Comparison of Pharmacokinetics of Vardenafil Administered Using an Ultrasonic Nebulizer for Inhalation vs a Single 10-mg Oral Tablet.
Delivery of vardenafil (for improvement of erectile function) via the inhaled route of administration may be advantageous in that this avoids extensive first pass metabolism and may therefore increase the bioavailability (hence the reliability of absorption) and shorten the time of pharmacological onset of activity. A unique nebulizer design has been developed by the sponsor (Advanced Medical Institute Pty Ltd) that is capable of delivering relatively large volumes of drug.



The primary objective of the Phase 1 study was to assess and compare the pharmacokinetics of a single dose of vardenafil 10-mg tablet and a single dose of vardenafil solution administered via inhalation using an ultrasonic nebulizer device. Secondary objective was to assess the safety of vardenafil administered via inhalation using an ultrasonic nebuliser device.



Two-part study in healthy volunteers. Dose-ranging study was performed in two subjects to determine the appropriate inhalational dose, followed by an open, randomized, crossover, single dose pharmacokinetic study in 12 subjects, which compared a single 10-mg oral dose to the inhalation dose.



Cmax, Cmax/Dose, Tmax, ke, t1/2, AUC0-t, AUCt-∞, AUC0-∞, AUC0-∞, AUC0-∞/Dose, and % area extrapolated.



The two treatments are not bioequivalent, with vardenafil absorbed and eliminated faster and with less variability using the nebulizer for drug delivery. Administration via the inhalational route was not associated with any clinically significant changes in blood pressure or heart rate, and no serious adverse events were recorded, demonstrating an acceptable safety profile.



To our knowledge, this is the first report of the administration of vardenafil HCl via the pulmonary route of administration. This trial demonstrates that vardenafil HCl may be administered using the ultrasonic nebulizer to reach blood levels comparable with those produced by a vardenafil 10-mg oral tablet, faster and using less drug. This new route of administration may potentially improve the onset of action, reliability, and safety for this class of drug.
Rochedale South, Queensland, Australia. Electronic address: berrygiess@optusnet.com.au.
Brooke
B
Berry
Altman Biomedical Consulting, Cammeray, New South Wales, Australia.
Phillip
P
Altman
NxGen Pharmaceuticals Pty Ltd, Taren Point, New South Wales, Australia.
James
J
Rowe
Advanced Medical Institute Pty Ltd, Sydney, New South Wales, Australia.
Jack
J
Vaisman
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D007172:Erectile Dysfunction / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D015203:Reproducibility of Results; D013607:Tablets; D014465:Ultrasonics; D000069058:Vardenafil Dihydrochloride / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
D013607:Tablets; D014665:Vasodilator Agents; D000069058:Vardenafil Dihydrochloride
Comparative; Inhalation; PDE5 Inhibitor; Pharmacokinetics; Vardenafil