Inhaled PDE5's treat CF

Never realized the plan was to nebulize cialis or levitra - always thought we would just take them as a pill. So interesting....

Expert Opin Investig Drugs. 2011 Mar 24. [Epub ahead of print]

Inhaled phosphodiesterase type 5 inhibitors for cystic fibrosis: a new therapy for systemic disease?

Antoniu SA.

University of Medicine and Pharmacy "Gr.T.Popa" Iasi, Department of Internal Medicine II-Pulmonary Disease, Pulmonary Disease University Hospital, 30 Dr I Cihac Str, 700115 Iasi, Romania +40 232 

239408 ; +40 232 270918 ; sabina.antonela.antoniu@pneum.umfiasi.ro.

Abstract

Cystic fibrosis is a rare disease characterized by abnormalities in chloride and sodium transmembrane transportation due to various mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, F508del being the most commonly found. Corrective therapies for this defect are currently under investigation and PDE5 inhibitors such as sildenafil or vardenafil were found to improve CFTR activity in vitro as well as in vivo. This paper evaluates a study investigating the effects of inhaled PDE5 inhibitors in an animal model of F508del cystic fibrosis, demonstrating that in this new formulation, such compounds are also able to improve CFTR function. Such results support the further development of this therapy for a systemic disease such as cystic fibrosis, provided several issues are addressed.

PMID: 21434839 [PubMed - as supplied by publisher

Viagra / Cialis / Levitra and restoration of chloride channels in CF

Eur Respir J. 2010 Jun 18.

Inhaled PDE5 inhibitors restore chloride transport in cystic fibrosis mice.

Lubamba B, Lebacq J, Reychler G, Marbaix E, Wallemacq P, Lebecque P, Leal T.
Université Catholique de Louvain Ave Hippocrate 10, Brussels, Belgium.

Abstract

Sildenafil and vardenafil, two selective inhibitors of phosphodiesterase type 5 (PDE5) are able, when applied by intraperitoneal injection, to activate chloride transport in cystic fibrosis (CF) mice homozygous for the F508del mutation.

Oral treatment with the drugs may be associated with adverse hemodynamic effects. We hypothesized that inhaled PDE5 inhibitors are able to restore ion transport in F508del-CF airway epithelium. We developed a restraint-free mouse chamber for inhalation studies. PDE5 inhibitors were nebulized for 15 minutes at concentrations adjusted from recommended therapeutic oral doses for male erectile dysfunction.

We measured in vivo nasal transepithelial potential difference 1 hour after a single inhalation of sildenafil, vardenafil or tadalafil in F508del-CF and in normal homozygous mice. After nebulization with the drugs in F508del mice, chloride transport, evaluated by perfusing the nasal mucosa with chloride-free buffer containing amiloride followed by forskolin, was normalized; the forskolin response was increased with the largest values being observed with tadalafil and intermediate values with vardenafil.

No detectable effect was observed on sodium conductance. Our results confirm the role of PDE5 inhibitors for restoring chloride transport function of F508del-CFTR protein and highlight the potential of inhaled sildenafil, vardenafil and tadalafil as a therapy for CF.