A Phase I clinical trial of lodenafil carbonate, a new phosphodiesterase Type 5 (PDE5) inhibitor, in healthy male volunteers.
Lodenafil carbonate is a new phosphodiesterase Type 5 (PDE5) inhibitor used in treatment of erectile dysfunction.


OBJECTIVE
The present study was conducted to evaluate the safety, tolerability, and pharmacokinetics of lodenafil carbonate after administering ascending (1 - 100 mg) single oral doses to healthy male volunteers (n = 33).


METHODS
The study was an open label, dose-escalation, Phase I clinical trial involving the administration of single oral doses of lodenafil carbonate. Lodenafil carbonate was administered sequentially, escalating in single doses of 1 mg - 100 mg with a washout period of at least 1 week between each dose. The progression to the next dose was allowed after clinical and laboratory exams, Ambulatory Monitoring of Arterial Pressure (AMAP) without relevant clinical modifications and adverse events without clinical relevancy. Blood samples were collected at pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 h post-dosing. Plasma samples for measurement of lodenafil carbonate and lodenafil were analyzed by liquid chromatography coupled to tandem mass spectrometry.


RESULTS
No serious adverse events were observed, and none of the subjects discontinued the study due to intolerance. The AMAP measurements, clinical and laboratory exams and ECG revealed no significant changes even at higher doses. Lodenafil carbonate was not detected in any samples, indicating that it acts as a prodrug. The mean lodenafil pharmacokinetic parameters for tmax and t1/2 were 1.6 ( ± 0.4) h and 3.3 ( ± 1.1) h, respectively. This study demonstrated that lodenafil carbonate was well tolerated and showed a good safety profile in healthy male volunteers.
Department of Pharmcology, State University of Campinas, Campinas, Brazil. gugamendes@terra.com.br
Gustavo D
GD
Mendes
Hilton Oliveira
HO
dos Santos Filho
Alberto
A
dos Santos Pereira
Fabiana D
FD
Mendes
Jaime O
JO
Ilha
Khalid M
KM
Alkharfy
Gilberto
G
De Nucci
D000293:Adolescent; D000328:Adult; D018660:Blood Pressure Monitoring, Ambulatory; D002254:Carbonates / Q000009:adverse effects* / Q000493:pharmacokinetics; D004562:Electrocardiography / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000009:adverse effects*; D010879:Piperazines / Q000009:adverse effects* / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000009:adverse effects* / Q000493:pharmacokinetics
D002254:Carbonates; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011743:Pyrimidines; C532120:lodenafil carbonate