慢性便秘治疗新药-Elobixibat
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摘要
Elobixibat(商品名:Goofice)是全球首款获得国家和地区批准上市的胆汁酸转运抑制药物,可在回肠内与胆汁酸转运体特异性结合,阻断胆汁酸转运的过程,促进胆汁酸转运到结肠内发挥促进分泌和胃肠蠕动的作用,从而达到治疗慢性便秘的目的。临床研究证实,与传统的肠道促分泌药和肠道促动力药相比,Elobixibat可以有效降低排便的硬度并增加排便次数,提高排便流畅性的同时较少引起腹部痉挛或疼痛,因此,该药于2018年4月19日正式在日本上市。本文对Elobixibat的作用机制、药动学、临床评价、药物相互作用和安全性等方面进行综述,为临床治疗和深入研究提供参考。
Elobixibat(trade name:Goofice) is the world′s first biliary acid transport inhibitor approved by countries and regions.It can specifically bind with bile acid transporters in the ileum,block the process of bile acid transport,promote bile acid transport to the colon to promote secretion and gastrointestinal peristalsis,so as to achieve the goal of curing chronic constipation.Clinical studies have confirmed that Elobixibat can effectively reduce the hardness of defecation and increase the frequency of defecation,improve the fluidity of defecation and reduce abdominal spasm or pain,compared with traditional intestinal secretion-stimulating drugs and intestinal motility-stimulating drugs.Therefore,the drug was marketed on April 19th,2018 in Japan.This article reviews Elobixibat's mechanism of action,pharmacokinetics,clinical evaluation,drug interaction and safety,and provides reference for clinical treatment and in-depth research.
Elobixibat(trade name:Goofice) is the world′s first biliary acid transport inhibitor approved by countries and regions.It can specifically bind with bile acid transporters in the ileum,block the process of bile acid transport,promote bile acid transport to the colon to promote secretion and gastrointestinal peristalsis,so as to achieve the goal of curing chronic constipation.Clinical studies have confirmed that Elobixibat can effectively reduce the hardness of defecation and increase the frequency of defecation,improve the fluidity of defecation and reduce abdominal spasm or pain,compared with traditional intestinal secretion-stimulating drugs and intestinal motility-stimulating drugs.Therefore,the drug was marketed on April 19th,2018 in Japan.This article reviews Elobixibat's mechanism of action,pharmacokinetics,clinical evaluation,drug interaction and safety,and provides reference for clinical treatment and in-depth research.
引文
[1] Nakajima A,Seki M,Taniguchi S.Determining an optimal clinical dose of elobixibat,a novel inhibitor of the ileal bile acid transporter,in Japanese patients with chronic constipation:a phase II,multicenter,double-blind,placebo-controlled randomized clinical trial[J].J Gastroenterol,2018,53(4):525-534.
[2] Bharucha AE,Pemberton JH,Locke GR.American Gastroenterological Association technical review on constipation[J].Gastroenterology,2013,144(1):218-238.
[3] Hong KS,Jung KW,Lee TH,et al.Current issues on the treatment of chronic constipation [J].Korean J Gastroenterol,2014,64(3):148-153.
[4] Dinning PG,Di LC.Colonic dysmotility in constipation[J].Best Pract Res Clin Gastroenterol,2011,25(1):89-101.
[5] Nusrat S,Miner PB.New pharmacological treatment options for irritable bowel syndrome with constipation[J].Expert Opin Emerg Drugs,2015,20(4):625-636.
[6] Acosta A,Camilleri M.Elobixibat and its potential role in chronic idiopathic constipation[J].Ther Adv Gastroenterol,2014,7(4):167-175.
[7] Alrefai WA,Gill RK.Bile acid transporters:structure,function,regulation and pathophysiological implications[J].Pharm Res,2007,24(10):1803-1823.
[8] Appleby RN,Walters JR.The role of bile acids in functional GIdisorders[J].Neurogastroenterol Motil,2014,26(8):1057-1069.
[9] Jiang C,Xu Q,Wen X,et al.Current developments in pharmacological therapeutics for chronic constipation[J].Acta Pharm Sin B,2015,5(4):300-309.
[10] Bajor A,Gillberg PG,Abrahamsson H.Bile acids:short and long term effects in the intestine[J].Scand J Gastroenterol,2010,45(6):645-664.
[11] Gillberg P,Dahlstrom M,Starke I,et al.The IBAT inhibition by A3309-a potential mechanism for the treatment of constipation[J].Gastroenterol Clin North Am,2010,138:S224.
[12] Gillberg PG,Dahlstr?m M,Starke I,et al.The IBAT inhibition by A3309-a potential mechanism for the treatment of constipation[J].Gastroenterology,2010,5(Suppl 1):224.
[13] Simren M,Bajor A,Gillberg PG,et al.Randomised clinical trial:the ileal bile acid transporter inhibitor A3309 vs placebo in patients with chronic idiopathic constipation-a double-blind study[J].Aliment Pharmacol Ther,2011,34:41-50.
[14] Tosetti C,Stanghellini V,Corinaldesi R.Therome II criteria for patients with functional gastroduodenal disorders[J].J Clin Gastroenterol,2003,37(1):92-93.
[15] G?lman C,Arvidsson I,Angelin B,et al.Monitoring hepatic cholesterol 7-hydroxylase activity by assay of the stable bile acid intermediate 7-hydroxy-4-cholesten-3-one in peripheral blood[J].J Lipid Res,2003,44:859-865.
[16] Wong BS,Camilleri M,McKinzie S,et al.Effects of A3309,an ileal bile acid transporter inhibitor,on colonic transit and symptoms in females with functional constipation[J].Am J Gastroenterol,2011,106(12):2154-2164.
[17] Longstreth GF,Thompson WG,Chey WD,et al.Functional bowel disorders[J].Gastroenterology,2006,130(5):1480-1491.
[18] Chey WD,Camilleri M,Chang L,et al.A randomized placebo-controlled phase IIb trial of a3309,a bile acid transporter inhibitor,for chronic idiopathic constipation[J].Am J Gastroenterol,2011,106(10):1803-1812.
[19] 26 week efficacy and safety trial for patients with chronic idiopathic constipation[EB/OL].[2015-10-20].https://clinicaltrials.gov/ct2/show/NCT01827592.
[20] Bharucha A,Dorn S,Lembo A,et al.(2013a)American Gastroenterological Association medical position statement on constipation[J].Gastroenterology,2013,144:211-217.
[21] Bharucha A,Pemberton J,Locke G.(2013b)American Gastroenterological Association technical review on constipation[J].Gastroenterology,2013,144:218-238.
[22] Nullens S,Nelsen T,Camilleri M,et al.Regional colon transit in patients with dys-synergic defaecation or slow transit in patients with constipation[J].Gut,2012,61(8):1132-1139.
[2] Bharucha AE,Pemberton JH,Locke GR.American Gastroenterological Association technical review on constipation[J].Gastroenterology,2013,144(1):218-238.
[3] Hong KS,Jung KW,Lee TH,et al.Current issues on the treatment of chronic constipation [J].Korean J Gastroenterol,2014,64(3):148-153.
[4] Dinning PG,Di LC.Colonic dysmotility in constipation[J].Best Pract Res Clin Gastroenterol,2011,25(1):89-101.
[5] Nusrat S,Miner PB.New pharmacological treatment options for irritable bowel syndrome with constipation[J].Expert Opin Emerg Drugs,2015,20(4):625-636.
[6] Acosta A,Camilleri M.Elobixibat and its potential role in chronic idiopathic constipation[J].Ther Adv Gastroenterol,2014,7(4):167-175.
[7] Alrefai WA,Gill RK.Bile acid transporters:structure,function,regulation and pathophysiological implications[J].Pharm Res,2007,24(10):1803-1823.
[8] Appleby RN,Walters JR.The role of bile acids in functional GIdisorders[J].Neurogastroenterol Motil,2014,26(8):1057-1069.
[9] Jiang C,Xu Q,Wen X,et al.Current developments in pharmacological therapeutics for chronic constipation[J].Acta Pharm Sin B,2015,5(4):300-309.
[10] Bajor A,Gillberg PG,Abrahamsson H.Bile acids:short and long term effects in the intestine[J].Scand J Gastroenterol,2010,45(6):645-664.
[11] Gillberg P,Dahlstrom M,Starke I,et al.The IBAT inhibition by A3309-a potential mechanism for the treatment of constipation[J].Gastroenterol Clin North Am,2010,138:S224.
[12] Gillberg PG,Dahlstr?m M,Starke I,et al.The IBAT inhibition by A3309-a potential mechanism for the treatment of constipation[J].Gastroenterology,2010,5(Suppl 1):224.
[13] Simren M,Bajor A,Gillberg PG,et al.Randomised clinical trial:the ileal bile acid transporter inhibitor A3309 vs placebo in patients with chronic idiopathic constipation-a double-blind study[J].Aliment Pharmacol Ther,2011,34:41-50.
[14] Tosetti C,Stanghellini V,Corinaldesi R.Therome II criteria for patients with functional gastroduodenal disorders[J].J Clin Gastroenterol,2003,37(1):92-93.
[15] G?lman C,Arvidsson I,Angelin B,et al.Monitoring hepatic cholesterol 7-hydroxylase activity by assay of the stable bile acid intermediate 7-hydroxy-4-cholesten-3-one in peripheral blood[J].J Lipid Res,2003,44:859-865.
[16] Wong BS,Camilleri M,McKinzie S,et al.Effects of A3309,an ileal bile acid transporter inhibitor,on colonic transit and symptoms in females with functional constipation[J].Am J Gastroenterol,2011,106(12):2154-2164.
[17] Longstreth GF,Thompson WG,Chey WD,et al.Functional bowel disorders[J].Gastroenterology,2006,130(5):1480-1491.
[18] Chey WD,Camilleri M,Chang L,et al.A randomized placebo-controlled phase IIb trial of a3309,a bile acid transporter inhibitor,for chronic idiopathic constipation[J].Am J Gastroenterol,2011,106(10):1803-1812.
[19] 26 week efficacy and safety trial for patients with chronic idiopathic constipation[EB/OL].[2015-10-20].https://clinicaltrials.gov/ct2/show/NCT01827592.
[20] Bharucha A,Dorn S,Lembo A,et al.(2013a)American Gastroenterological Association medical position statement on constipation[J].Gastroenterology,2013,144:211-217.
[21] Bharucha A,Pemberton J,Locke G.(2013b)American Gastroenterological Association technical review on constipation[J].Gastroenterology,2013,144:218-238.
[22] Nullens S,Nelsen T,Camilleri M,et al.Regional colon transit in patients with dys-synergic defaecation or slow transit in patients with constipation[J].Gut,2012,61(8):1132-1139.