Site-specific phosphodiesterase (PDE) inhibition is now a standard component of pharmacotherapy. Because PDE5 is selectively located in the genital area, PDE5 inhibition (e.g., sildenafil, tadalafil, vardenafil) can improve circulatory flow and enhance sexual function. PDE3 is located dominantly in the circulation of the lower legs, enabling the PDE3 inhibitor cilostazol to improve circulation in patients with intermittent claudication. PDE6 is located in the retina, such that sildenafil (which has PDE5 and PDE6 inhibition activity) can produce blue visual effects. PDE4 is located in the pulmonary system, and PDE4 inhibition has recently been added to the pharmacotherapy of chronic obstructive pulmonary disease (COPD) in the form of roflumilast.
In the United States, roflumilast is FDA-approved for reducing COPD exacerbations. Although registration trials have shown modest bronchodilatory activity from PDE4 inhibition, the degree of bronchodilation produced by the PDE4 inhibitor roflumilast is below the threshold required by the FDA to be specifically labeled as a bronchodilator.
Ethnically diverse responses to pharmacotherapy are increasingly recognized to be of clinical significance. For instance, there are clinically meaningful differences in the metabolism of theophylline between American children and Chinese children. Zheng et al evaluated the effects of roflumilast treatment of COPD in an Asian population.
The efficacy of roflumilast in this all-Asian population was consistent with prior published results in non-Asian populations. Unless the current and evolving smoking status of much of Asia (especially men) experiences a prominent reversal — some recent reports indicate that as many as 50% of adult Chinese men are smokers — we can anticipate the need for a full complement of COPD treatments in the coming decades.