Tadalafil Research Articles

Antidepressant-like effect of tadalafil, a phosphodiesterase type 5 inhibitor, in the forced swim test: Dose and duration of treatment dependence

Nitric oxide (NO), an intercellular messenger in central nervous system, plays an important role in the pathogenesis of major depression. Antidepressant-like effect of sildenafil, a phosphodiesterase 5 inhibitor (PDE5-I), at lower dose, but not at higher doses, was reported previously. Hence, present work was undertaken to study the effects of tadalafil (TAD), another PDE5-I, per se and in combination with L-NAME in forced swimming test (FST) in rat for 14 days. TAD (5 mg/kg, p.o.) significantly reduced immobility duration, increased swimming duration on day 1 and 14, and increased climbing frequency on day 14 as compared to normal group. Whereas, TAD (10 and 20 mg/kg, p.o.) insignificant in this regards. On day 1 and 14, L-NAME (20 mg/kg, i.p.) showed reduction in immobility duration and increase in swimming duration and climbing frequency. L-NAME (20 mg/kg) after TAD (20 mg/kg) reduced immobility duration and increased swimming duration on day 1 and 14 and increased climbing frequency on day 14 as compared to normal group. Tadlafil, at low dose but not at higher dose, has antidepressant-like effect on behavior in FST. L-NAME has antidepressant-like effect on behavior in FST. L-NAME does not interact with tadalafil (20 mg/kg) in regards of effects on behavior in FST. The results showed that, tadalafil produced dose dependent but time-independent effect on immobility and swimming whereas dose and time dependent effect on climbing was evident.

AB041. Evolution of PDE5 inhibitors in Korea

After launching of Sildenafil Citrate, the last invention of 20th century, in 1998, oral PDE5 inhibitor has been established as first line treatment of erectile dysfunction (ED) and shift new paradigm of diagnosis and treatment of ED. The big success of sildenafil in pharmaceutical R&D induced the consecutive development of the so-called ‘The second viagra’, e.g., Tadalafil and Vardenafil in 2003. Currently, these 3 kinds of PDE5 inhibitors are most famous and well-known PDE5 inhibitors worldwide. In Korea, another 3 kinds of PDE5 inhibitors, Udenafil (2005), Mirodenafil (2007) and Avanafil (2011) have been developed and 6 kinds of PDE5 inhibitors were used in the competitive market. In last 10 years, the evolution of PDE5 inhibitors competition has changed the dosage concept from on-demand to daily low-dose and applied for other indications beyond ED such as pulmonary hypertension in Sildenafil, and BPH/LUTS in Tadalafil and penile rehabilitation with daily low dose. For the preparations of PDE5 inhibitors, the termination of Korean patent of sildenafil in 2012 released 4 preparations of PDE5 inhibitors, tablet, oro-disposable film, granule and chewable of 60 generic Sildenafil from 49 companies. The oro-disposable film and chewable are favorable from patients. In Korea, patent of Cialis will be terminated in near future and the development of generic drugs like Viagra will go in the right way and as expected. The long half-life of Tadalafil enabled the approval for BPH/LUTS with daily low dose usage. In turn, the generic Cialis also will be developed as various preparations including oro-disposable film and as combination with antihypertensive for ED/HT, PDE5 inhibitor with alpha blockers for ED/LUTS and PDE5 inhibitor with antidepressant for ED/PE. The present lecture review the evolution of PDE5 inhibitors from the development of sildenafil citrate in 1998 to combination in 2015, Korea.

Involvement of NO-cGMP pathway in anti-hyperalgesic effect of PDE5 inhibitor tadalafil in experimental hyperalgesia.

The association of elevated level of cyclic guanosine monophosphate (cGMP) with inhibition of hyperalgesia and involvement of nitric oxide (NO)-cGMP pathway in the modulation of pain perception was previously reported. Phosphodiesterases 5 (PDE5) inhibitors, sildenafil and tadalafil (TAD) used in erectile dysfunction, are known to act via the NO-cGMP pathway. TAD exerts its action by increasing the levels of intracellular cGMP. Hence, the present study investigated the effect of TAD 5, 10, or 20mg/kg, per os (p.o.) or L-NAME 20mg/kg, intraperitoneally (i.p.) and TAD (20mg/kg, p.o.) in carrageenan- and diabetes-induced hyperalgesia in rats using hot plate test at 55±2°C. In carrageenan- and diabetes-induced hyperalgesia, TAD (10 and 20mg/kg, p.o.) significantly increased paw withdrawal latencies (PWLs) as compared to the control group. L-NAME significantly decreased PWLs as compared to the normal group and aggravated the hyperalgesia. Moreover, significant difference in PWLs of L-NAME and TAD 20 was evident. Co-administration of L-NAME (20mg/kg) with TAD (20mg/kg) showed significant difference in PWLs as compared to the TAD (20mg/kg), indicating L-NAME reversed and antagonized TAD-induced anti-hyperalgesia. This suggested an important role of NO-cGMP pathway in TAD-induced anti-hyperalgesic effect.

Association Between Erectile Dysfunction Drugs and Malignant Melanoma

Previous studies have suggested that risk for malignant melanoma is elevated in users of phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, vardenafil, tadalafil) for erectile dysfunction. A theoretical biologic mechanism exists: Downregulation of PDE5 is thought to increase invasiveness of melanoma. Researchers identified 4065 Swedish men with incident malignant melanoma and …

Validated spectrofluorimetric method for determination of two phosphodiesterase inhibitors tadalafil and vardenafil in pharmaceutical preparations and spiked human plasma.

A valid, sensitive and rapid spectrofluorimetric method has been developed and validated for determination of both tadalafil (TAD) and vardenafil (VAR) either in their pure form, in their tablet dosage forms or spiked in human plasma. This method is based on measurement of the native fluorescence of both drugs in acetonitrile at λem 330 and 470 nm after excitation at 280 and 275 nm for tadalafil and vardenafil, respectively. Linear relationships were obtained over the concentration range 4-40 and 10-250 ng/mL with a minimum detection of 1 and 3 ng/mL for tadalafil and vardenafil, respectively. Various experimental parameters affecting the fluorescence intensity were carefully studied and optimized. The developed method was applied successfully for the determination of tadalafil and vardenafil in bulk drugs and tablet dosage forms. Moreover, the high sensitivity of the proposed method permitted their determination in spiked human plasma. The developed method was validated in terms of specificity, linearity, lower limit of quantification (LOQ), lower limit of detection (LOD), precision and accuracy. The mean recoveries of the analytes in pharmaceutical preparations were in agreement with those obtained from the comparison methods, as revealed by statistical analysis of the obtained results using Student's t-test and the variance ratio F-test.

A REVIEW OF ANALYTICAL METHODS FOR ESTIMATION OF TADALAFIL IN PHARMACEUTICAL FORMULATIONS

Tadalafil (TAD) is a selective phosphodiesterase type 5 inhibitor. It is utilized for the treatment of erectile dysfunction (ED) and pulmonary arterial hypertension (PAH). It enhances the sexual performance in males during copulation. It is recommended in the guidelines as first-line therapy, because of convenience, high efficacy and low rates of side effects. As a result of the importance of this phosphodiesterase inhibitor agent in the treatment of ED, this work aims to compile the published analytical methods reported so far in the literature, for determination of TAD in biological samples and pharmaceutical formulations. Techniques like UV-VIS spectrophotometry, spectrofluorimetry, high - performance liquid – chromatography (HPLC), high - performance thin - layer chromatography (HPTLC), gas chromatography – mass spectrometry (GC-MS), liquid chromatography – mass spectrometry (LC-MS) with electrospray ionisation have been used for analysis, while high-performance liquid chromatography methods have been used most extensively.

Sexual function in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia: results of a 6-month, randomized, double-blind, placebo-controlled study of tadalafil coadministered with finasteride.

Tadalafil (TAD) 5 mg coadministered with finasteride (FIN) 5 mg significantly improves lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) and prostatic enlargement. However, its effects on erectile/sexual function have yet to be fully described. Assess the effects of TAD/FIN coadministration (compared with placebo [PBO]/FIN) on erectile and sexual function in sexually active men with LUTS and prostatic enlargement secondary to BPH with or without baseline comorbid erectile dysfunction (ED). A randomized, double-blind, PBO-controlled study of 695 men (610 sexually active; 450 with baseline ED; 404 sexually active with baseline ED) conducted at 70 sites in 13 countries. TAD 5 mg or PBO once daily coadministered with FIN 5 mg once daily for 26 weeks. International Index of Erectile Function (IIEF) domain and single-item scores; proportions of patients who demonstrated minimal clinically important differences (MCIDs) in IIEF-Erectile Function domain scores (IIEF-EF; MCID defined as ≥4-point improvement); and sexual dysfunction adverse events (AEs). Compared with PBO/FIN, TAD/FIN resulted in improvements for all IIEF domain and single-item scores assessed among patients with baseline ED (P ≤ 0.002 for all measures) and among patients without baseline ED (P ≤ 0.041 for all measures). Compared with PBO/FIN, significantly larger percentages of sexually active men with baseline ED treated with TAD/FIN achieved an IIEF-EF MCID after 4, 12, and 26 weeks of therapy (P < 0.001 for odds ratio comparisons between TAD/FIN and PBO/FIN at all 3 three postbaseline timepoints). The incidence of sexual AEs was low: five TAD/FIN patients and seven PBO/FIN patients reported sexual AEs, including ED, decreased/lost libido, and ejaculation disorders. TAD/FIN coadministration for the treatment of men with LUTS and prostatic enlargement secondary to BPH concurrently leads to statistically significant improvements in erectile/sexual function and is well-tolerated, regardless of the presence/absence of ED at treatment initiation.

Adcirca contraindicated with riociguat

Adcirca contraindicated with riociguat

A novel liquid chromatographic method with fluorescence detection for quantitation of tadalafil and dapoxetine hydrochloride in pharmaceutical dosage form and human plasma.

Tadalafil (TAD) and dapoxetine HCl (DAP) are recently co-formulated and both show native fluorescence. Therefore, a novel, accurate, specific and sensitive reversed-phase high performance liquid chromatographic method with fluorescence detection was developed and validated for their separation and quantitation in dosage form and human plasma using avanafil as an internal standard (IS). Separation was achieved using isocratic elution within 7.0 min on C18 column and acetonitrile-0.15% triethylamine (40:60, v/v; pH 4) as a mobile phase. The flow rate was 1.0 mL/min and the detection was time-programmed at 330, 410 and 370 nm for TAD, DAP and IS, respectively, after excitation at 236 nm. The linear ranges from 0.01 to 30.00 μg/mL for each drug with the limits of detection of 4.20 and 7.20 ng/mL for TAD and DAP, respectively. The method was validated in accordance to the International Conference on Harmonization (ICH) guidelines and was successfully applied to spiked human plasma with mean recoveries of 98.17% and 98.83% for TAD and DAP respectively.

Comparative efficacy of tadalafil once daily in men with erectile dysfunction who demonstrated previous partial responses to as-needed sildenafil, tadalafil, or vardenafil

Objective:Phosphodiesterase type-5 inhibitors (PDE5Is) are first-line therapies for erectile dysfunction (ED). Sildenafil (SIL) and vardenafil (VAR) are approved for as-needed (PRN) dosing; tadalafil (TAD) is approved for both PRN and once-a-day (OaD) dosing for ED. Recent evidence suggests that TAD-OaD may be effective as therapy in men with an incomplete response to PRN-PDE5I therapy. This study evaluated whether TAD-OaD provides similar efficacy in men with ED who had previously demonstrated a partial response to PRN-PDE5I therapy.Research design and methods:In this randomized, double-blind, placebo-controlled trial, men with a ≥3 month ED history received SIL 100 mg, TAD 20 mg, or VAR 20 mg during a 4 week open-label lead-in period. Those with International Index of Erectile Function – Erectile Function (IIEF-EF) domain scores <26 following lead-in treatment completed a 4 week washout period, then randomized to TAD 2.5 mg up-titrated to 5 mg, TAD 5 mg, or placebo (PBO) OaD for 12 weeks. Main outcome measures obtained from patients treated with TAD-OaD were compared to PBO-treated patients. Additionally, results of treatment with TAD-OaD were compared to results obtained from 4 week PRN-PDE5I therapy to determine whether OaD and PRN regimens provided comparable efficacy.Clinical trial registration:NCT01130532.Main outcome measures:International Index of Erectile Function (IIEF) domain scores; Sexual Encounter Profile (SEP) questions 2–5.Results:Endpoint data was obtained from 590 men (391 TAD; 199 PBO). Results for all IIEF and SEP measures were significantly better for TAD-OaD (p < 0.001 for all) compared to PBO and were comparable to those observed during PRN-PDE5I treatment. TAD 2.5 mg and TAD 5 mg OaD therapy were safe and generally well tolerated.Conclusion:Tadalafil once daily is a viable alternative to as-needed PDE5I therapy in men with ED. Key limitations include the lack of a PRN PDE5I study group during the double-blind period, and that many more patients took tadalafil than sildenafil or vardenafil during the PRN period.

Reversal of severe angioproliferative pulmonary arterial hypertension and right ventricular hypertrophy by combined phosphodiesterase-5 and endothelin receptor inhibition.

BackgroundPatients with pulmonary arterial hypertension (PAH) are treated with vasodilators, including endothelin receptor antagonists (ERAs), phosphodiesterase-5 (PDE-5) inhibitors, soluble guanylyl cyclase activators, and prostacyclin. Despite recent advances in pharmacotherapy for individuals with PAH, morbidity and mortality rates in this patient population remain unacceptably high. Here, we tested the hypothesis that combination therapy with two PAH drugs that target distinct biochemical pathways will provide superior efficacy relative to monotherapy in the rat SU5416 plus hypoxia (SU-Hx) model of severe angioproliferative PAH, which closely mimics the human condition.MethodsMale Sprague Dawley rats were injected with a single dose of SU5416, which is a VEGF receptor antagonist, and exposed to hypobaric hypoxia for three weeks. Rats were subsequently housed at Denver altitude and treated daily with the PDE-5 inhibitor, tadalafil (TAD), the type A endothelin receptor (ETA) antagonist, ambrisentan (AMB), or a combination of TAD and AMB for four additional weeks.ResultsMonotherapy with TAD or AMB led to modest reductions in pulmonary arterial pressure (PAP) and right ventricular (RV) hypertrophy. In contrast, echocardiography and invasive hemodynamic measurements revealed that combined TAD/AMB nearly completely reversed pulmonary hemodynamic impairment, RV hypertrophy, and RV functional deficit in SU-Hx rats. Efficacy of TAD/AMB was associated with dramatic reductions in pulmonary vascular remodeling, including suppression of endothelial cell plexiform lesions, which are common in human PAH.ConclusionsCombined therapy with two vasodilators that are approved for the treatment of human PAH provides unprecedented efficacy in the rat SU-Hx preclinical model of severe, angioproliferative PAH.

Comparison of sertraline plus doxazosin and tadalafil in the treatment of premature ejaculation

Objective To compare the efficacy and safety of sertraline plus doxazosin and tadalafil in the treatment of premature ejaculation (PE).Methods From Feb.to Aug.2011,One hundred and five patients from 19 to 52 years old with PE but without any obvious organic cause were enrolled in this study.They were randomly divided into Groups A,B and C in equal number.All the three Groups received 50 mg sertraline daily 4 to 6 hours before planned sexual activity for 12 weeks,Group B were added with 4 mg Doxazosin every day 8 to 9 hour before planned sexual activity,and Group C were given 20 mg Tadalafil as needed one hour before planned sexual activity.The mean intravaginal ejaculatory latency time,the mean intercourse satisfaction domain values and the sexual activity satisfaction domain values of the patient couples of group A before treatment were 0.6±±0.1 min,8.3±1.3,5.3±1.4; Group B were 0.6±0.1 min,7.6± 1.5,5.6± 1.5 ; Group C were 0.6±0.1 min,8.1 ± 1.1,5.0± 1.2,respectively.We observed before and after the treatment for 12 weeks and the effects were evaluated.Results The mean intravaginal ejaculatory latency time,the mean intercourse satisfaction domain values and the sexual activity satisfaction domain values of the patient couples of group A were 3.9±0.l min,10.6±0.1,9.7±0.1,respectively; Group B were 4.5 ± 0.1 min,12.8±1.3,11.9±1.6; Group C were 5.6±0.3 min,14.6±1.4,13.1±1.5,respectively.The mean intravaginal ejaculatory latency time improved in all of the 3 groups,but more significantly in Group B and C (P＜0.05).The mean intercourse satisfaction domain values of the IIEF were significantly greater in Group B and C than in Group A (P＜0.05) after the treatment; and the sexual activity satisfaction domain values of the patient couples were greater in Group C than in Group B after the treatment,but it is not significant.As for the side effects,5 cases in group A felt headaches and dizzy (14.3％),8 cases in group B felt headaches and dizzy (22.9％),and in group C,9 cases felt headaches and dizzy (25.7％),6 cases experienced flushing episodes on the body (17.1％).there was a higher rate of headaches (P＜0.05) and flushing episodes (P＜0.05) in Group B and C than in Group A.Conelusions Sertraline combined with Tadalafil or Doxazosin can achieve significantly better results than sertraline alone in patients with premature ejaculation.However,the combined treatment is associated with a slightly increased in the drug related side effects,and there is no significant difference in the efficacy of Sertraline Plus Tadalafil or Doxazosin in the treatment of premature ejaculation. Key words: Tadalafil; Sertraline; Doxazosin; Premature ejaculation

AB167. Efficacy and safety of long-term tadalafil 5 mg once daily combined with sildenafil 50 mg as needed at the early stage of treatment for patients with erectile dysfunction

This study aimed to evaluate the efficacy and safety of long-term and low-dose tadalafil combined with sildenafil as needed at the early stage of treatment for erectile dysfunction (ED). We enrolled 180 patients with ED 1:1 to tadalafil 5 mg once daily or once-a-day tadalafil 5 mg combined with sildenafil 50 mg as needed. The efficacy measures included the 5-item version of the international index of erectile function (IIEF-5) and the sexual encounter profile (SEP). The safety was assessed by observing drug tolerability and adverse events. Total IIEF-5 scores of patients with severe ED in combined medication group were significantly higher than in tadalafil alone group. Question 2 scores of IIEF-5 of patients with moderate and severe ED in combined medication group were significantly higher than in tadalafil alone group. The significant improvement in question 3 scores of IIEF-5 existed only in patients with severe ED receiving combined medication. The percentage of ‘yes’ responses to SEP4, SEP5 and partner’s SEP3 were improved significantly in combined medication group. There was no difference between two groups in the incidence of adverse events. Our results suggest that combined medication can better improve erectile function, especially for patients with severe ED.

AB25. What would YES (Morning Erection/Sleep-related Erection) be without NO (Nitric Oxide) induced by Teststerone?

As you know, for penile erection, a sufficient amount of testosterone-induced nitric oxide is needed in the smooth muscle of the penile arterial wall. With aging, LOH syndrome and so on, the serum testosterone level decreases, resulting in a decline of penile erectile function. Furthermore, it is known that the enzyme PDE5 in the penile artery wall also inhibits that function. Even so, it may be safe to say that decreasing testosterone is the major factor for erectile dysfunction, excepting severe diabetic arterial sclerosis. Currently, however, almost all doctors treat ED cases with a PDE5-Inhibitor only. From my understanding of the above-mentioned mechanism of erection, I think this medical treatment is not scientific and only a half measure. Cases in which PDE5-inhibitors alone are effective are limited to those in which sufficient NO is maintained to barely induce erection unless inhibited by PDE5. Aging males, especially, have lower NO levels caused by low testosterone. These cases cannot be cured satisfactorily by PDE5 inhibitors alone, even if the men can somehow achieve sexual intercourse. Therefore, I cannot understand or agree with the treatment method using a PDE5-Inhibitoralone without checking the testosterone level. Furthermore, simple temporal recovery of sexual activity does not revitalize the male fundamental physiology, that is, sleep-related erection and morning erection. And a more important problem is that latent psychological disorders should be thoroughly investigated for patients consulting about so-called ED. It is even said that it is lucky for a patient to have a chance to consult about ED, since it means that the doctor will check for other disorders; for example, metabolic syndrome so on. More aged men are beginning to feel loss of motivation and poor physiological condition after the climacteric stage, with loss of morning erection, even if they do not express complaints. These problems are mostly caused by a decline in testosterone, which latently accelerates arterial sclerosis and vascular disorders, shortening the male life span. Such patients with low levels of free testosterone complaining of ED should be treated with testosterone substitution and a PDE9-inhibitor (especially long-acting Cialis) for a period of at least 2-3 months. This treatment will restore the male physiological functions of sleep-related erection and morning erection and as well as treating many symptoms of LOH syndrome at the same time. However, the most important effect of revitalization of male physiology is surely the restoration of the self-actualization and dignity of maleness to patients. That should be considered the most clinically significant outcome.

AB51. PDE5 expression in the prostate: where is it really?

PDE5 inhibitor Tadalafil has been approved for the treatment of BPH symptoms, but where PDE5 is expressed in the prostate remains a mystery. In the literature five studies have reported immunolocalization of PDE5 in the prostate. Uckert et al. concluded that PDE5 is mainly expressed in the glandular structure, but Zenzmaier et al., Fibbi et al., Morelli et al., and Zhang et al. all said that PDE5 is undetectable in the epithelium. Still, while Zenzmaier et al. and Zhang et al. found that PDE5 is mainly expressed in the fibromuscular stroma, Fibbi et al. and Morelli et al. said that PDE5 is undetectable in the fibromuscular stroma and is mainly expressed in the vascular endothelium and smooth muscle. However, it should be noted that the histological images in the latter studies were acquired at 4× or 10× magnifications, which are too low for discerning such structures.In each of these five studies PDE5 expression was investigated only as a companion or side issue. In fact, regardless of the findings, the location of PDE5 expression has little or no relevance to these studies’ main outcomes. However, when put together for reference or review, these studies cause considerable confusions. As such, we recently conducted a dedicated investigation on PDE5 expression in rat prostate. By using Western blot analysis we found that PDE5 was expressed at a significantly lower level in dorsal lobe (DL) than in ventral lobe (VL) or lateral lobe (LL). By using immunohistochemistry and immunofluorescence we found that PDE5 was expressed in both acinar epithelium and periacinar smooth muscle. However, while similar levels of smooth muscle PDE5 expression were observed in all three prostatic lobes, significantly lower level of epithelial PDE5 expression was found in DL compared to VL or LL. In prostatic blood vessels PDE5 expression was clearly visible in the endothelium but not as easily detectable in the smooth muscle. Regardless, the acinar wall, not the blood vessel wall, is the predominant PDE5 expression site in rat prostate.

AB151. Clinical study on the treatment of lifelong premature ejaculation with paroxetine hydrochloride and tamsulosin

Background and objectiveThere are some methods for the treatment of primary premature ejaculation (PE) at present, but its efficacy and safety is not very good and the effectiveness of some treatment method remains to be further confirmed. Psychotherapy and behavior training therapy has a poor adherence for patients. The surgical treatment to PE has not been widely recognized by experts because its effect of uncertainty and may cause irreversible damage. So, pharmaceutical drug therapy is usually recommended as the first priority selection for the treatment of PE. At present, only the dapoxetine was specifically developed for the treatment of PE worldwide. Other off-label selective serum reuptake inhibitor substance (SSRIs) such as paroxetine, fluoxetine; local anesthetics such as lidocaine, prilocaine cream; PDE5 inhibitor such as tadalafil, sildenafil and vardenafil; selective alpha-adrenergic receptor blockers such as tamsulosin, silodosin was also used for the treatment of PE. Owing to the individual differences and the different causes of PE, the efficacies of one medicine in different patients are different. So, individual-based treatment could be the trend for the treatment of PE according to the specific causes and its classification. There is quite a few researches focus on the combination treatment of SSRIs and α-receptor blockers to PE. In this study, the efficacy and safety using paroxetine and hydrochloric tamsulosin for the treatment of PE were evaluated, the serum concentration of 5-HT in the PE patients before and after treatment were assessed, and the mechanism of SSRIs for the treatment of PE were discussed.MethodsA total of 225 cases of men with 18-65 years of age, a history of lifelong PE and an intra-vaginal ejaculation latency time (IELT) <120 sec were included in this study. The patients were randomized divided into three groups. Group A were given paroxetine hydrochloride 20 mg/d for 8 weeks; group B were given tamsulosin 0.2 mg/d for 8 weeks; group C were given paroxetine hydrochloride and tamsulosin at the same dosage as above for 8 weeks. The effects and adverse events were evaluated by the overall change and folds increase in average IELT and the mean change in all four measures of the premature ejaculation profile (PEP). Blood sample was got from the candidates before and after treatment. The plasma concentration of 5-HT was measured by ELISA. All the data were statistically analyzed.ResultsThe reliable data from 198 patients were achieved. The mean IELT in group A was increased from 1.23 to 8.52 min and increased for 7.29 min after treatment; the mean IELT in group B was increased from 1.16 to 2.30 min and increased for 1.14 min after treatment; the mean IELT in group C was increased from 1.16 to 9.31 min and increased for 8.15 min after treatment; the mean IELT after treatment were significantly improved in all groups than that of before treatment (group B: P<0.01; group A,C: P<0.001). The increased folds of mean IELT in group C (8.02 folds) was significantly higher than that in group B (1.98 folds) and group A (6.92 folds) (P<0.001). The mean PEP scores that include measures of perceived control over ejaculation, satisfaction with sexual intercourse, ejaculation-related personal distress, and ejaculation-related interpersonal difficulty were significantly improved in all groups after treatment. The mean PEP scores in group C have more significant improvements than that in group A and B. The prevalence of adverse events in group A,B,C were 13.3% (10 cases), 2.6% (2 cases) and 12.0% (9 cases), respectively. The mean plasma concentration of 5-HT in group A,B,C before treatment was significant lower than that in normal control group (P<0.001). The mean plasma concentration of 5-HT in group A and C was significant improved (P<0.001) and there is no significant difference between group A and C after treatment (P>0.05). The plasma concentration of 5-HT in group B did not change after treatment (P>0.05).ConclusionsParoxetine hydrochloride combined with tamsulosin produce more better therapeutic effects and could be a priority selection for the treatment of primary PE. The plasma concentration of 5-HT can be used as the objective diagnostic index of primary PE, and to some extent, it is meaningful for the assessment of treatment effect of SSRIs.

Thermodynamics and solubility of tadalafil in diethylene glycol monoethyl ether + water co-solvent mixtures at (298.15 to 333.15) K

Temperature dependent solubility data of tadalafil (TDL) in diethylene glycol monoethyl ether (Transcutol)+water co-solvent mixtures are not available in literature. Therefore, the aim of present study was to determine the temperature dependent solubility data of crystalline TDL in mono-solvents and various Transcutol+water co-solvent mixtures from 298.15 to 333.15K at atmospheric pressure. The experimental solubilities of crystalline TDL were measured using the shake flask method. The experimental solubilities were correlated with the Apelblat model. The solubilities of crystalline TDL were regressed by Apelblat equation with a relative deviation in the range of 0.02 to 6.81% in all co-solvent mixtures investigated at 298.15 to 333.15K. The root mean square deviations were observed in the range of 0.013 to 0.058. However, the correlation coefficients were observed in the range of 0.996 to 0.999. The solubility of crystalline TDL was found to be increased with increase in temperature and mass fraction of Transcutol in co-solvent mixtures. The mole fraction solubility of crystalline TDL was observed highest in pure Transcutol (8.76×10−3 at 298.15K) as compared to water (5.74×10−7 at 298.15K). Around 15,263 fold enhancements in solubility of crystalline TDL in Transcutol were observed as compared to its aqueous solubility at 298.15K. The dissolution of TDL in most of the co-solvent mixtures was assumed to be non-spontaneous, endothermic and an entropy driven process. Overall, the results of these studies indicated that Transcutol could be used as a co-solvent in formulation development especially in terms of liquid dosage forms of crystalline TDL.

Electrochemical behavior of tadalafil on TiO2 nanoparticles–MWCNT composite paste electrode and its determination in pharmaceutical dosage forms and human serum samples using adsorptive stripping square wave voltammetry

A sensitive and selective electroanalytical method for the determination of tadalafil (TAD) using adsorptive stripping square wave voltammetry at multiwalled carbon nanotube paste electrode (MWCNTPE) and modified TiO2-multiwalled carbon nanotube paste electrode (TiO2-MWCNTPE) was presented. The calibration curves were linear in the concentration range of 3.6–8.1 and 12.7–61.1 μM on MWCNTPE, 0.27–15.2 μM on TiO2-MWCNTPE. The recommended method was successfully applied to the determination of the drug in tablets and human serum samples with good recoveries. The selectivity of the proposed method was considered in the presence of Ca2+, K+, Na+, 2-mercapto benzimidazole, thiourea, and dopamine by means of recovery tests. Interfering agents did not show considerable effect on TAD determination. No electroactive interferences from the tablet excipients and endogenous substances from biological material were detected. The possible electrooxidation pathway and the number of transferred electrons were also investigated.

Tadalafil Might Ease Symptoms of Benign Prostatic Hyperplasia

Phosphodiesterase-5 inhibitors are known mainly for treating erectile dysfunction, but one of them — tadalafil (Cialis) — also is FDA-approved for

MP48-10 TADALAFIL ONCE A DAY SIGNIFICANTLY REDUCES PENILE LENGTH-LOSS IN PATIENTS POST BILATERAL NERVE-SPARING RADICAL PROSTATECTOMY (NSRP) - RESULTS FROM A RANDOMIZED CONTROLLED TRIAL

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Medical and Non-surgical1 Apr 2014MP48-10 TADALAFIL ONCE A DAY SIGNIFICANTLY REDUCES PENILE LENGTH-LOSS IN PATIENTS POST BILATERAL NERVE-SPARING RADICAL PROSTATECTOMY (NSRP) - RESULTS FROM A RANDOMIZED CONTROLLED TRIAL Gerald Brock, Francesco Montorsi, Pierre Costa, Nimish Shah, Jose Maria Martinez Jabaloyas, Peter Hammerer, Giuseppe M. Ludovico, Carsten Henneges, Karim Hamidi, Andrea Rossi, Hartwig Büttner, and John Mulhall Gerald BrockGerald Brock More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Pierre CostaPierre Costa More articles by this author , Nimish ShahNimish Shah More articles by this author , Jose Maria Martinez JabaloyasJose Maria Martinez Jabaloyas More articles by this author , Peter HammererPeter Hammerer More articles by this author , Giuseppe M. LudovicoGiuseppe M. Ludovico More articles by this author , Carsten HennegesCarsten Henneges More articles by this author , Karim HamidiKarim Hamidi More articles by this author , Andrea RossiAndrea Rossi More articles by this author , Hartwig BüttnerHartwig Büttner More articles by this author , and John MulhallJohn Mulhall More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1484AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Secondary analyses on stretched penile length (SPL) data from a multicenter, randomized, double-blind, double-dummy, placebo (PLC) controlled clinical trial (NCT01026818) evaluating the efficacy of tadalafil (TAD) initiated post-nsRP are reported. Methods Patients (pts) ≤68yrs with normal preoperative erectile function (EF) who underwent nsRP for localized prostate cancer (Gleason ≤7, PSA <10ng/mL) were randomized post nsRP 1:1:1 to 9-month (mo) double-blind treatment (DBT) with TAD 5mg once a day (OaD), 20mg TAD on demand (pro re nata; PRN), or PLC, followed by 6-week drug-free washout (DFW)and 3mo open-label OaD treatment (OLT, all pts). Secondary outcome measures included change of SPL from baseline (nsRP) to end of 9mo DBT (eDBT)(LS mean change compared by prespecified ANCOVA, including terms for treatment, country, baseline, age, and Nerve Sparing Score [NSS]), responses to Sexual Encounter Profile Questions (SEP) 1 and 3 (mixed model for repeated measures including terms for treatment, country, visit, visit-treatment interaction, age) and the Standardized Morning Erection Question (SMEQ; Cochrane Mantel Haenszel test adjusted for age and country). Results 423 pts were randomized to OaD (N=139), PRN (N=143), and PLC (N=141); 114/122/155 completed 9mo DBT. Greater retained SPL was observed with OaD vs PLC at eDBT (Figure; LS mean [95%CI] difference OaD vs PLC, 4.1 [0.4, 7.8] mm, p=0.032). No significant LS mean difference (p >0.05) was observed for PRN vs PLC. No significant effect of NSS on SPL loss was observed (Figure). Penile tumescense (SEP 1) as the initial sign of EF recovery was improved significantly vs. PLC at eDBT and OLT for pts randomized to OaD only. The ability for sexual intercourse (SEP 3) also significantly improved for pts on OaD vs placebo only at eDBT. The distribution of SMEQ responses was different at eDBT (p=0.045), with 34.2% of pts on OaD, 50.0% on PRN and 56.5% on PLC reporting the absence of morning erections, At eDFW, SEP responses were not statistically significantly different between OaD and PLC. Conclusions These data suggest that the early initiation of treatment with TAD OaD protects from penile length-loss and may contribute to protection from structural cavernosal changes post nsRP. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e530-e531 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Gerald Brock More articles by this author Francesco Montorsi More articles by this author Pierre Costa More articles by this author Nimish Shah More articles by this author Jose Maria Martinez Jabaloyas More articles by this author Peter Hammerer More articles by this author Giuseppe M. Ludovico More articles by this author Carsten Henneges More articles by this author Karim Hamidi More articles by this author Andrea Rossi More articles by this author Hartwig Büttner More articles by this author John Mulhall More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...