Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, Illinois, USA.
Clin Ther. 2011 Aug;33(8):993-1004. doi: 10.1016/j.clinthera.2011.06.008. Epub 2011 Jul 16.
Tadalafil is a phosphodiesterase-5 (PDE-5) inhibitor that was approved by the US Food and Drug Administration (FDA) in 2009 for the treatment of pulmonary arterial hypertension (PAH).
The purpose of this review is to evaluate the pharmacology, pharmacokinetic properties, clinical efficacy, adverse effects, drug interactions, and dosage and administration of tadalafil in patients with PAH.
A literature search of MEDLINE and International Pharmaceutical Abstracts (1960 through September 5, 2010) was conducted with the search terms tadalafil, pulmonary arterial hypertension, and phosphodiesterase-5 inhibitor. Data found from orignial research and case series published in English were screened for relevancy to pharmacology, pharmacokinetics, clinical efficacy and safety, and tolerability. Relevant articles from the bibliographies of the identified published articles were also obtained. Unpublished data and posters were obtained from the manufacturer of tadalafil and the FDA Web site.
By selectively inhibiting PDE-5, tadalafil causes nitric oxide-mediated vasodilation in the pulmonary vasculature. Tadalafil has a greater affinity (10,000-fold) for PDE-5 compared with the other PDE inhibitors and has a t(½) of 17.5 hours. In a controlled clinical study in patients with PAH, patients receiving tadalafil in a total daily dose of 40 mg had significant improvements in their 6-minute walk distance (33 m from baseline) and time to clinical worsening compared with those receiving placebo (both, P < 0.05). Tadalafil had adverse effects similar to placebo, with headache being the most commonly reported (42%).
In the small number of studies available, tadalafil was effective and well tolerated when used to treat patients with PAH. Compared with placebo, tadalafil was associated with significant improvements in exercise capacity and reduced time to clinical worsening (68% relative risk reduction; P = 0.038). There is limited evidence comparing tadalafil with sildenafil and vardenafil, and the studies are limited by short treatment durations.
他达拉非是一种磷酸二酯酶-5（PDE-5）抑制剂，于 2009 年经美国食品和药物管理局（FDA）批准用于治疗肺动脉高压（PAH）。
本综述旨在评估他达拉非在 PAH 患者中的药理学、药代动力学特性、临床疗效、不良反应、药物相互作用、剂量和给药方法。
对 MEDLINE 和国际药学文摘（1960 年至 2010 年 9 月 5 日）进行文献检索，检索词为他达拉非、肺动脉高压和磷酸二酯酶-5 抑制剂。从英文原始研究和病例系列出版物中筛选出与药理学、药代动力学、临床疗效和安全性以及耐受性相关的数据。还从已发表文章的参考文献中获得了相关文章。从他达拉非制造商和 FDA 网站获得了未发表的数据和海报。
通过选择性抑制 PDE-5，他达拉非引起肺血管中一氧化氮介导的血管舒张。他达拉非对 PDE-5 的亲和力（10000 倍）高于其他 PDE 抑制剂，t（½）为 17.5 小时。在一项对 PAH 患者的对照临床试验中，接受他达拉非总日剂量 40mg 的患者与接受安慰剂的患者相比，6 分钟步行距离（从基线增加 33m）和临床恶化时间均有显著改善（均为 P<0.05）。他达拉非的不良反应与安慰剂相似，最常见的是头痛（42%）。
在现有的少量研究中，他达拉非在治疗 PAH 患者时有效且耐受性良好。与安慰剂相比，他达拉非可显著改善运动能力并减少临床恶化时间（相对风险降低 68%；P=0.038）。与西地那非和伐地那非比较的证据有限，且研究受治疗持续时间短的限制。
