Oklahoma Foundation for Digestive Research, 1813 Coventry Lane, Oklahoma City, OK, 73120, USA.
Drug Saf. 2019 May;42(5):603-615. doi: 10.1007/s40264-018-0781-9.
Plecanatide, a uroguanylin analog, activates the guanylate cyclase C receptors in the epithelial lining of the gastrointestinal tract in a pH-dependent fashion initiating (1) the conversion of intracellular guanosine triphosphate to cyclic guanosine monophosphate, which increases the activity of the cystic fibrosis transmembrane conductance regulator to increase chloride and bicarbonate secretion into the intestinal lumen and (2) a decrease in activity of the sodium-hydrogen ion exchanger. The resulting ionic shifts cause an increase in lumenal fluid to facilitate digestion. Plecanatide has been approved by the FDA for use in chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation. This manuscript is a critical assessment of the therapeutic efficacy and potential risks associated with the use of plecanatide in CIC. The discussion of CIC as a clinical and investigative disorder focuses on the importance of this problem as well and the difficulties involved in clinical management and scholarly investigation of a symptom arising from multiple pathophysiologic mechanisms. Clinical data from studies of recently approved drugs for CIC are utilized to construct a platform for thoughtful understanding of CIC and of how changes in investigation guidelines influence the interpretation of study data and guide symptom management. Plecanatide is a safe and effective medication for the management of adults with CIC.
普卡那肽是一种尿鸟苷素类似物，以 pH 依赖性方式激活胃肠道上皮衬里中的鸟苷酸环化酶 C 受体，从而启动：(1) 细胞内三磷酸鸟苷转化为环鸟苷单磷酸，增加囊性纤维化跨膜电导调节因子的活性，从而增加氯离子和碳酸氢根离子向肠腔分泌；(2) 减少钠-氢离子交换器的活性。由此引起的离子转移导致管腔液体增加，有助于消化。普卡那肽已获 FDA 批准用于慢性特发性便秘（CIC）和伴有便秘的肠易激综合征的治疗。本文对 CIC 患者使用普卡那肽的治疗效果和潜在风险进行了批判性评估。CIC 作为一种临床和研究障碍的讨论，重点强调了这一问题的重要性，以及在临床管理和对源于多种病理生理机制的症状进行学术研究方面所面临的困难。利用最近批准用于 CIC 的药物的研究临床数据，为深入了解 CIC 以及研究指南的变化如何影响对研究数据的解释和指导症状管理提供了一个平台。普卡那肽是治疗成人 CIC 的一种安全有效的药物。
