BRONCHOWIN TABLETS

Indications

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Bronchospasm

Dosage

Children: Refer to the BNF for Children for specific

Adults: Refer to the BNF for specific dosing guidance.

Mechanism of action

The main mechanism of action of doxofylline is thought to arise from the inhibition of phosphodiesterase activity, leading to increased levels of cAMP, which promotes smooth muscle relaxation. Doxofylline interacts with beta-2 adrenoceptors, with critical binding sites identified on serine residues 169 and 173, resulting in blood vessel and airway smooth muscle relaxation. Additionally, doxofylline may exert anti-inflammatory actions by reducing pleurisy induced by platelet activating factor (PAF) and inhibiting leukocyte migration across endothelial cells.

Pharmacodynamics

Doxofylline demonstrates potent bronchodilator activity comparable to that of theophylline. It has been shown to attenuate bronchoconstriction and inflammatory responses during challenges with PAF. Unlike theophylline, doxofylline does not inhibit histone deacetylase enzymes or act on various adenosine receptors at therapeutic concentrations. It has a specific action against PDE2A1 and exhibits antagonistic properties at adenosine A2A receptors at higher concentrations. Importantly, doxofylline can decrease airway responsiveness without affecting heart rate or respiratory rate.

Pharmacokinetics

Doxofylline's pharmacokinetic profile includes absorption, distribution, metabolism, and excretion characteristics typical of methylxanthine compounds. However, specific data regarding its half-life, peak plasma concentration, and renal clearance are not detailed in the provided information. Generally, methylxanthines are known for their rapid absorption and metabolism, primarily through the liver, with excretion occurring via urine.

Pregnancy

There is limited data on the safety of doxofylline during pregnancy. Use only if clearly needed and after assessing potential benefits against risks.

Breast-feeding

Doxofylline is excreted in breast milk; caution is advised when administered to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets
• Oral solution

Mechanism of action

The main mechanism of action of doxofylline is unclear. One of the mechanisms of action of is thought to arise from the inhibition of phosphodiesterase activity thus increasing the levels of cAMP and promoting smooth muscle relaxation. The interaction of doxofylline with beta-2 adrenoceptors was demonstrated by a study using nonlinear chromatography, frontal analysis and molecular docking. Serine 169 and serine 173 residues in the receptor are thought to be critical binding sites for doxofylline where hydrogen bonds are formed. Via mediating the actions of beta-2 adrenoceptors, doxofylline induces blood vessel relaxation and airway smooth muscle relaxation. There is also evidence that doxofylline may exert anti-inflammatory actions by reducing the pleurisy induced by the inflammatory mediator platelet activating factor (PAF) according to a rat study. It is suggested that doxofylline may play an important role in attenuating leukocyte diapedesis, supported by mouse preclinical studies where doxofylline administration was associated with inhibited leukocyte migration across vascular endothelial cells in vivo and in vitro.Unlike theophylline, doxofylline does not inhibit tumor necrosis factor-induced interleukin (IL)-8 secretion in ASM cells.

Pharmacodynamics

Doxofylline is a methylxanthine bronchodilator with potent bronchodilator activity comparable to that of theophylline. In animal studies, doxofylline demonstrated to attenuate bronchoconstriction, inflammatory actions and the release of thromboxane A2 (TXA2) when challenged with platelet-activating factor. Doxofylline does not demonstrate direct inhibition of any histone deacetylase (HDAC) enzymes or known PDE enzyme isoforms and did not act as an antagonist at A2 or A2 receptors. The affinity for adenosine A1, A2A and A2B receptors are reported to be all higher than 100 µM. It only displays an inhibitory action against PDE2A1 and antagonism at adenosine A(2A) at high concentrations. A study demonstrated that doxofylline interacts with β2-adrenoceptors to induce blood vessel relaxation and airway smooth muscle relaxation. In dog studies, doxofylline decreased airway responsiveness at a dose that did not affect heart rate and respiratory rate.