Cilomilast: Orally Active Selective Phosphodiesterase-4 Inhibitor for Treatment of Chronic Obstructive Pulmonary Disease

Shaunta' D Martina, PharmD; Maha S Ismail; Kimi S Vesta, PharmD BCPS


The Annals of Pharmacotherapy. 2006;40(10):1822-1828. 

In This Article

Abstract and Introduction


Objective: To review available literature evaluating the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of cilomilast, a selective phosphodiesterase-4 (PDE4) inhibitor.
Data Sources: Literature was accessed through MEDLINE (1966-May 2006), Current Contents Clinical Medicine (1998-May 2006), and The Cochrane Library Database (1st quarter 2006) using the terms cilomilast, Ariflo, and SB 207 499. Reference lists from retrieved articles and information from the manufacturer were manually reviewed.
Study Selection And Data Extraction: All clinical trials evaluating cilomilast and published in English were included in this review. In addition, articles evaluating the pharmacology, pharmacokinetics, and safety of cilomilast in humans were reviewed.
Data Synthesis: Cilomilast is a second-generation PDE4 inhibitor with antiinflammatory effects that target bronchoconstriction, mucus hypersecretion, and airway remodeling associated with chronic obstructive pulmonary disease (COPD). Selective PDE4 inhibition is proposed to maximize the antiinflammatory effects of PDE inhibition while minimizing the adverse effects of nonselective agents. To date, 4 clinical trials have evaluated the efficacy of cilomilast and demonstrated improvement in lung function (forced expiratory volume in 1 second) and quality of life and reduction in the occurrence of COPD exacerbations compared with placebo. Cilomilast is generally well tolerated, with adverse effects being overall mild and self-limiting.
Conclusions: COPD is a progressive disease, and available treatment options provide limited efficacy. Given its unique mechanism of action and improved adverse effect profile compared with previous agents, cilomilast may have a promising role for the management of COPD.


Phosphodiesterase (PDE) inhibitors, such as theophylline, have been used to treat chronic obstructive pulmonary disease (COPD) for decades; however, the clinical benefits of these agents have never been established to out-weigh the risks of their numerous adverse effects.[1,2] The identification of several distinct PDE isoenzymes has led to the discovery of medications with safer risk-to-benefit profiles, including cilomilast.[3] This article reviews available literature evaluating the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of cilomilast (Ariflo, GlaxoSmithKline), a selective PDE4 inhibitor. Currently, cilomilast is in Phase III clinical trials and is not approved in the US. The Food and Drug Administration (FDA) issued an approvable letter in October 2003 requesting additional safety and efficacy data from the manufacturer.


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