Inhaled theophylline: old drug new tricks?

Abstract

Theophylline and aminophylline (i.e., the soluble complex of theophylline with ethylenediamine) have been used in the treatment of respiratory diseases such as asthma and chronic obstructive pulmonary disease for more than 90 years. Theophylline’s narrow therapeutic index and side effects, as well as the discovery of more potent and safer bronchodilators, made it to fall out of favour with healthcare professionals and patients. New scientific knowledge on the molecular mechanism of action of theophylline, along with increasing clinical evidence suggest that theophylline should be exploited as an anti-inflammatory agent rather than a bronchodilator. This review covers the journey of theophylline from rise to fall and back to its potential re-emergence as a combination formulation with inhaled corticosteroids in the management of chronic inflammatory lung diseases. Several approaches to formulate theophylline either as a monotherapy or as a combination therapy for delivery to the lungs are presented.