490 3 Over the last decade numerous studies have
Over the last decade, numerous studies have evaluated the acute, short-term, and medium-term impact of pulmonary vasodilators on Fontan physiology.23., 24., 25., 26., 27., 28., 29., 30., 31. Although different 490 3 of medications have been evaluated, phosphodiesterase-5 (PDE-5) inhibitors have the longest track record of use in pediatrics and have an excellent safety profile. PDE-5 inhibitors have been used for more than a decade as the first-line therapy for children with pulmonary arterial hypertension and have been associated with increased exercise performance as well as increased measures of quality of life in that group.32., 33., 34., 35.
In children with Fontan physiology, there have been a number of acute and short-term efficacy studies of PDE-5 inhibitors; some have suggested an improvement in exercise performance, and others have been equivocal.24., 25., 27., 36. In the earliest publication, sildenafil was shown to improve exercise capacity and cardiac output after a single dose. In the largest and longest evaluation of sildenafil (6 weeks of therapy, 28 subjects), the authors found an improvement in submaximal exercise in those with heart failure (defined as a serum brain-type natriuretic peptide [BNP] >100 pg/mL) but no improvement in VO2 max. Interestingly, the authors also found an improvement in ventricular performance as quantified by the myocardial performance index.26., 27.
Study design and methods
Introduction An optimal outcome in the treatment of erectile dysfunction (ED) is to enable a return to normal erectile function (EF) . To achieve this goal, the method of administration and dosage of oral phosphodiesterase-5 inhibitors (PDE-5Is) have been expanded to once-daily repeated administration with lower dosage than that required for on-demand administration 2, 3, 4. Several clinical trials on once-daily administration of PDE-5I demonstrated an improvement in ED 2, 5, 6. Udenafil (Zydena®; Dong-A, Seoul, Korea), a recently developed selective PDE-5I, showed promising pharmacokinetic characteristics for use in a once-daily strategy with a peak plasma concentration at 0.8–1.3 hours, which then declines monoexponentially with a half-life (T1/2) ranging from 9.9 to 12.1 hours 7, 8, 9. During regular repeated administration, udenafil reaches steady state by day 5, without significant drug accumulation . We previously reported the outcomes of a placebo-controlled, randomized controlled trial on once-daily dosing of udenafil 25 mg, 50 mg, and 75 mg for 12 weeks. In that study, we demonstrated improved EF with safety with administration of udenafil at a dose of 50 mg or 75 mg once daily, in comparison with placebo . Based on these prior findings, we now focused on and evaluated the efficacy and safety of two different doses of udenafil (50 mg and 75 mg) once per day for a longer term period of 24 weeks as a treatment for ED, particularly from the viewpoint of assessing the recovery of normal EF by use of a patient-reported questionnaire in comparison with a placebo.
Materials and Methods
Subjects The same protocol used in our previous study was used for exclusion criteria : penile anatomic defects; spinal cord injury; prior radical prostatectomy or radical pelvic surgery; hyperprolactinemia; low level of total testosterone; poorly controlled diabetes (glycosylated hemoglobin >12%) or proliferative diabetic retinopathy; major uncontrolled psychiatric disorder; history of active peptic ulcer disease within 1 year of screening; history of major hematologic, renal or hepatic abnormalities; recent (within the previous 6 months) history of cardiovascular disease, stroke, myocardial infarction, cardiac failure, unstable angina, or a life-threatening arrhythmia; or history of alcoholism or substance abuse. Also excluded were persons taking androgens (e.g., testosterone) or anti-androgens. Prior use of other PDE-5Is was allowed; however, patients who reported not responding to other PDE-5Is were excluded from this study.