Doxofylline is not just another theophylline!

Figures & data

Figure 1 Bidimensional and tridimensional chemical structure images of theophylline and doxofylline.

Table 1 Comparison between doxofylline and theophylline

Doxofylline	Theophylline
No significant effect on any of the known PDE isoforms, no significant adenosine receptor antagonism, no direct effect on HDACs, interaction with β2-adrenoceptors	Non-selective inhibition of PDEs, inhibition of PI3K-δ, adenosine receptor antagonism and increased activity of certain HDACs
No inhibition of TNF-induced IL-8 secretion in ASM cells	Inhibition of TNF-induced IL-8 secretion in ASM cells
Low secretagogue activity	Increased gastric acid secretion and smooth muscle relaxation
Cardiac safety proved	Adverse cardiac effects caused by adenosine antagonism
Sleep architecture and quality minimally affected probably due to its lower affinity to the adenosine receptors	Sleep architecture and quality substantially and significantly disrupted
Lack of interference with the cytochrome enzymes	Interference with the cytochrome enzymes CYP1A2, CYP2A13, CYP1A1, CYP2E1,
CYP1A2, CYP2E1 and CYP3A4	CYP2D6 and CYP3A
No known drug interactions	Interactions with many drugs, including cimetidine, phenytoin, macrolides, fluoroquinolones, calcium-channel blockers, fluconazole, rifampin
No known food interactions	High-protein diet has been demonstrated to increase theophylline clearance by 30%
No monitoring of plasma levels necessary	Monitoring of plasma levels obligatory

Abbreviations: ASM, airway smooth muscle; IL, interleukin; HDACs, histone deacetylases; PDE, phosphodiesterase; TNF, tumor necrosis factor.