他达拉非治疗勃起功能障碍的安全性研究进展

勃起功能障碍(erectile dysfunction,ED)是中老年人的常见疾病。他达拉非自2002年10月开始用于治疗ED,其疗效确切,安全性高,因此越来越多的患者选择他达拉非来治疗ED。目前对他达拉非的作用机制、药代动力学、疗效、安全性等方面已经有了较多的基础及临床研究资料。本文就他达拉非治疗ED的安全性做一综述,以求该药物在临床上得到更安全的使用,为临床医生选择使用该类药物提供参考。     

Tadalafil in the treatment of erectile dysfunction; an overview of the clinical evidence

Prevalence and severity of erectile dysfunction (ED) increase with aging and are often associated with illnesses, like diabetes mellitus, heart disease, and hypertension, pathologically characterized by endothelial dysfunction and whose prevalence increases with age. The assumption that ED is mainly a neurovascular disease is supported by the evidence that specific phosphodiesterase type 5 (PDE5) inhibition produces an efficient erection in a wide range of ages and conditions. The availability of specific PDE5 inhibitors has enabled the development of effective treatment strategies, in this contest, tadalafil may be considered as the least “typical” PDE5 inhibitor. In clinical trials, tadalafil significantly enhanced, in patients of different ages, all efficacy outcomes across disease etiologies and severities. With an effectiveness lasting up to 36h, tadalafil allows patients to choose when to have sexual activities without the need to time it, showing positive feedback in terms of quality of life related to the treatment. Headache and dyspepsia were the most frequent side-effects of tadalafil, followed by back pain, nasal congestion, myalgia, and flushing, but the impact that long time action could have on effectiveness and safety is not yet entirely defined. The aim of this article is to critically review the available evidence from the tadalafil clinical research program and give the physician a rational approach for intervention in the treatment of ED and related diseases.     

他达拉非在阴茎勃起功能障碍中的疗效评价

他达拉非是一种口服治疗勃起功能障碍的PDE-5抑制剂药物,其作用时间可以维持到服用药物后36h,具有良好的有效性和安全性,并且可以改善由其它疾病导致的勃起功能障碍,本文对他达拉非治疗阴茎勃起功能障碍的疗效进行综述。     

The effect of cardiovascular morbidity on clinical response provided by tadalafil in patients with erectile dysfunction

We aimed to investigate the association between erectile dysfunction and severity of cardiovascular morbidity and to assess clinical responses to tadalafil of patients in different cardiovascular risk groups. Between November 2019 and August 2020, a total of 258 male patients aged 45–70 years with ED were included. They were divided into three groups according to the Framingham risk score: low-risk (n: 86, 33.3%), intermediate-risk (n: 103, 39.9%) and high-risk (n: 69, 26.8%). At admission, all domains of the International Index of Erectile Function score were worse in high-risk group compared to other risk groups (p < .001). After a 12-week follow-up, a more significant improvement was observed in all domains of erectile function in all risk groups, but high-risk group had lower sexual scores (p < .001). The lowest rate for complete responsiveness to tadalafil was observed in the high-risk group (37.7%). The rate of failure in complete responsiveness was found to be 4.127 times greater with higher Framingham score and 3.102 times greater with higher erectile dysfunction severity at admission. Our preliminary findings show that more severe sexual disorders are observed in high-risk patients with cardiovascular morbidity. Individualised treatment may be important in high-risk group since they may benefit less from tadalafil, and failure in complete responsiveness can be more common in this group.     

Seminal vesicles of infertile patients with male accessory gland infection: ultrasound evaluation after prolonged treatment with tadalafil,a selective phosphodiesterase‐5 inhibitor

The aim of this study was to investigate possible ultrasound seminal vesicle (SV) changes in infertile patients with ‘hypertrophic‐congestive’ (HCUF) or ‘fibro‐sclerotic’ (FSUF) ultrasound form of male accessory gland infection (MAGI) after prolonged administration of tadalafil (TAD), a selective phosphodiesterase‐5 inhibitor. Forty infertile patients with HCUF and 40 patients with FSUF and erectile dysfunction were selected and arbitrarily divided into two groups, who were prescribed TAD 5 mg daily for 3 months, the first 20 consecutive patients with HCUF (group A1) or FSUF (group A2) or placebo, the second 20 consecutive patients with HCUF (group B1) or FSUF (group B2). All patients underwent scrotal and prostate‐vesicular transrectal ultrasound evaluation and semen analysis (WHO, 2010) before and after treatment. Group A1 patients showed a significant reduction in fundus/body ratio and higher pre‐ and post‐ejaculatory body SV antero‐posterior diameter difference compared with the other three groups. These patients showed also a significant increase in SV ejection fraction and a significant improvement in the total sperm count, progressive motility, seminal levels of fructose and ejaculate volume. These results suggest that infertile patients with HCUF had an improvement in SV ultrasound features suggestive of chronic inflammation after daily treatment with low doses of TAD.     

中成药中非法添加物N-苄基他达拉非的结构确证

目的 鉴定中成药中一种新型他达拉非类似物。方法 采用HPLC-DAD初筛和制备液相色谱仪对中成药中非法添加物进行分离和纯化，采用高分辨质谱确定其精确分子量和结构碎片，结合碳谱和氢谱，最终确定该添加物的结构。结果 该添加物为N-苄基他达拉非。结论 N-苄基他达拉非的化学结构已有文献报道，但作为一种非法的中成药添加物首次被检出。     

Tadalafil: 15 years' journey in male erectile dysfunction and beyond

Tadalafil, Cialis, Eli Lilly & Co./ICOS, (6R,12aR)-6-(1,3-benzodioxol-5-yl)-2-methyl-2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6] pyrido[3,4-b]indole-1,4-dione, was first discovered in 2003. It was reported to have high diastereospecificity for phosphodiesterase 5 (PDE5) inhibitions. The cis-(6R, 12aR) enantiomer is the most active enantiomer. Tadalafil showed PDE5 inhibition with IC₅₀ = 5 nM. It possesses high selectivity for PDE5 versus PDE1-4 and PDE6. Tadalafil is more selective to PDE5 against PDE6 whereas sildenafil, another commercially available PDE5 inhibitor shows similar potencies to inhibit PDE5 and PDE6. Tadalafil is used for the treatment of male erectile dysfunction (MED), prostatic benign hyperplasia (PBH) signs and symptoms, and pulmonary arterial hypertension (PAH). Adcirca, another name for tadalafil, is used to treat PAH and improve exercise capacity. Recent clinical studies suggest the use of tadalafil for nonurological applications, including circulatory disorders (ischemia injury, myocardial infarction, cardiac hypertrophy, cardiomyopathy, heart failure, and stroke), neurodegenerative disorders, and cognitive impairment conditions. This review discusses tadalafil and its analogues reported in the past 15 years. It discusses synthetic pathways, structural activity relationships, existing and future pharmacological indications of tadalafil and its analogues. This work can help medicinal chemists developing novel PDE5 inhibitors with wider therapeutic indications.     

按时口服他达拉非治疗按需口服西地那非治疗无效的勃起功能障碍(附15例报告)

目的:总结他达拉非治疗西地那非治疗无效的勃起功能障碍患者的诊疗经验。方法:回顾总结2010年9月至2012年3月15例按需口服西地那非治疗无效的勃起功能障碍患者的病例资料。结果:15例按需口服西地那非治疗无效的勃起功能障碍患者中,11例治疗后勃起功能改善明显,4例改善不明显,有效率73.3%。治疗前后IIEF-5评分比较有显著性差异(P<0.05),疗效满意。4例患者出现不良反应,其中轻微头痛2例,颜面潮红1例,1例出现轻微的腰背痛,均为一过性,继续用药后减轻或消失。结论:按时口服他达拉非是治疗按需口服西地那非治疗无效的勃起功能障碍患者的安全有效方法。