Clinical update on phosphodiesterase type-5 inhibitors for erectile dysfunction

Erectile dysfunction (ED) affects the sexual lives of millions of men. The first-line oral pharmacotherapy for most ED patients is phosphodiesterase type-5 (PDE-5) inhibitors, of which three are available. Sildenafil is the most widely prescribed oral agent for ED and has a very satisfactory efficacy–safety profile in all patient categories. Tadalafil and vardenafil were introduced in the European Union and in the United States in 2003 and 2004, respectively. The three PDE-5 inhibitors share many pharmacological and clinical characteristics, and each has unique features. This review, which is based on the contemporary literature on PDE-5 inhibitors, describes the chemical, pharmacological, and clinical features of sildenafil, vardenafil, and tadalafil. The first section reviews the pathophysiology of penile erection and PDE-5 inhibitor pharmacology. The second section summarizes data regarding efficacy and safety of the three drugs in treating ED in the general population as well as in selected patient categories.     

Duplex ultrasound evaluation of cavernosal peak systolic velocity and waveform acceleration in the penile flaccid state: clinical significance in the assessment of the arterial supply in patients with erectile dysfunction

The aim of this paper was to establish if duplex ultrasound parameters obtained for assessment of the patency of cavernosal arteries in the penile flaccid state can give sufficient clinical information without the use of intracavernosal injection of vasodilatory drugs. We assessed mean cavernosal peak systolic velocity (PSV) in the penile flaccid state (basal PSV), and after PGE1 injection (dynamic PSV) in 339 unselected patients with erectile dysfunction. In 55 of these patients the waveform acceleration in the flaccid state was also assessed. The results of the study can be summarized as follows: (1) a significant relationship was found between basal and dynamic PSV in the 339 patients (r=0.477; p < 0.0001); (2) a basal PSV >12.5 cm/sec was predictive of a dynamic PSV >/=30 cm/sec in 129/139 (92.8%) of the patients, whereas in patients with a basal PSV or <30 cm/sec could be found; and (3) an acceleration >1 m/sec2 in the flaccid state was coupled to a dynamic PSV >30 cm/sec in 43/46 (93.5%) of the patients independent of the basal PSV. In conclusion, these results suggest that the combined duplex ultrasound assessment of PSV and waveform acceleration in the penile flaccid state can predict arterial dynamic inflow in the majority (51/55; 92.7%) of patients with erectile dysfunction, with less time and expense and less discomfort for the patient.     

Spontaneous regression of initially elevated peak systolic velocity in renal transplant artery

There is limited knowledge about the incidence, clinical implication and spontaneous course of transplant renal artery stenosis detected early after renal transplantation. We performed Doppler ultrasound examination of the transplant artery(s) 2 months after transplantation in 98 consecutive patients and peak systolic velocity (PSV) was measured. All patients with an elevated PSV ≥1.8 m/s were reexamined 20 months later and clinical data were followed for 3 years. At the initial examination 2 months after transplantation 15 recipients had a PSV ≥1.8 m/s, mean value for PSV 2.5 (1.8–3.6) m/s, whereas 83 recipients had a normal PSV of 1.3 (0.7–1.7) m/s (P < 0.01). At baseline there were no statistical significant differences in clinical parameters between the high PSV versus normal PSV recipients. Twenty (15–28) months after transplantation 14 patients with initial elevated PSV were re‐examined. There was an overall mean reduction in PSV of 0.5 (?0.7 to 1.2) m/s from 2.4 (1.8–3.4) m/s to 1.9 (1.2–3.1) m/s (P = 0.02). Detection of a high PSV early after transplantation did not affect graft function or blood pressure 3 years after engraftment. We conclude that a high PSV, at 2 months after engraftment, seems to be more of an ‘incidental finding’ that should be re‐challenged and carefully interpreted.     

Erectile potentials of a new phosphodiesterase type 5 inhibitor, DA-8159, in diet-induced obese rats

Aim： To examine the changes in the erectile function in diet-induced obese rats and investigate the oral efficacy of DA-8159, a new phosphodiesterase type 5 （PDE5） inhibitor, on penile erection in obese rats. Methods： The rats were fed a high-energy diet for 12 weeks and divided into three groups： an obesity-resistant （OR） control group, an obesity-prone （OP） control group, and an OP-DA-8159 treatment （DA-8159） group. The electrostimulation-induced erectile responses were measured in all groups. The body weight, plasma cholesterol, triglyceride and glucose levels were also measured. Results： In the OP control group, the maximum intracavernous pressure （ICP） and ICP/blood pressure （ICP/BP） ratio after electric stimulation were significantly lower than those in OR control group. The corresponding area under the curve （AUC） of the ICP/BP ratio, the detumescence time and the baseline cavernous pressure were also lower than those in the OR control group, but this difference was not significant. The body weight gain, plasma cholesterol and triglyceride level in the OP group were significantly higher than those in the OR group. After administering the DA-8159, a significant increase in the maximum ICP and the ICP/BP ratio were observed. The corresponding AUCs in the DA-8159 group were also higher than those in the two control groups. Furthermore, the detumescence time was significantly prolonged after treatment with DA-8159. Conclusion： These results demon- strate that diet-induced obesity affects the erectile function in rats and these erectile dysfunction （ED） can be improved by the treatment with DA-8159, indicating DA-8159 might be a treatment option for ED associated with obesity.     

一种新型磷酸二酯酶5抑制剂DA-8159对食源性肥胖大鼠的勃起促进作用

目的:调查食源性肥胖大鼠的勃起功能的变化,评价口服新型磷酸二酯酶5(PDE5)抑制剂 DA-8159对其阴茎勃起的作用。方法:实验大鼠用高热量食物喂养12周后分为三组:不易肥胖对照组(OR),易肥胖对照组(OP)和接受 DA-8159处理的 OP 组(DA-8159)。用电刺激法引发3个实验组大鼠的勃起并测量其勃起反应。同时测量实验大鼠的体重、血胆固醇、甘油三酯和葡萄糖水平。结果:OP 对照组大鼠电刺激后的最大海绵体内压(ICP)和 ICP 与血压比(ICP/BP)都显著地比 OR 对照组低,ICP/BP曲线下面积(AUC)的相应区域、勃起消退时间、海绵体基线压也低于 OR 对照组,但无显著差异;体重、血浆胆固醇、甘油三酸酯水平显著高于 OR 组。口服 DA-8159后,实验大鼠的最大 ICP 和 ICP/BP 值都显著提高。DA-8159处理组的相应 AUC 也高于对照组,而且 DA-8159处理后,大鼠的勃起消退时间也显著延长。结论:本研究结果表明食源性肥胖会影响大鼠的勃起功能,口服 DA-8159会改善其勃起功能障碍(ED),所以 DA-8159可能将成为治疗肥胖导致的 ED 的一种待选药物。     

Direct effects of selective type 5 phosphodiesterase inhibitors alone or with other vasodilators on the erectile response in cats

PURPOSE: Zaprinast, dipyridamole and sildenafil were injected into the corpora cavernosa of cats to determine whether changes in the steady state level of cyclic guanosine monophosphate (cGMP) induced by inhibiting type 5 phosphodiesterase would cause an erectile response. MATERIALS AND METHODS: Increases in intracavernous pressure, penile length and erectile response duration were determined after intracavernous injection of the type 5 cGMP specific phosphodiesterase inhibitors zaprinast, dipyridamole and sildenafil as well as combined zaprinast and prostaglandin E1 (PGE1), and zaprinast and sodium nitroprusside. Systemic arterial pressure was concurrently assessed in these experiments. All responses to phosphodiesterase inhibitors were compared to a control triple drug combination of 1.65 mg papaverine, 0.5 microg PGE1 and 25 microg phentolamine. RESULTS: Each selective type 5 phosphodiesterase inhibitor caused dose related increases in intracorporeal pressure and penile length. However, none of the compounds was as effective as the control drug combination of papaverine, phentolamine and PGE1. Combining zaprinast with sodium nitroprusside led to further increases in pressure and erectile response duration that more closely resembled the control drug response. Combining zaprinast with PGE1 led to a response that was indistinguishable from the control response. CONCLUSIONS: The results of these feline studies establish that administering a type 5 phosphodiesterase inhibitor without concomitant administration of a nitric oxide donor or stimulation of the cavernous nerves may have a direct effect on the erectile response. These data also suggest that combining a selective type 5 phosphodiesterase inhibitor with PGE1 may be highly effective local therapy for erectile dysfunction and an acceptable alternative to other current forms of treatment.     

Penile erectile responses to electric stimulation are enhanced by a new phosphodiesterase type-5 inhibitor

AIM: This study was conducted to investigate the effect of DA-8159, a new phosphodiesterase type-5 (PDE5) inhibitor, on electrostimulation-induced penile erection in rats. METHODS: Intracavernous pressure (ICP) and arterial blood pressure (BP) were simultaneously recorded through electric pelvic-ganglion stimulation (2-10 Hz) after the oral administration of DA-8159 (3 or 10 mg/kg) in normal and streptozotocin-induced diabetic rats. Statistical analysis was performed on the maximal intracavernous pressure (ICP), detumescence time, maximal intracavernous pressure/blood pressure (ICP/BP) ratio, and the area under the curve (AUC) of the ICP/BP ratio. RESULTS: In normal and diabetic rats, electrical stimulation of the pelvic ganglion induced a frequency- and dose-dependent increase in the intracavernous pressure. The ICP/BP ratio and the corresponding AUC values were also significantly and dose-dependently increased after DA-8159 administration. In addition, the detumescence time significantly increased after DA-8159 administration compared to that of the controls. CONCLUSIONS: These results show that the DA-8159 significantly increased the intracavernous pressure response and prolonged the decay period induced by electrical stimulation of the pelvic ganglion, and suggest that DA-8159 might be a potential therapeutic agent for the treatment of erectile dysfunction.     

Efficacy of type-5 phosphodiesterase inhibitors in the drug treatment of premature ejaculation: a systematic review

This review examines the role of nitric oxide (NO) as a neurotransmitter involved in the central and peripheral control of ejaculation, the methods of phosphodiesterase type 5 inhibitor (PDE5I) drug treatment studies for premature ejaculation (PE), the adherence of methods to the contemporary consensus of ideal PE drug trial design, the impact of methods on treatment outcomes and the role of PDE5Is in the treatment of PE. NO/cGMP transduction is involved in both the central and peripheral control of emission, but evidence for a direct central or peripheral effect of PDE5Is on ejaculation is speculative. Thirteen of the 14 studies reviewed failed to fulfil the evidence-based medicine criteria for ideal PE drug trial design. Limitations of the studies include inadequately defined study populations, the lack of a double-blind placebo-controlled study design, and the absence of consistent objective physiological measures or sensitive, validated outcome assessment instruments as study endpoints. The broad range of intravaginal ejaculatory latency time (IELT) fold-increases reported with PDE5Is, on-demand selective serotonin re-uptake inhibitor (SSRI) drugs, and combined PDE5I/on-demand SSRIs is testament to the unreliability of data and conclusions from methodologically flawed studies. The one study that fulfilled the evidence-based medicine criteria of an ideal clinical trial design reported that treatment with sildenafil failed to significantly increase baseline IELT, supporting our conclusion that there is no convincing evidence to support any role for PDE5Is in the treatment of men with lifelong PE and normal erectile function. However, there is limited evidence to support a potential role for PDE5Is alone or combined with daily or on-demand SSRIs in the treatment of acquired PE in men with comorbid erectile dysfunction. Further controlled studies adhering to the contemporary consensus of ideal clinical trial design are required to clarify the role of PDE5Is in this subgroup of men with acquired PE.     

Effects of respiration on the velocity of tricuspid regurgitation and estimation of systolic pulmonary artery pressure in patients with right ventricle systolic dysfunction

Objective. We investigated the effects of quiet respiration on the peak velocity of tricuspid regurgitation (TR) and estimation of systolic pulmonary artery pressure (SPAP) in patients with right ventricle (RV) systolic dysfunction using Doppler echocardiography. Methods. Continuous-wave Doppler spectra of TR were recorded in 32 patients with and 28 controls without RV systolic dysfunction. Electrocardiography and respiratory tracing were recorded simultaneously. Expiratory and inspiratory peak velocities of TR were acquired and averaged for five consecutive respiratory cycles. The SPAP during expiration and inspiration was calculated. Results. The velocity of TR and SPAP was not significantly different between expiration and inspiration in controls (2.77 ± 0.23 and 2.82 ± 0.26 m/s, P = 0.776; 35.94 ± 4.96 and 36.18 ± 5.12 mmHg, P = 0.747), whereas the velocity of TR and SPAP decreased significantly from expiration to inspiration in patients with RV systolic dysfunction (3.27 ± 0.35 and 2.59 ± 0.22 m/s, P < 0.001; 53.72 ± 7.39, 38.45 ± 5.63 mmHg, P < 0.001). Conclusions. Quiet respiration has significant effects on the velocity of TR in patients with RV systolic dysfunction. This factor should be taken into account when using Doppler echocardiography to estimate these patients’ SPAP, and the measurements should be performed in patients at the end of expiration.     

Efficacy and safety of phosphodiesterase type 5 (PDE5) inhibitors in treating erectile dysfunction after bilateral nerve‐sparing radical prostatectomy

We carried out a systematic review and meta‐analysis to assess the efficacy and safety of phosphodiesterase type 5 (PDE5) inhibitors for treating erectile dysfunction (ED) after bilateral nerve‐sparing radical prostatectomy (BNSRP). A literature review was performed to identify all published randomised double‐blind, placebo‐controlled trials of PDE5 inhibitors for the treatment of ED after BNSRP. The search included the following databases: MEDLINE, EMBASE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Six publications involving a total of 1678 patients were used in the analysis, including six RCTs that compared PDE5 inhibitors (tadalafil, sildenafil, avanafil and vardenafil) with placebo. Co‐primary efficacy end points: International Index of Erectile Function‐Erectile Function (IIEF‐EF) domain score [the standardised mean difference (SMD) = 4.04, 95% confidence interval (CI) = 2.87–5.22, P < 0.00001]; successful vaginal penetration (SEP2) [the odds ratio (OR) = 14.87, 95%CI = 4.57–48.37, P < 0.00001]; and successful intercourse (SEP3) (OR = 47, 95%CI = 3–13.98, P < 0.00001) indicated that PDE5 inhibitors was more effective than the placebo. Specific adverse events with PDE5 inhibitors included headache (12.08%), dyspepsia (6.76%) and flushing (6.52%), which were significantly less likely to occur with placebo. This meta‐analysis indicates that PDE5 inhibitors to be an effective and well‐tolerated treatment for ED after BNSRP.     

Evaluation and diagnostic testing of erectile dysfunction in the era of phosphodiesterase type 5 inhibitors

The diagnosis and treatment of erectile dysfunction has changed dramatically since the availability of safe and effective oral therapies. Unfortunately, not all men can be adequately treated in this way, and might require more invasive testing to diagnose and treat the specific cause of their dysfunction. This review looks at the tests and strategies available for men who cannot be treated by oral therapy alone.     

Study of the prevalence and patterns of phosphodiesterase type 5 inhibitor use among sexually active Egyptian males: A National Cross‐sectional Survey

A cross‐sectional survey was conducted in Egypt from November 2015 to June 2016. Sexually active adult men were interviewed by a questionnaire designed by the authors. All the participants were evaluated by the abridged 5‐item version of the International Index of Erectile Function (IIEF). A total of 3,000 sexually active Egyptian males participated in this study, 946 (31.53%) reported using PDE5Is at least once, and 2054 (68.47%) have never used them. The majority of those who used PDE5Is obtained them for recreational purposes mainly for pleasure (58.35%) and to increase duration/frequency of the intercourse (15.6%). Only 26.05% used PDE5Is to treat ED. The main source of obtaining PDE5Is was friends, relatives and colleagues (62.79%); 25.16% of users obtained the drug by themselves, and 6.66% were prescribed the drug by a pharmacist. Only 5.39% of users obtained the drug after a specialist physician consultation. Sildenafil was the most commonly used PDE5I (90.6%), and most of the users (88.05%) used them in an occasional manner even in the presence of erectile dysfunction, while 11.95% used the drug in a regular manner for every intercourse. PDE5Is are frequently used by the Egyptian male population, and most of them seemed to take them as recreational medications.     

Penile rehabilitation protocol after robot‐assisted radical prostatectomy: assessment of compliance with phosphodiesterase type 5 inhibitor therapy and effect on early potency

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To evaluate factors that affect compliance in men who enrol in a phosphodiesterase type 5 inhibitor (PDE5I) protocol after nerve‐sparing robot‐assisted prostatectomy (RAP), and report on short‐term outcomes, as PDE5Is may help restore erectile function after RAP and patient adherence to the regimen is a factor that potentially can affect outcome.

PATIENT AND METHODS

We prospectively followed 77 men who had nerve‐sparing RAP and enrolled in a postoperative penile rehabilitation protocol. The men received either sildenafil citrate or tadalafil three times weekly. The minimum follow‐up was 8 weeks. Potency was defined as erection adequate for penetration and complete intercourse. Compliance was defined as men adhering to the regimen for ≥2 months.

RESULTS

The mean age of the cohort was 57.8 years and the median follow‐up was 8 months. In all, 32% of the men discontinued the therapy <2 months after RAP and were deemed noncompliant with an additional 39% discontinuing therapy by 6 months, with the high cost of medication being the primary reason (65%). Long‐term compliance and preoperative erectile dysfunction were independent predictors of potency return after adjusting for age and nerve sparing.

CONCLUSIONS

The high cost of medication remains a significant barrier to maintaining therapy. Noncompliance to PDE5I therapy in a tertiary care centre was much higher than reported in clinical trial settings. With longer‐term follow‐up, we need to further define the factors that improve overall recovery of sexual function after RAP.     

The effects of phosphodiesterase type 5 inhibitors on penile rigidity variables during a period with no sexual stimulation: a laboratory setting double‐blind study

Study Type – Therapy (RCT)
Level of Evidence 1b What’s known on the subject? and What does the study add? There is a positive effect of PDE5 inhibitors on several aspects of the men’s sex lives, chiefly erectile function, personal self‐esteem, and satisfaction from their sex lives. To our knowledge, our study is the first study to evaluate the effects of PDE5 inhibitors on erectile variables simultaneously in a laboratory setting. In the present study, significant penile rigidities were obtained with PDE5 inhibitors in a short period, with no sexual stimulation, in laboratory conditions. Our findings might support the use of PDE5 inhibitors in the men who need penile rehabilitation.

OBJECTIVE

To investigate the effects of phosphodiesterase type 5 (PDE5) inhibitors on erectile variables during a period with no sexual stimulation in a laboratory setting double‐blind study.

PATIENTS AND METHODS

In all, 80 men without erectile dysfunction (ED) but with lifelong premature ejaculation (PE) were included in the study. The men were divided equally in to four groups and received either placebo, vardenafil (10 mg), sildenafil (50 mg) or tadalafil (20 mg) in a double‐blind study design. The men attended the laboratory following 3 days of sexual abstinence and placebo or one of the PDE5 inhibitors was ingested after ≥2 h of fasting and non‐smoking. The men were then immediately placed in a silent room and real‐time penile rigidity and tumescence monitoring with Rigiscan Plus (Rigiscan Plus® System, Osbon Medical Systems, Augusta, GA, USA) began. The men read some magazines or newspapers that contained no sexually stimulating material for 1.5 h. There was no interaction between the men and observer during the test period. Times to first measured and total durations of base and tip rigidities, and also total and per minute rigidity were evaluated.

RESULTS

The recorded base and/or tip rigidity ratios were 40% (eight of 20), 71% (12/17), 47% (nine of 19) and 70% (14/20) in men who took placebo, sildenafil, tadalafil and vardenafil, respectively (P= 0.126). The ratio of men who could obtain ≥60% base and/or tip rigidities were 10% (two of 20), 41% (seven of 17), 26% (five of 19) and 55% (11/20) in placebo, sildenafil, tadalafil and vardenafil groups, respectively (P < 0.05). The median time to first measured base rigidity was 58.0, 21.5, 54.5 and 57 min with placebo, sildenafil, tadalafil and vardenafil, respectively (P= 0032). The median total duration of recorded base rigidity was 4.0, 27.5, 10.0 and 11.5 min in men who took placebo, sildenafil, tadalafil and vardenafil, respectively (P= 0.013). The median total base rigidity (area under the curve) was 72.8, 699.0, 360.5 and 553.0 with placebo, sildenafil, tadalafil and vardenafil, respectively (P= 0.016).

CONCLUSIONS

Significant penile rigidities were obtained with PDE5 inhibitors during the short test period, with no sexual stimulation, in laboratory conditions. This finding might support the use of PDE5 inhibitors in men who need penile rehabilitation.     

Incidence rate of prostate cancer in men treated for erectile dysfunction with phosphodiesterase type 5 inhibitors: retrospective analysis

The purpose of this study was to determine the incidence rate of prostate cancer among men with erectile dysfunction (ED) treated with phosphodiesterase type 5 inhibitors (PDE-5i) over a 7-year period vs. men with ED of the same age and with similar risk factors who were not treated with PDE-5i. In a retrospective review of electronic medical records and billing databases between the years 2000 and 2006, men with ED between the ages of 50 and 69 years and no history of prostate cancer prior to 2000 were identified. These individuals were divided into two groups: 2362 men who had treatment with PDE-5i, and 2612 men who did not have treatment. Demographic data in each group were compared. During the study period, 97 (4.1%) men with ED treated with PDE-5i were diagnosed with prostate cancer compared with 258 (9.9%) men with ED in the non-treated group (P<00001). A higher percentage of African Americans were treated with PDE-5i vs. those who were not (10.5% vs. 7.1% P<0.0001). The PDE-5i group had lower documented diagnosis of elevated prostate-specific antigen (10.0% vs. 13.1% P=0.0008) and higher percentage of benign prostatic hyperplasia (38.4% vs. 35.1% P=0.0149). Men with ED treated with PDE-5i tended to have less chance (adjusted odds ratio: 0.4; 95% confidence intervals: 0.3–0.5; P<0.0001) of having prostate cancer. Our data suggest that men with ED treated with PDE-5i tended to have less of a chance of being diagnosed with prostate cancer. Further research is warranted.     

Testosterone undecanoate improves erectile dysfunction in hypogonadal men with the metabolic syndrome refractory to treatment with phosphodiesterase type 5 inhibitors alone

At least 30–35% of men with erectile dysfunction (ED) fail to respond to treatment with phosphodiesterase type 5 (PDE‐5) inhibitors. Testosterone (T) has effects not only on sexual desire, but also on the anatomical and physiological substrate of erection. This study analysed the effects of T administration to men unsuccessfully treated for ED with PDE‐5 inhibitors only. Twenty‐nine men aged 36–75 years (mean 59 years) with ED were studied. They suffered from ED for a mean of 2.7 years and had subnormal plasma T levels (total T <3.5 ng ml^?1). They received parenteral testosterone undecanoate for 102 weeks. Changes of the domains of the International Index of Erectile Function (IIEF) were assessed. After 6 weeks of T treatment, the sexual desire domain of IIEF had improved (from 4.1 ± 1.4 to 7.2 ± 1.7) and erectile function as measured by IIEF started to improve, reaching a plateau after 30 weeks (from 9.1 ± 2.1 to 26.5 ± 2.3). Features of the metabolic syndrome also improved. There were no adverse effects of T administration. Addition of T to treatment of hypogonadal men unsuccessfully treated with PDE‐5 inhibitors only, appeared useful and acceptably safe.     

Activity of phosphodiesterase type 5 inhibitors in patients with lower urinary tract symptoms due to benign prostatic hyperplasia

Study Type – Therapy (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? Phosphodiesterase type 5 inhibitors (PDE 5Is) improve erectile function and lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH), however the exact effects on prostate tissue and its underlying mechanisms remain unclear. PDE 5Is enhanced the production of cyclic nucleotides in the plasma and prostate, and the distribution of PDE 5Is in the prostate was higher than in the plasma.

OBJECTIVE

? To evaluate the impact and distribution of a single phosphodiesterase type 5 inhibitor (PDE5 I) dose (udenafil or tadalafil) in prostate tissue and plasma in patients with benign prostatic hyperplasia (BPH).

PATIENTS AND METHODS

? Thirty BPH patients complaining of erectile dysfunction along with moderate‐to‐severe lower urinary tract symptoms (LUTS) who underwent transurethral resection of the prostate (TURP) were enrolled in the present study. ? The patients were randomly divided into the three groups: group 1, TURP without PDE5 Is; group 2, 200 mg of udenafil given 1 h before TURP; and group 3, 20 mg of tadalafil given 1 h before TURP. ? We evaluated the concentrations of PDE5‐I, cAMP and cGMP in prostate tissues and plasma, and calculated the prostate tissue‐to‐plasma (T/P) ratio.

RESULTS

? The concentration of udenafil in prostate tissue and plasma was 2028.6 ± 360.8 ng/g and 463.7 ± 39.1 ng/mL, respectively, and the resulting T/P ratio was 4.4. The tadalafil concentration in prostate tissue and plasma was 385.7 ± 83.8 ng/g and 305.8 ± 41.1 ng/mL, respectively, and the T/P ratio was 1.3. ? Udenafil and tadalafil significantly increased the cAMP and cGMP levels in plasma and prostate tissues.

CONCLUSIONS

? Udenafil and tadalafil significantly increased cAMP and cGMP levels and were more highly distributed in the prostate than plasma. The T/P ratio of udenafil was higher than tadalafil. ? These findings may help in the assessment of the feasibility of using PDE5 Is to concurrently treat both LUTS and erectile dysfunction.