Cystic Fibrosis Patients Could Soon Take a Deep Breath of Ibuprofen

JULY 20, 2016
Meghan Ross, Senior Associate Editor
For patients with cystic fibrosis (CF), ibuprofen can help slow down lung function decline. The only problem is that consistent, high-dose ibuprofen use can lead to gastrointestinal bleeding, as well as kidney injury if taken with nephrotoxic intravenous antibiotics, which are commonly taken among CF patients.
 
The solution to this problem could be breathable ibuprofen. 
 
Carolyn L. Cannon, MD, PhD, associate professor of microbial pathogenesis and immunology at Texas A&M Health Science Center, is working in the preclinical phase of some nanoparticle formulations of this proposed therapy.
 
“We need to complete some pharmacokinetic (PK) studies in mice to demonstrate that we have attained our goal to achieve high concentrations of ibuprofen in the lungs and low systemic concentrations,” Dr. Cannon told Plantsvszombies.info. “We anticipate that we will be pleased with the results based on our experience with nanoparticle formulations of other compounds, but we need the data.”
 
The next step after that would be reproducing experiments that were done with oral ibuprofen. 
 
“We have shown that mice with pneumonia who received oral ibuprofen had fewer bacteria in the lungs and a better survival compared with mice who received a sham treatment,” Dr. Cannon explained. “We need to demonstrate that we achieve the same results or better with aerosolized ibuprofen nanoparticles.”
 
Once the researchers are able to prove this, Dr. Cannon thinks they can start speaking with the FDA. She said they are still years away from the product being approved, but it may be within a decade. 
 
Because Dr. Cannon is a pediatric pulmonologist, her interest has been developing the product to help the needs of her patients with CF, but she would also be pleased if inhaled nanoparticle ibuprofen could eventually be turned into an OTC product. 
 
“If this potential product serves to help other patient populations, I would be thrilled!” she said. 
 
The idea for developing inhaled ibuprofen originally came from Michael Konstan, MD, the pediatric department chair at Case Western University School of Medicine, who showed that patients with CF who received oral, high-dose ibuprofen (20 mg/kg, or 6 of the 200-mg tablets for a 60-kg person) were able to retain lung function and needed fewer courses of antibiotics. He also found that rats who took high-dose ibuprofen slowed the influx of the neutrophil into the lung, which provided an anti-inflammatory effect. 
 
Dr. Cannon explained that Dr. Konstan’s Cystic Fibrosis Care Center at Rainbow Babies and Children’s Hospital still provides high-dose ibuprofen as a treatment option, but few other places do so because of potential adverse effects.
 
“One large bleed in a center and physicians, who have pledged to ‘first, do not harm’ abandon the treatment for all of their patients,” she explained. “One episode of acute kidney injury in a CF center and the ibuprofen treatment is similarly abandoned. So, nobody uses a highly effective treatment due to fear of side effects. Let’s eliminate the side effects!” 
 
Their idea is to use inhaled ibuprofen to ideally allow for a high, local concentration in the lung, with low systemic concentration, which will eliminate the risk of kidney injury. However, they still need to prove that this is possible. 
 
“The fact that ibuprofen, at these concentrations, acts as an antimicrobial itself and synergizes with other antimicrobials, is an unexpected bonus, and likely further explains why the CF patients on high-dose ibuprofen did so well in Dr. Konstan’s studies,” Dr. Cannon said.
 
Like teaching an old dog new tricks, Dr. Konstan and Dr. Cannon are hoping the different CF patients in the not-so-distant future.
 


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