Cazzola Mario, Calzetta Luigino, Rogliani Paola, Matera Maria Gabriella
Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome 'Tor Vergata', Rome, Italy.
Unit of Respiratory Disease and Lung Function, Department of Medicine and Surgery, University of Parma, Parma, Italy.
Expert Rev Clin Pharmacol. 2024 Dec;17(12):1149-1161. doi: 10.1080/17512433.2024.2438187. Epub 2024 Dec 5.
The therapeutic implications of phosphodiesterase (PDE) inhibitors have attracted interest because PDEs are regarded as an intracellular target to be exploited for therapeutic advancements in the treatment of COPD. At present, the only approved approach for the treatment of COPD with PDE inhibitors is the use of an oral PDE4 inhibitor. However, this treatment is not widely employed, primarily due to the narrow therapeutic index associated with oral PDE4 inhibitors, which significantly limits the tolerable dose. The inhalation route represents a viable alternative to the oral route for improving the therapeutic index of PDE4 inhibitors.
The development of inhaled PDE4 inhibitors, with a focus on tanimilast and ensifentrine, the latter of which is a dual PDE3/PDE4 inhibitor.
The inhalation route offers several advantages regarding the delivery of PDE inhibitors for the management of COPD. Tanimilast and ensifentrine have been shown to improve lung function, reduce exacerbations and enhance quality of life in COPD patients. However, it has not yet been determined which type of COPD patient might benefit more from inhaled PDE4 inhibitors, and it remains unclear whether concomitant inhibition of PDE3 and PDE4 confers a significant benefit compared to blocking PDE4 alone in COPD.
磷酸二酯酶(PDE)抑制剂的治疗意义引起了人们的关注,因为PDE被视为细胞内靶点,有望用于慢性阻塞性肺疾病(COPD)治疗的进展。目前,使用PDE抑制剂治疗COPD唯一获批的方法是使用口服PDE4抑制剂。然而,这种治疗方法并未广泛应用,主要是因为口服PDE4抑制剂的治疗指数较窄,这显著限制了可耐受剂量。吸入途径是提高PDE4抑制剂治疗指数的一种可行替代口服途径的方法。
吸入性PDE4抑制剂的研发,重点是他尼司特和恩西芬特林,后者是一种双重PDE3/PDE4抑制剂。
吸入途径在为COPD管理递送PDE抑制剂方面具有多个优势。他尼司特和恩西芬特林已被证明可改善COPD患者的肺功能、减少急性加重并提高生活质量。然而,目前尚未确定哪种类型的COPD患者可能从吸入性PDE4抑制剂中获益更多,并且与单独阻断PDE4相比,同时抑制PDE3和PDE4在COPD中是否具有显著益处仍不明确。