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Safety, Tolerability, and Pharmacokinetics of RT234 (Vardenafil Inhalation Powder): A First-in-Human, Ascending Single- and Multiple-Dose Study in Healthy Subjects
- Source :
- Journal of Aerosol Medicine and Pulmonary Drug Delivery
- Publication Year :
- 2021
- Publisher :
- Mary Ann Liebert, Inc., publishers, 2021.
-
Abstract
- Background: RT234 (vardenafil inhalation powder) is being developed for pulmonary administration “as needed”, to acutely improve exercise tolerance and symptoms in patients with pulmonary arterial hypertension (PAH). Methods: This single-center, open-label, randomized study in 32 healthy adult subjects evaluated single and multiple inhalation doses of RT234, for safety, tolerability, and pharmacokinetics (PKs). Results: RT234 was generally safe and well tolerated at single doses of 0.2–2.4 mg and after repeated dose administration of up to 2.4 mg q4h for four doses daily for 9 days. The most common treatment-emergent adverse events were mild-to-moderate headaches. There was no evidence of pulmonary irritation or inflammation. Vardenafil was absorbed very rapidly after inhalation as RT234, independent of dose level and number of doses administered. The tmax occurred at the time that the first blood sample following completion of dosing. After Cmax was achieved, plasma vardenafil concentrations declined rapidly in an exponential fashion that appeared to be parallel among dose levels. Vardenafil plasma concentrations and PK parameters increased in a dose-proportional manner. Vardenafil systemic exposure was notably greater after oral administration of 20 mg vardenafil tablets (Levitra®) than after administration of any dose level of RT234. During repeated dose administration of RT234, Cmax was attained rapidly following each dose and in a pattern similar to that observed after single-dose administration. Minor accumulation, characterized by very low mean morning predose vardenafil concentrations (
- Subjects :
- Pulmonary and Respiratory Medicine
Adult
Pharmaceutical Science
Administration, Oral
Multiple dose
030226 pharmacology & pharmacy
03 medical and health sciences
0302 clinical medicine
Pharmacokinetics
Double-Blind Method
Vardenafil Dihydrochloride
pulmonary arterial hypertension
Administration, Inhalation
medicine
Humans
Pharmacology (medical)
vardenafil
Original Research
inhalation
Inhalation
Dose-Response Relationship, Drug
business.industry
Healthy subjects
Safety tolerability
First in human
Healthy Volunteers
Inhalation powder
030228 respiratory system
Vardenafil
Anesthesia
Area Under Curve
Powders
business
pharmacokinetics
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 19412703 and 19412711
- Volume :
- 34
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Journal of Aerosol Medicine and Pulmonary Drug Delivery
- Accession number :
- edsair.doi.dedup.....140bcfdfd938a9da577d6e031946c9b4