Pharmacological characterization of the novel phosphodiesterase type 5 (PDE5) inhibitor lodenafil carbonate on human and rabbit corpus cavernosum

Methods In functional studies, cavernosal strips were mounted in organ baths for isometric force recording, coupled to a PowerLab 8/SPTM data acquisition system. Rats were surgically manipulated and telemetry transmitters were implanted in the abdominal aorta for measurements of systolic, diastolic and mean arterial blood pressure. For determination of PDE activity by LC-MS/MS analysis, lodenafilc arbonate (0.005–1 μM) was preincubated in the enzymatic mixture for 5 min at room temperature. Reaction was initiated by the addition of the substrate cGMP (5 μM) at 35°C for 30 min. Pharmacokinetics was studied by tandem mass spectrometry (LC-MS/MS) with positive ion electrospray ionization using multiple reactions monitoring (NMR) method. Blood samples were collected at 0.02 to 24 h after drug administration by intravenous (1 mg/kg) and oral (10 mg) routes. The hydrolysis of lodenafil carbonate (final concentration 10 μM) was also studied in human, dog and rat plasma as well as in acid solution (100 mM hydrochloric acid).