Sildenafil - A review of its use in erectile dysfunction
Sildenafil - A review of its use in erectile dysfunction
复制标题
DOI：
10.2165/00003495-199957060-00015
复制
发表时间：
1999-06-01
期刊：
影响因子：
11.5
通讯作者：
Markham, A
中科院分区：
文献类型：
--
作者：
Langtry, HD;Markham, A
西地那非是一种口服治疗勃起功能障碍的广泛原因。通过选择性抑制5型磷酸二酯酶，它使海绵体平滑肌放松，在性刺激时增强勃起。西地那非可短暂降低血压，但同时使用西地那非和有机硝酸盐时可能出现更明显的低血压；这种组合是禁忌的。西地那非吸收迅速，给药1小时内血药浓度与剂量成正比，消除半衰期为3 ~ 5小时。剂量通常为50mg，在性活动前1小时服用，每天不超过一次。当需要每日一次时，最大剂量为100mg，老年患者和肝肾损害或接受细胞色素P450酶CYP3A4抑制剂（如利托那韦、沙奎那韦、酮康唑、红霉素或西咪替丁）的患者可使用较小剂量（如25mg）。在固定剂量或滴定剂量的试验中，超过3000名患有有机勃起功能障碍（如糖尿病或脊髓损伤）、心因性或混合原因勃起功能障碍的患者接受了西地那非5至100mg或安慰剂。西地那非与勃起频率、硬度和持续时间的剂量相关改善以及患者实现和维持足以成功性交的勃起的能力相关。在滴定剂量试验中，最常见的有效剂量为50或100mg，尽管在一些患者中较低剂量有效，但西地那非在所有测试原因的勃起功能障碍中明显比安慰剂更有效，西地那非的疗效不受患者年龄（bb60或小于或等于65岁）或降压或抗抑郁药物的影响，该药对严重勃起功能障碍患者有效。在长期（1年）的研究中，疗效保持不变，西地那非似乎也改善了患者及其性伴侣的生活质量。与西地那非相关的常见不良事件是短暂的、轻度或中度的，包括头痛、脸红、消化不良、鼻塞和视力异常。在长期（2年）研究中，耐受性保持不变。临床试验中未发生严重的西地那非相关不良事件；上市后监测中发现的心血管事件通常发生在有其他已知危险因素的患者中。结论：西地那非是治疗男性勃起功能障碍的有效口服药物。它在改善勃起和允许成功的插入性行为方面明显优于安慰剂。尽管西地那非在疾病管理中的地位仍在兴起，并且存在使用禁忌症，但如果初步阳性报告得到证实，西地那非将成为治疗勃起功能障碍的首选一线药物。
Sildenafil is an oral therapy for erectile dysfunction of a broad range of causes. By selectively inhibiting phosphodiesterase type 5, it allows corpus' cavernosum smooth muscle to relax, potentiating erections during sexual stimulation. Blood pressure is reduced transiently by sildenafil, but more marked hypotension may occur during concurrent administration of sildenafil and organic nitrates; this combination is contraindicated.Sildenafil is rapidly absorbed, with dose-proportional peak plasma concentrations within 1 hour of administration, The elimination half-life is 3 to 5 hours. Dosages usually begin at 50mg taken when needed approximate to 1 hour before sexual activity no more than once daily. The maximum dose is 100mg when needed once daily and lower doses (e,g, 25mg) may be used in elderly patients and those with hepatic or renal impairment or receiving cytochrome P450 enzyme CYP3A4 inhibitors, such as ritonavir, saquinavir, ketoconazole, erythromycin or cimetidine.More than 3000 patients with erectile dysfunction of organic (e,g, diabetes or spinal cord injury), psychogenic or mixed origin received sildenafil 5 to 100mg or placebo in fixed- or titrated-dose trials, Sildenafil was associated with dose-related improvements in the frequency, hardness and duration of erections and in patients' abilities to achieve and maintain erections adequate for successful sexual intercourse. In titrated-dose trials, the most commonly effective doses were 50 or 100mg, although lower doses were effective in some patients, Sildenafil was significantly more effective than placebo in erectile dysfunction of all tested causes,The efficacy of sildenafil was not affected by patient age (> or less than or equal to 65 years) or by antihypertensive or antidepressant medications, The drug was effective in patients with severe erectile dysfunction, Efficacy was maintained in long term (l-year) studies, Sildenafil also appears to improve the quality of life of both patients and their sexual partners. Common adverse events associated with sildenafil were transient and mild or moderate and included headache, flushing, dyspepsia, nasal congestion and abnormal vision. Tolerability was maintained in long term (II year) studies. No serious sildenafil-related adverse events occurred in clinical trials; cardiovascular events seen in postmarketing surveillance generally occurred in patients with other known risk factors.Conclusions: Sildenafil is an effective oral treatment in men with erectile dysfunction. It was significantly superior to placebo in improving erections and allowing successful penetrative sexual intercourse. Although its place in disease management is still emerging and there are contraindications to its use, if preliminary positive reports are confirmed, sildenafil will be the pre-eminent first-line therapy for erectile dysfunction.