Doxofylline is not just another theophylline!

Abstract

Doxofylline, which differs from theophylline in containing the dioxalane group at position 7, has comparable efficacy to theophylline in the treatment of respiratory diseases, but with an improved tolerability profile and a favorable risk-to-benefit ratio. Furthermore, it does not have significant drug–drug interactions as exhibited with theophylline, which make using theophylline more challenging, especially in elderly patients with co-morbidities receiving multiple classes of drug. It is now clear that doxofylline also possesses a distinct pharmacological profile from theophylline (no significant effect on any of the known phosphodiesterase isoforms, no significant adenosine receptor antagonism, no direct effect on histone deacetylases, interaction with β2-adrenoceptors) and therefore, should not be considered as just a modified theophylline. Randomized clinical trials of doxofylline to investigate the use of this drug to reduce exacerbations and hospitalizations due to asthma or COPD as an alternative to expensive biologics, and certainly as an alternative to theophylline are to be encouraged.

Efficacy and safety profile of xanthines in COPD: a network meta-analysis

“…The results of the present meta-analysis are not surprising considering that doxofylline should not be assumed just as another theophylline [14]. It is now well established that doxofylline possesses a distinct pharmacological profile from theophylline (table 1 and figure S4).…”

“…Given the pharmacological profile of doxofylline [49,50]; its significant anti-inflammatory activity that can result in significant steroid sparing activity, as documented at least in both an allergic and a nonallergic murine model of lung inflammation [54]; its documented clinical activity [12][13][14]; and, above all, the results of the present meta-analysis, there is a clear need to understand what is the room in the treatment of COPD for a xanthine that induces the same, if not even better, therapeutic effects of theophylline but with a totally different safety profile. Specifically, the rate of study withdrawal due to adverse events such as dyspepsia, epigastralgia, nausea and palpitation was approximately four-fold higher in COPD patients treated with theophylline than in those treated with doxofylline.…”

“…There is evidence that doxofylline, at least, is an effective bronchodilator for relieving airway obstruction and displays a better safety profile than theophylline, having a favourable risk-to-benefit ratio [12][13][14]. These findings suggest that it could be an attractive alternative to theophylline in the treatment of patients with COPD.…”

The protective effect of doxofylline against lipopolysaccharides (LPS)-induced activation of NLRP3 inflammasome is mediated by SIRT1 in human pulmonary bronchial epithelial cells

“…Compared to theophylline, administration of doxofylline does not increase the frequency of cardiac events, and patients show improved tolerability and a favourable risk-to-benefit ratio. Thus, doxofylline has better efficacy and fewer side effects, making it a promising bronchodilator [11]. Preclinical research has shown that doxofylline inhibits LPSinduced lung inflammation in mice [12].…”

“…Compared with theophylline, doxofylline has a dioxalane group at position 7. Doxofylline has improved efficacy as compared to theophylline but shows fewer side effects and is viewed as a replacement for theophylline [11]. Doxofylline possesses potent anti-inflammatory and bronchodilatory activities, and it acts as a non-selective phosphodiesterase (PDE) inhibitor.…”