苯氟雷司

苯氟雷司
臨床資料
商品名（英語：Drug nomenclature）	Mediator
AHFS/Drugs.com	國際藥品名稱
給藥途徑	口服
ATC碼	A10BX06 (WHO) ;
藥物動力學數據
排泄途徑	腎
識別資訊
	IUPAC命名法 (RS)-2-({1-[3-(trifluoromethyl)phenyl]propan- 2-yl}amino)ethyl benzoate; ;
CAS號	23602-78-0
PubChem CID	2318;
DrugBank	DB09022 ;
ChemSpider	2228 ;
UNII	403FO0NQG3;
KEGG	D07192 ;
ChEMBL	ChEMBL400599 ;
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID5048471 ;
ECHA InfoCard	100.041.601
化學資訊
化學式	C19H20F3NO2
摩爾質量	351.37 g·mol−1
3D模型（JSmol（英語：JSmol））	交互式圖像;
手性	Racemic mixture
	SMILES FC(F)(F)c1cccc(c1)CC(NCCOC(=O)c2ccccc2)C;
	InChI InChI=1S/C19H20F3NO2/c1-14(12-15-6-5-9-17(13-15)19(20,21)22)23-10-11-25-18(24)16-7-3-2-4-8-16/h2-9,13-14,23H,10-12H2,1H3 ; Key:CJAVTWRYCDNHSM-UHFFFAOYSA-N ;

苯氟雷司（英語：Benfluorex），商品名為Mediator，是一種在結構上與氟苯丙胺（一種苯丙胺替代物，也叫芬氟拉明）相關的厭食劑和降血脂劑。對於控制不佳的2型糖尿病患者，它可以改善血糖控制並降低胰島素抵抗。^[1]^[2]

它於1976年至2009年間上市，據信已造成500至2,000人死亡。^[3]它獲得專利並由法國製藥公司施維雅製造。然而，施維雅被懷疑其所銷售的苯氟雷司與藥物的醫療特性不符。^[4]

2021年3月29日，法國法院裁定施維雅犯有欺騙和過失殺人罪，對其處以270萬歐元（230萬英鎊）的罰款。^[5]

撤藥

2009年12月18日，歐洲藥品管理局建議在歐盟範圍內停用所有含有苯氟雷司的藥物，因為它們擁有風險，尤其是瓣膜性心臟病（類氟苯丙胺心血管副作用）的風險大於其益處。^[6]因此弗拉雄等人顯示服用苯氟雷司的人患不明原因瓣膜性心臟病的機率更高。^[7]另外，威爾等人研究了超過100萬糖尿病患者，結果表明服用苯氟雷司的患者因瓣膜性心臟病住院率更高。^[8]在法國，該藥物已由施維雅以商品名Mediator作為輔助抗糖尿病藥物銷售。該藥物於1976年至2009年間上市，據信已導致500至2,000人死亡。^[3]這種藥物也在西班牙、葡萄牙和賽普勒斯等國使用。

2021年3月29日，法國法院裁定施維雅犯有欺騙和過失殺人罪，並處以270萬歐元（230萬英鎊）的罰款，因為Mediator與多達2,000人的死亡有關。前高管讓-菲利普·塞塔被判處四年有期徒刑，緩期執行。法國藥品管理局被指控未能對有關該藥物的警告採取足夠快的行動，被罰款303,000歐元。該製藥集團被判欺詐罪名不成立。^[9]

氟苯丙胺是一種相關藥物，在出現心臟瓣膜病、^[10]^[11]肺動脈高壓和心臟纖維化的報道後，於1997年退出市場。這種副作用是由心臟瓣膜5-HT_2B受體上的代謝物去甲氟苯丙胺介導的，^[12]導致三尖瓣上心臟成纖維細胞增殖後心力衰竭的特徵模式。氟苯丙胺和苯氟雷司都形成去甲氟苯丙胺作為代謝物。這種副作用導致氟苯丙胺作為一種厭食藥物在世界範圍內被撤回，隨後苯氟雷司也在歐洲被撤回。

參考資料

^ Moulin P, Andre M, Alawi H, dos Santos LC, Khalid AK, Koev D, et al. Efficacy of benfluorex in combination with sulfonylurea in type 2 diabetic patients: an 18-week, randomized, double-blind study. Diabetes Care. March 2006, 29 (3): 515–20. PMID 16505498. doi:10.2337/diacare.29.03.06.dc05-1439 .
^ Roger P, Auclair J, Drain P. Addition of benfluorex to biguanide improves glycemic control in obese non-insulin-dependent diabetes: a double-blind study versus placebo. Journal of Diabetes and Its Complications. 1999, 13 (2): 62–7. PMID 10432168. doi:10.1016/S1056-8727(98)00004-X.
^ ^3.0 ^3.1 France braced for diabetic drug scandal report. BBC News. 2011-01-11 [2023-02-23]. （原始內容存檔於2019-04-25）.
^ Mullard A. Mediator scandal rocks French medical community. Lancet. March 2011, 377 (9769): 890–2. PMID 21409784. S2CID 5325085. doi:10.1016/s0140-6736(11)60334-6 .
^ Mediator drug: French pharmaceutical firm fined over weight loss pill. BBC News. 29 March 2021 [2023-02-23]. （原始內容存檔於2023-03-06）.
^ European Medicines Agency recommends withdrawal of benfluorex from the market in European Union (PDF). European Medicines Agency. 2009-12-18 [2015-01-12]. （原始內容 (PDF)存檔於2009-12-22）.
^ Frachon I, Etienne Y, Jobic Y, Le Gal G, Humbert M, Leroyer C. Lexchin J , 編. Benfluorex and unexplained valvular heart disease: a case-control study. PLOS ONE. April 2010, 5 (4): e10128. Bibcode:2010PLoSO...510128F. PMC 2853566 . PMID 20405030. doi:10.1371/journal.pone.0010128 .
^ Weill A, Païta M, Tuppin P, Fagot JP, Neumann A, Simon D, et al. Benfluorex and valvular heart disease: a cohort study of a million people with diabetes mellitus. Pharmacoepidemiology and Drug Safety. December 2010, 19 (12): 1256–62. PMID 20945504. S2CID 15979457. doi:10.1002/pds.2044 .
^ French pharma firm found guilty over medical scandal in which up to 2,000 died. TheGuardian.com. 29 March 2021 [2023-02-23]. （原始內容存檔於2023-03-08）.
^ Connolly HM, Crary JL, McGoon MD, Hensrud DD, Edwards BS, Edwards WD, Schaff HV. Valvular heart disease associated with fenfluramine-phentermine. The New England Journal of Medicine. August 1997, 337 (9): 581–8. PMID 9271479. doi:10.1056/NEJM199708283370901.
^ Weissman NJ. Appetite suppressants and valvular heart disease. The American Journal of the Medical Sciences. April 2001, 321 (4): 285–91. PMID 11307869. S2CID 46466276. doi:10.1097/00000441-200104000-00008.
^ Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL. Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation. December 2000, 102 (23): 2836–41. PMID 11104741. doi:10.1161/01.cir.102.23.2836 .

[1] Moulin P, Andre M, Alawi H, dos Santos LC, Khalid AK, Koev D, et al. Efficacy of benfluorex in combination with sulfonylurea in type 2 diabetic patients: an 18-week, randomized, double-blind study. Diabetes Care. March 2006, 29 (3): 515–20. PMID 16505498. doi:10.2337/diacare.29.03.06.dc05-1439 .

[2] Roger P, Auclair J, Drain P. Addition of benfluorex to biguanide improves glycemic control in obese non-insulin-dependent diabetes: a double-blind study versus placebo. Journal of Diabetes and Its Complications. 1999, 13 (2): 62–7. PMID 10432168. doi:10.1016/S1056-8727(98)00004-X.

[BCC2011-3] 3.0 ^3.1 France braced for diabetic drug scandal report. BBC News. 2011-01-11 [2023-02-23]. （原始內容存檔於2019-04-25）.

[4] Mullard A. Mediator scandal rocks French medical community. Lancet. March 2011, 377 (9769): 890–2. PMID 21409784. S2CID 5325085. doi:10.1016/s0140-6736(11)60334-6 .

[5] Mediator drug: French pharmaceutical firm fined over weight loss pill. BBC News. 29 March 2021 [2023-02-23]. （原始內容存檔於2023-03-06）.

[6] European Medicines Agency recommends withdrawal of benfluorex from the market in European Union (PDF). European Medicines Agency. 2009-12-18 [2015-01-12]. （原始內容 (PDF)存檔於2009-12-22）.

[7] Frachon I, Etienne Y, Jobic Y, Le Gal G, Humbert M, Leroyer C. Lexchin J , 編. Benfluorex and unexplained valvular heart disease: a case-control study. PLOS ONE. April 2010, 5 (4): e10128. Bibcode:2010PLoSO...510128F. PMC 2853566 . PMID 20405030. doi:10.1371/journal.pone.0010128 .

[8] Weill A, Païta M, Tuppin P, Fagot JP, Neumann A, Simon D, et al. Benfluorex and valvular heart disease: a cohort study of a million people with diabetes mellitus. Pharmacoepidemiology and Drug Safety. December 2010, 19 (12): 1256–62. PMID 20945504. S2CID 15979457. doi:10.1002/pds.2044 .

[9] French pharma firm found guilty over medical scandal in which up to 2,000 died. TheGuardian.com. 29 March 2021 [2023-02-23]. （原始內容存檔於2023-03-08）.

[pmid9271479-10] Connolly HM, Crary JL, McGoon MD, Hensrud DD, Edwards BS, Edwards WD, Schaff HV. Valvular heart disease associated with fenfluramine-phentermine. The New England Journal of Medicine. August 1997, 337 (9): 581–8. PMID 9271479. doi:10.1056/NEJM199708283370901.

[pmid11307869-11] Weissman NJ. Appetite suppressants and valvular heart disease. The American Journal of the Medical Sciences. April 2001, 321 (4): 285–91. PMID 11307869. S2CID 46466276. doi:10.1097/00000441-200104000-00008.

[12] Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL. Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation. December 2000, 102 (23): 2836–41. PMID 11104741. doi:10.1161/01.cir.102.23.2836 .

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