchodilator A bronchodilator or broncholytic (although the latter occasionally includes secretory inhibition as well) is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lun ...

used in the treatment of chronic respiratory diseases such as

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

and

COPD Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by chronic respiratory symptoms and airflow limitation. GOLD defines COPD as a heterogeneous lung condition characterized by chronic respiratory s ...

. Like

theophylline Theophylline, also known as 1,3-dimethylxanthine, is a drug that inhibits phosphodiesterase and blocks adenosine receptors. It is used to treat chronic obstructive pulmonary disease (COPD) and asthma. Its pharmacology is similar to other met ...

, it is a

xanthine Xanthine ( or , from Ancient Greek for its yellowish-white appearance; archaically xanthic acid; systematic name 3,7-dihydropurine-2,6-dione) is a purine base found in most human body tissues and fluids, as well as in other organisms. Several ...

derivative.

Medical uses

Doxophylline is used to treat chronic respiratory diseases such as

and

. In animal and human studies, it has shown similar efficacy to

but with significantly fewer side effects. In February 2014, the US

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

granted an

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

designation to doxofylline for the treatment of

bronchiectasis Bronchiectasis is a disease in which there is permanent enlargement of parts of the bronchi, airways of the lung. Symptoms typically include a chronic cough with sputum, mucus production. Other symptoms include shortness of breath, hemoptysis, co ...

following the submission of an application by Alitair Pharmaceuticals, in May 2013.

Pharmacology

Unlike other xanthines, doxofylline lacks any significant

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for

adenosine receptor The adenosine receptors (or P1 receptors) are a class of Purinergic receptor, purinergic G protein-coupled receptors with adenosine as the endogenous ligand (biochemistry), ligand. There are four known types of adenosine receptors in humans: Aden ...

s and does not produce

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

effects. This suggests that its antiasthmatic effects are mediated by another mechanism, perhaps its actions on

phosphodiesterase A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, ''phosphodiesterase'' refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many oth ...

. From a

pharmacokinetic Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific subs ...

point of view, doxofylline importantly differs from theophylline also because it lacks the ability to interfere with the cytochrome enzymes

CYP1A2 Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene. Function ...

CYP2E1 Cytochrome P450 2E1 (abbreviated CYP2E1, ) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, inclu ...

and

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

, thus preventing significant interaction with other drugs metabolized via these pathways in the liver. Concomitant treatment with certain other medications (including

allopurinol Allopurinol is a medication used to decrease hyperuricemia, high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It i ...

H2 receptor antagonist H2 antagonists, sometimes referred to as H2RAs and also called H2 blockers, are a class of medications that block the action of histamine at the histamine H2 receptors of the parietal cells in the stomach. This decreases the production of stom ...

s, lincosamide antibiotics,

macrolide antibiotics Macrolides are a class of mostly natural products with a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. Macrolides belong to the polyketide class of natural products. So ...

, and

propranolol Propranolol is a medication of the beta blocker class. It is used to treat hypertension, high blood pressure, some types of cardiac dysrhythmia, irregular heart rate, thyrotoxicosis, capillary hemangiomas, akathisia, performance anxiety, and ...

) can decrease the hepatic clearance of doxofylline, which can result in increased serum levels of doxofylline.

Names

It is marketed under many brand names worldwide, including: Xiva, An Li Nuo Er, An Sai Ma, Ansimar, Asima, Bestofyline, Chuan Ning, D-Fyal, Dilatair, Doxiba, Doxiva, Doxobid, Doxobron, Doxofilina, Doxofillina, Doxofyllin, Doxoll, Doxophylline, Doxovent, Doxyjohn, Fei Te Ai Si, Fixolin, Jian Fang Neng, Lang Ming, Lv Meng, Mai Ping Xi, Maxivent, Mucosma, Na De Lai, Phylex, Phyllin, Puroxan, Rexipin, Shu Zhi, Shuai An, Shuweixin, Suo Di, Suo Ji, Suo Li An, Xi Si Nuo, Xin Qian Ping, Xin Xi Ping, Yi Suo, and Yili. It is also marketed as a

combination drug A combination drug is a combination of two or more pharmaceutical drugs as active ingredients combined into a single dosage form, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. Fix ...

with

terbutaline Terbutaline, sold under the brand names Bricanyl and Marex among others, is a β2 adrenergic receptor agonist, used as a "reliever" inhaler in the management of asthma symptoms and as a tocolytic (anti- contraction medication) to delay preterm ...

as Doxoll-TL, Mucosma-T and Phylex-TR. It is also marketed as a combination drug with

montelukast Montelukast, sold under the brand name Singulair among others, is a medication used in the maintenance treatment of asthma. It is generally less preferred for this use than inhaled corticosteroids. It is not useful for acute asthma attacks. ...

as Doxoll-ML, Doxomont, Doxoril-M, Doxovent-M, Lunair-M, and Venidox-M.

Medical uses

Pharmacology

Names

References

Further reading