Tadalafil

Tadalafil, also known as IC351 or Cialis, is a potent, reversible and competitive small-molecule inhibitor of phosphodiesterase 5 (PDE5), a predomiant PDE in the pulmonary vasculature that hydrolyzes cyclic guanosine monophosphate (cGMP) and is involved in the pathobiology of pulmonary arterial hypertension (PAH). The inhibitory effect of tadalafil is PDE5 specific with the selectivity of 10000 times greater than that of PDE1, PDE4, PDE7, PDE8, PDE9 and PDE10 and of 780 times greater than that of PDE6. Although it is used for the treatment of erectile dysfunction through oral administration, tadalafil also improves the vasoconstrictive-predominate condition of PAH through elevating cGMP levels in pulmonary vessels resulted from PDE5 inhibition.

Reference

Fusae Sawamura, Masami Kato, Kazushisa Fujita, Takahiro Nakazawa and Anthony Bearsworth. Tadalafil, a long-acting inhibitor of PDE5, improves pulmonary hemodynamics and survival rate of monocrotaline-induced pulmonary artery hypertension in rats. J Pharmacol Sci 111, 235-243 (2009)

H Porst. IC351 (tadalafil, Cialis): update on clinical experience. Internation Journal of Impotence Research (2002) 14, Suppl 1, S57-S64

S. Thomas Forgue, Beverley E. Patterson, Alun W. Bedding, Christopher D. Payne, Diane L. Phillips, Rebecca E. Wrishko and Malcolm I. Mitchell. Tadalafil pharmacokinetics in healthy subjects. Br J Clin Pharmacol (2005); 61(3): 280-288

[Tadalafil Ameliorates Symptoms of Patients with Benign Prostatic Hyperplasia Complicated by Chronic Pelvic Pain Syndrome].[Pubmed:28331166]

Hinyokika Kiyo. 2017 Mar;63(3):101-105.

To examine the efficacy and safety of Tadalafil in the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia with chronic pelvic pain syndrome, we treated 23 Japanese men with Tadalafil 5 mg once daily for 4 weeks. The mean age of the participantswas58.7 yearsand the prostate volume was25. 2 ml. Significant improvementsin total International Prostatic Symptom Score, International Prostatic Symptom Score Quality of Life Index, total National Institutes of Health Chronic Prostatitis Symptom Index score, pain subscore, urinary symptom subscore, and quality of life impact subscore, were observed for Tadalafil versus before treatment. These findings confirm that Tadalafil is a valuable new treatment option for patients with benign prostatic hyperplasia complicated by chronic pelvic pain syndrome.

The renoprotective effect of oral Tadalafil pretreatment on ischemia/reperfusion injury in rats.[Pubmed:28300873]

Acta Cir Bras. 2017 Feb;32(2):90-97.

PURPOSE: To evaluate the effect of Tadalafil in renal ischemia/reperfusion (I/R) injury in rats Methods: Group I/R saline rats (n=6) were subjected to 45 minutes of left renal ischemia and treated with saline; the I/R Tadalafil rats (n=6) received oral 10mg/kg Tadalafil microemulsion one hour before ischemia. In both groups, 8 hours after ischemia, laboratory analysis were performed Results: Better tissue perfusion was lower in ischemic left/kidney than in right/kidney in saline group, suggesting reduced kidney clearance. Fluorescence in left/kidneys of Tadalafil treated rats was lower than in right/kidneys (difference not significant). The fluorescence signal intensity in kidneys of tadafil treated rats was higher than in saline rats. TNF-alpha levels were significantly lower in I/R Tadalafil group rats compared to I/R saline group (154+/-10.3 vs 391.3+/-12.3), as well as IL-1beta (163.4+/-13.2 vs 279+/-11.5pg/dL), and IL-6 (122.9+/-8.1 vs 173.7+/-6.3 respectively; p=0.0001). Urea, creatinine and C-reactive protein were significantly lower in tadafil treated rats then in saline group Conclusion: Tadalafil therapy decreased the expression of circulating pro-inflammatory cytokines in a renal I/R rodent model, while improving kidney function proofs.

Effects of taking tadalafil 5 mg once daily on erectile function and total testosterone levels in patients with metabolic syndrome.[Pubmed:28295481]

Andrologia. 2017 Nov;49(9).

We aimed to evaluate the efficacy of Tadalafil 5 mg once-daily treatment on testosterone levels in patients with erectile dysfunction (ED) accompanied by the metabolic syndrome. A total of 40 men with metabolic syndrome were evaluated for ED in this study. All the patients received 5 mg Tadalafil once a day for 3 months. Erectile function was assessed using the five-item version of the International Index of Erectile Function (IIEF) questionnaire. Serum testosterone, follicle-stimulating hormone and luteinising hormone levels were also evaluated, and blood samples were taken between 08.00 and 10.00 in the fasting state. All participants have three or more criteria of metabolic syndrome. At the end of 3 months, mean testosterone values and IIEF scores showed an improvement from baseline values (from 3.6 +/- 0.5 to 5.2 +/- 0.3, from 11.3 +/- 1.9 to 19 +/- 0.8 respectively). After the treatment, serum LH levels were decreased (from 5.6 +/- 0.6 to 4.6 +/- 0.5). There was significantly difference in terms of baseline testosterone and luteinising hormone values and IIEF scores (p < .05). Based on our findings, we recommend Tadalafil 5 mg once daily in those men with erectile dysfunction especially low testosterone levels accompanied by metabolic syndrome.

A randomized single-center study to compare the efficacy and tolerability of tadalafil once daily plus lidocaine anesthetic spray on premature ejaculation.[Pubmed:28338191]

Eur Rev Med Pharmacol Sci. 2017 Mar;21(5):1036-1040.

OBJECTIVE: The use of topical local anesthetics in the form of creams, gel or spray is the oldest method of retarding ejaculation. However, several studies have suggested that phosphodiesterase type 5 inhibitors (5-PDEiS) show a potential therapeutic use in the treatment of premature ejaculation (PE). The aim of this study was to compare the efficacy and tolerability of Tadalafil-only, Tadalafil plus local anesthetic spray (lidocaine), and topical lidocaine spray-only before intercourse on the intravaginal ejaculatory latency time (IELT) of patients with lifelong PE. PATIENTS AND METHODS: The study included 78 men in stable heterosexual, monogamous relationships (of >/=3 months) who were diagnosed with lifelong PE. The patients were divided into three groups: G1: 25 patients who received lidocaine spray 10 g/100 ml at 5 min before intercourse; G2: 27 patients who received Tadalafil 5 mg once daily; G3: 26 patients who treated with Tadalafil once daily plus lidocaine spray before planned sexual activity. The treatments were continued for up to three months in all groups. Moreover, the quality of their sexual attempts was rated on a 5-point scale. Follow-up was made at 1-month and 3-month. RESULTS: Not statistically significant differences emerged between the three groups at baseline. Mean ejaculatory latency time at the 3-month follow-up in G1, G2 and G3 was 3.7+/-1.3, 3.4+/-1.5, 5.6+/-1.7 (p<0.001). Mean satisfaction score was at the 3-month follow-up in G1: 2.8+/-1.4, in G2: 2.9+/-1.8, and G3: 3.7+/-1.5 (p<0.002). None of the patients withdrew from the study because of these adverse events. CONCLUSIONS: This study demonstrates that Tadalafil used daily has a role on treatment in lifelong PE. This action is valid when combined strategically to the synergistic action of lidocaine spray applied before intercourse increasing significantly the mean IELT.