Inhaled Revatio (sildenafil) appears to be superior to current oral forms of this approved pulmonary arterial hypertension (PAH) treatment by allowing for lower doses and potentially fewer systematic side effects, researchers report. They also recommend that a nebulized form of Revatio be produced and moved into clinical testing in patients.
The study reporting this finding, “Inhaled Sildenafil As An Alternative To Oral Sildenafil In The Treatment Of Pulmonary Arterial Hypertension (PAH),” was pubished in the Journal of Controlled Release.
Revatio acts by dilating blood vessels and reducing blood pressure, leading to improved exercise capacity and slower disease progression in PAH patients. However, its use (oral tablets or intravenous) is associated with issues that include a large dose, short dosing intervals, and unwanted system-wide side effects. It is currently approved only for adults, and is not recommended for pediatric patients.
“We believe that many of the limitations of oral sildenafil can be overcome by reducing the dose and dosing frequency of the drug,” the researchers wrote. “In fact, as an alternative to the oral form of the drug, … [nebulized] particles of sildenafil have been prepared with a goal to treat PAH and other diseases.”
Nebulized formulations, which allow for prolonged release of an inhaled drug, have been tested for Revatio, but no studies have compared the effects of a nebulized and oral form of this drug.
Researchers prepared a formulation of inhaled Revatio and evaluated its effectiveness by assessing characteristics like drug release and absorption rate, interaction with alveolar macrophages (immune system’s cells), and safety after aerosolization into the lungs.
They then tested the new formulation in healthy rats, and tested its effects on pulmonary arterial pressure in rats with PAH.
Results showed that the nebulized Revatio had a favorable absorption in the lungs, underwent slower macrophage uptake, was released for an extended period (36 hours), and was maintained in the lungs for a longer period than the oral form without being eliminated by the body. The drug also lowered the pulmonary arterial pressure in rats for six hours.
“[P]reparing and characterizing [inhaled] sildenafil, monitoring [its action] in healthy rats, assessing the pharmacological efficacy in PAH rats, we have demonstrated that an inhaled long-acting formulation of sildenafil can potentially be developed as a viable alternative to oral tablets of sildenafil — the current dosage form, which prompts patients to noncompliance because of multiple dosing a day,” the researchers wrote.
“Because both the drug and [the particles that carry the inhaled drug] are already FDA approved for human use, this alternative delivery system for sildenafil would be cost-effective to rapidly test and develop as a viable anti-PAH formulation,” the team added.