Study details problems with COPD drug
Roflumilast, a drug recently approved in the U.S. to treat severe chronic obstructive pulmonary disease (COPD), increases the production of a protein that causes inflammation – which possibly results in patients developing a tolerance to the drug after repeated use and renders it ineffective, according to a new study.
Roflumilast, a drug recently approved in the United States to treat severe chronic obstructive pulmonary disease (COPD), increases the production of a protein that causes inflammation-which possibly results in patients developing a tolerance to the drug after repeated use and renders it ineffective, according to a new study.
Researchers at Georgia State University, Kumamoto University and the University of Rochester Medical Center conducted the study, published in the March 23 edition of the Proceedings of the National Academy of Sciences, US.
Dr Li
"There is clinical evidence showing that patients could develop a tolerance if they keep taking repeated dosing of this drug, but why or how has been unknown. If we can figure out why people have a tolerance, we can probably improve the therapeutics," said Jian-Dong Li, MD, director of the Institute for Biomedical Sciences at Georgia State University, in a statement from GSU.
It is important to develop new therapeutics to improve the efficacy of roflumilast because there are no effective therapeutics for severe COPD, Dr Li said.
Roflumilast was designed to inhibit the enzymatic activity of a protein called PDE4, but the study found the drug also undergoes a complicated, unwanted process to increase the production of PDE4B2. The surge of this protein increases inflammation in ways that are dependent and independent of enzymatic activity and may contribute to the patient developing a tolerance to roflumilast.
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The researchers concluded the drug, even at high concentrations, cannot fully suppress inflammation because it can't suppress inflammatory response that is independent of enzymatic activity.
The researchers also identified an important protein, called PKA-Cβ, which can be targeted to reduce the unwanted production of PDE4B2. In addition, they found that roflumilast works with the major bacterial pathogen that causes symptoms to worsen in severe COPD to increase production of the unwanted protein PDE4B2 in a synergistic manner.
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