2316

112 / 6. 19~ 6. 25

藥聞

Gefapixant拮抗P2X2/3受體止咳新藥

 

 

 


◎文/藥學生吳承軒、高雄記者毛志民


全球約有10%至12%的人患有慢性咳嗽,若小孩持續四週以上的咳嗽,成人持續八週以上咳嗽定義為慢性咳嗽。


Gefapixant是非鴉片類、選擇性P2X3及P2X2/3受體拮抗劑,Gefapixant的臨床早期研究中,曾對骨關節疼痛(膝關節)、間質性膀胱炎/膀胱疼痛和哮喘患者進行臨床II期研究,但這些研究都已中斷;再對阻塞性睡眠呼吸暫停進行臨床I期研究,特發性肺纖維化伴頑固性咳嗽和子宮內膜異位疼痛進行了II期研究卻都沒有進展,僅在治療難治性或不明原因之慢性咳嗽有所突破,2022年元月獲得日本藥政單位「醫藥品醫療機器綜合機構」(Pharmaceuticals and Medical Devices Agency,PMDA)核准上市,美國及歐盟藥政單位正新藥審查中。


P2X受體為ATP調控三聚體離子通道(ATP-gated trimeric ion channels),具有P2X1-7七種亞型;咳嗽由Aδ-fibres及C-fibres組成迷走神經調控,其中C-fibres可以被ATP活化P2X3受體而引發咳嗽。


慢性咳嗽常見共病包括:氣喘、非氣喘性嗜酸性支氣管炎(nonasthmatic eosinophilic bronchitis)、慢性阻塞性肺病、胃食道逆流、大腸激躁症及肥胖等;慢性咳嗽的成因複雜、診斷不易,現行治療多以這些共病著手。然而,就算控制得宜,許多患者卻仍慢性咳嗽不止,國內醫師常以Codeine、Dextromethorphan等藥物治療,但也埋下藥物濫用、呼吸抑制等隱患。


Gefapixant於納入1360位受試者的臨床第三期試驗顯示,相較安慰組可顯著降低24小時咳嗽頻率;合併兩個雙盲研究共計超過2,000名參與者的研究顯示,每天兩次服用Gefapixant 45mg,咳嗽頻率降低了18.5%,然各種族最適劑量的調整仍需要深入探究。由系統性回顧文獻可知常見不良反應有味覺障礙或喪失、頭痛、咳嗽、上呼吸道或泌尿道感染,但統計並無顯著差異,且停藥後便可緩解,預期此全新機轉止咳藥會是治療慢性咳嗽的新選擇。


(本文藥學生為大仁科技大學藥學系臨床組)


參考資料:


1.Abu-Zaid, A., et al., Safety and efficacy of gefapixant, a novel drug for the treatment of chronic cough: A systematic review and meta-analysis of randomized controlled trials. Ann Thorac Med, 2021. 16(2): p. 127-140.
2.Steven EW., Kai S. Causes and epidemiology of subacute and chronic cough in adults. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on October 27, 2022.)
3.Cui, W.W., et al., P2X3-selective mechanism of Gefapixant, a drug candidate for the treatment of refractory chronic cough. Comput Struct Biotechnol J, 2022. 20: p. 1642-1653.
4.Ford, A.P., et al., The discovery and development of gefapixant. Auton Neurosci, 2021. 235: p. 102859.
5.Markham, A., Gefapixant: First Approval. Drugs, 2022. 82(6): p. 691-695.
6.McGarvey, L.P., et al., Efficacy and safety of gefapixant, a P2X(3) receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. Lancet, 2022. 399(10328): p. 909-923.
7.Morice, A.H., et al., ERS guidelines on the diagnosis and treatment of chronic cough in adults and children. Eur Respir J, 2020. 55(1).
8.Muccino, D. and S. Green, Update on the clinical development of gefapixant, a P2X3 receptor antagonist for the treatment of refractory chronic cough. Pulm Pharmacol Ther, 2019. 56: p. 75-78.
9.Smith, J.A., et al., Improvements in Objective and Subjective Measures of Chronic Cough with Gefapixant: A Pooled Phase 3 Efficacy Analysis of Predefined Subgroups. Lung, 2022.
 

 

 

回首頁