The pharmokinetic limitations of antioxidant treatment for COPD.
COPD is one of the leading causes of death worldwide and the age-adjusted mortality for this disease has risen significantly over the past 30 years. Current pharmacological treatments do not effectively address the inflammatory and apoptotic mechanisms that are critical in the development of this disease. Thus, despite therapy, patients typically experience a continued deterioration of their clinical status. Markers of oxidative stress are increased in the lungs of COPD patients and epidemiologic and animal studies indicate that antioxidants can protect the lungs from the damaging effects of cigarette smoke. To date, however, clinical trials of antioxidants for COPD have yielded disappointing results. This review discusses the pharmokinetic factors that limit the use of exogenous antioxidants as a treatment for this disease. In addition, it addresses strategies to overcome these limitations so that the beneficial properties of antioxidants can be translated into effective therapies for COPD patients.
Department of Medicine, Columbia University, New York, NY 10032, USA.
Robert
R
Foronjy
Alison
A
Wallace
Jeanine
J
D'Armiento
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000975:Antioxidants; D014409:Tumor Necrosis Factor-alpha