{"id":621,"date":"2025-07-21T20:55:22","date_gmt":"2025-07-21T12:55:22","guid":{"rendered":"http:\/\/m-middle.com\/?p=621"},"modified":"2025-07-21T20:55:23","modified_gmt":"2025-07-21T12:55:23","slug":"%e6%81%a9%e8%a5%bf%e5%9c%b0%e5%b9%b3idhifa%ef%bc%8cenasidenib-%e4%bb%b7%e6%a0%bc-%e8%af%b4%e6%98%8e%e4%b9%a6-%e4%ba%a7%e5%93%81%e4%bf%a1%e6%81%af","status":"publish","type":"post","link":"http:\/\/m-middle.com\/index.php\/2025\/07\/21\/%e6%81%a9%e8%a5%bf%e5%9c%b0%e5%b9%b3idhifa%ef%bc%8cenasidenib-%e4%bb%b7%e6%a0%bc-%e8%af%b4%e6%98%8e%e4%b9%a6-%e4%ba%a7%e5%93%81%e4%bf%a1%e6%81%af\/","title":{"rendered":"\u6069\u897f\u5730\u5e73(Idhifa\uff0cenasidenib)-\u4ef7\u683c-\u8bf4\u660e\u4e66-\u4ea7\u54c1\u4fe1\u606f"},"content":{"rendered":"\n
\"\"<\/figure>
\n

\u6069\u897f\u5730\u5e73(Idhifa\uff0cenasidenib)FDA\u5b98\u65b9\u8bf4\u660e\u4e66
\u6279\u51c6\u65e5\u671f\uff1a2017\u5e748\u67081\u65e5\uff1b\u516c\u53f8\uff1aCelgene Corporation
\u4e3a\u6cbb\u7597\uff1a\u6025\u6027\u9ad3\u6027\u767d\u8840\u75c5<\/p>\n\n\n\n

\u9002\u5e94\u8bc1\u548c\u7528\u9014
IDHIFA\u662f\u4e00\u79cd\u5f02\u67e0\u6aac\u9178\u8131\u6c22\u9176-2\u6291\u5236\u5242\u9002\u7528\u4e3a\u6210\u5e74\u60a3\u8005\u6709\u590d\u53d1\u6216\u96be\u6cbb\u6027\u6025\u6027\u9ad3\u6027\u767d\u8840\u75c5(AML)\u7684\u6cbb\u7597\u5f53\u88abFDA-\u6279\u51c6\u7684\u6d4b\u8bd5\u68c0\u6d4b\u5230\u6709\u4e00\u4e2a\u5f02\u67e0\u6aac\u9178\u8131\u6c22\u9176-2(IDH2)\u7a81\u53d8\u3002(1.1).<\/p>\n<\/div><\/div>\n\n\n\n

\u5242\u91cf\u548c\u7ed9\u836f\u65b9\u6cd5
100 mg\u53e3\u670d\u6bcf\u59291\u6b21\u76f4\u81f3\u75be\u75c5\u8fdb\u5c55\u6216\u4e0d\u53ef\u63a5\u53d7\u6bd2\u6027\u3002(2.2).
\u5242\u578b\u548c\u89c4\u683c
\u7247\uff1a50 mg\u6216100 mg(3).
\u7981\u5fcc\u8bc1
\u65e0(4).
\u8b66\u544a\u548c\u6ce8\u610f\u4e8b\u9879
\u80da\u80ce-\u80ce\u513f\u6bd2\u6027\uff1aIDHIFA\u53ef\u80fd\u81f4\u80ce\u513f\u5371\u5bb3\u5f53\u7ed9\u4e88\u4e00\u4f4d\u598a\u5a20\u5987\u5973\u3002\u5fe0\u544a\u5bf9\u80ce\u513f\u6f5c\u5728\u98ce\u9669\u3002(5.2\uff0c8.1\uff0c8.3).
\u4e0d\u826f\u53cd\u5e94
\u6700\u5e38\u89c1\u4e0d\u826f\u53cd\u5e94(\u226520%)\u5305\u62ec\u6076\u5fc3\uff0c\u5455\u5410\uff0c\u8179\u6cfb\uff0c\u5347\u9ad8\u7684\u80c6\u7ea2\u7d20\uff0c\u548c\u98df\u6b32\u51cf\u4f4e(6.1).
\u62a5\u544a\u6000\u7591\u4e0d\u826f\u53cd\u5e94\uff0c\u8054\u7cfbCelgene Corporation\u7535\u8bdd1-888-423-5436\u6216FDA\u7535\u8bdd1-800-FDA-1088\u6216www.fda.gov\/medwatch.
\u5728\u7279\u6b8a\u4eba\u7fa4\u4e2d\u4f7f\u7528
\u54fa\u4e73\uff1a\u5efa\u8bae\u5987\u5973\u4e0d\u8981\u54fa\u4e73\u5582\u517b\u3002(8.2).
\u5b8c\u6574\u5904\u65b9\u8d44\u6599<\/p>\n\n\n\n

1 \u9002\u5e94\u8bc1\u548c\u7528\u9014
1.1 \u6025\u6027\u9ad3\u6027\u767d\u8840\u75c5
IDHIFA\u662f\u9002\u7528\u4e3a\u5f53\u88ab\u4e00\u79cdFDA-\u6279\u51c6\u7684\u6d4b\u8bd5\u68c0\u6d4b\u5230\u6709\u4e00\u4e2a\u5f02\u67e0\u6aac\u9178\u8131\u6c22\u9176-2(IDH2)\u7a81\u53d8\u6709\u590d\u53d1\u6216\u96be\u6cbb\u6027\u6025\u6027\u9ad3\u6027\u767d\u8840\u75c5(AML)\u6210\u5e74\u60a3\u8005\u7684\u6cbb\u7597\u3002
2 \u5242\u91cf\u548c\u7ed9\u836f\u65b9\u6cd5
2.1 \u60a3\u8005\u9009\u62e9
\u4e3aAML\u7528IDHIF\u7684\u6cbb\u7597\u9009\u62e9\u60a3\u8005\u6839\u636e\u5728\u8840\u6216\u9aa8\u9ad3\u4e2dIDH2\u7a81\u53d8\u7684\u5b58\u5728[\u89c1\u9002\u5e94\u8bc1\u548c\u7528\u9014(1.1)\u548c\u4e34\u5e8a\u7814\u7a76(14.1)]\u3002\u5728http:\/\/www.fda.gov\/CompanionDiagnostics. \u53ef\u5f97\u4e3a\u5230\u5728AML\u4e2dIDH2\u7a81\u53d8\u7684\u68c0\u6d4b\u7684FDA-\u6279\u51c6\u7684\u6d4b\u8bd5\u7684\u8d44\u6599
2.2 \u63a8\u8350\u5242\u91cf
IDHIFA\u7684\u63a8\u8350\u5f00\u59cb\u5242\u91cf\u4e3a100 mg\u53e3\u670d\u6bcf\u59291\u6b21\u6709\u6216\u65e0\u98df\u7269\u76f4\u81f3\u75be\u75c5\u8fdb\u5c55\u6216\u4e0d\u53ef\u63a5\u53d7\u6bd2\u6027\u3002\u5bf9\u65e0\u75be\u75c5\u8fdb\u5c55\u6216\u4e0d\u53ef\u63a5\u53d7\u6bd2\u6027\u60a3\u8005\uff0c\u6cbb\u7597\u5171\u6700\u5c0f6\u4e2a\u6708\u5141\u8bb8\u5bf9\u4e34\u5e8a\u53cd\u5e94\u65f6\u95f4\u3002
\u4e0d\u8981\u5206\u88c2\u6216\u538b\u788eIDHIFA\u7247\u3002\u7ed9\u4e88IDHIFA\u7247\u53e3\u670d\u6bcf\u5929\u7ea6\u76f8\u540c\u65f6\u95f4\u3002\u5982\u4e00\u5242IDHIFA\u81f3\u6b63\u5e38\u65f6\u95f4\u8868\u88ab\u5455\u5410\uff0c\u7f3a\u5931\uff0c\u6216\u4e0d\u80fd\u5728\u5bfb\u5e38\u65f6\u95f4\u670d\u7528\uff0c\u5c3d\u53ef\u80fd\u5728\u76f8\u540c\u5929\u9a6c\u4e0a\u7ed9\u4e88\u5242\u91cf\uff0c\u548c\u8fd4\u56de\u4e0b\u4e00\u5929\u6b63\u5e38\u65f6\u95f4\u8868\u3002
2.3 \u5bf9\u6bd2\u6027\u76d1\u89c6\u548c\u5242\u91cf\u4fee\u9970
IDHIFA\u7684\u5f00\u59cb\u524d\u8bc4\u4f30\u8840\u7ec6\u80de\u8ba1\u6570\u548c\u8840\u6db2\u5316\u5b66\u5bf9\u767d\u7ec6\u80de\u589e\u591a\u548c\u80bf\u7624\u6eb6\u89e3\u7efc\u5408\u8bc1 \u548c\u76d1\u89c6\u5728\u4e00\u4e2a\u6700\u5c0f\u6bcf2\u5468\u5171\u81f3\u5c11\u6cbb\u7597\u671f\u95f4\u81f3\u5c11\u59343\u4e2a\u6708\u3002\u53ca\u65f6\u5904\u7406\u4efb\u4f55\u5f02\u5e38[\u89c1\u4e0d\u826f\u53cd\u5e94(6.1)]\u3002
\u5bf9\u6bd2\u6027\u4e2d\u65ad\u7ed9\u836f\u6216\u51cf\u4f4e\u5242\u91cf\u3002\u5bf9\u5242\u91cf\u4fee\u9970\u6307\u5bfc\u89c1\u88681\u3002<\/p>\n\n\n\n

3 \u5242\u578b\u548c\u89c4\u683c
IDHIFA\u53ef\u5f97\u5230\u4ee5\u4e0b\u7247\u5f3a\u5ea6\uff1a
\u25cf 50-mg\u7247\uff1a\u6de1\u9ec4\u8272\u81f3\u9ec4\u8272\u692d\u5706\u5f62\u8584\u819c\u5305\u8863\u7247\u4e00\u4fa7\u51f9\u9677\u201dENA\u201c\u548c\u53e6\u4e00\u4fa7\u4e0a\u201c50\u201d\u3002
\u25cf 100-mg\u7247\uff1a\u8c08\u9ec4\u8272\u81f3\u9ec4\u8272\u80f6\u56ca\u5f62\u819c\u5305\u8863\u7247\u4e00\u4fa7\u51f9\u9677\u201dENA\u201c\u548c\u53e6\u4e00\u4fa7\u4e0a\u201c100\u201d\u3002
4 \u7981\u5fcc\u8bc1
\u65e0\u3002
5 \u8b66\u544a\u548c\u6ce8\u610f\u4e8b\u9879
5.1 \u5206\u5316\u7efc\u5408\u75c7
\u5728\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\uff0c14%\u7528IDHIFA\u6cbb\u7597\u60a3\u8005\u7ecf\u53d7\u5206\u5316\u7efc\u5408\u8bc1\uff0c\u5b83\u53ef\u80fd\u662f\u5371\u53ca\u751f\u547d\u6216\u81f4\u547d\u6027\u5982\u4e0d\u6cbb\u7597\u3002\u5206\u5316\u7efc\u5408\u8bc1\u662f\u4f34\u968f\u9aa8\u9ad3\u7ec6\u80de\u8fc5\u901f\u589e\u6b96\u548c\u5206\u5316\u3002\u800c\u5bf9\u5206\u5316\u7efc\u5408\u8bc1\u6ca1\u6709\u8bca\u65ad\u6d4b\u8bd5\uff0c\u7528IDHIFA\u6cbb\u7597\u60a3\u8005\u4e2d\u75c7\u72b6\u5305\u62ec\u6025\u6027\u547c\u5438\u9053\u7a98\u8feb\u7fa4\u4ee3\u8868\u4e3a\u547c\u5438\u56f0\u96be\u548c\/\u6216\u7f3a\u6c27(68%)\u548c\u9700\u8981\u8865\u5145\u6c27(76%)\uff1b\u80ba\u6d78\u6da6(73%)\u548c\u80ba\u79ef\u6db2(45%)\uff1b\u80be\u53d7\u635f(70%)\uff1b\u53d1\u70ed(36%)\uff1b\u6dcb\u5df4\u7ed3\u75c5\u53d8(33%)\uff1b\u9aa8\u75db(27%)\uff1b\u5468\u56f4\u6c34\u80bf\u6709\u8fc5\u901f\u4f53\u91cd\u589e\u91cf(21%)\uff1b\u548c\u5fc3\u5305\u79ef\u6db2(18%)\u3002\u809d\uff0c\u80be\uff0c\u548c\u591a\u5668\u5b98\u529f\u80fd\u4e0d\u5168\u4e5f\u66fd\u88ab\u89c2\u5bdf\u5230\u3002\u5206\u5316\u7efc\u5408\u8bc1\u66fd\u88ab\u89c2\u5bdf\u5230\u6709\u548c\u65e0\u540c\u65f6\u7684\u767d\u7ec6\u80de\u589e\u591a\uff0c\u548c\u65e9\u4e3aDHIFA\u5f00\u59cb\u540e10\u5929\u548c\u5728\u81f35\u4e2a\u6708\u540e\u3002
\u5982\u6000\u7591\u5206\u5316\u7efc\u5408\u8bc1\uff0c\u5f00\u59cb\u53e3\u670d\u6216\u9759\u8109\u76ae\u8d28\u6fc0\u7d20(\u5982\uff0c\u5730\u585e\u7c73\u677e[dexamethasone]10 mg\u6bcf12\u5c0f\u65f6)\u548c\u8840\u6d41\u52a8\u529b\u5b66\u76d1\u89c6\u76f4\u81f3\u6539\u5584\u3002\u4ec5\u5728\u75c7\u72b6\u89e3\u51b3\u540e\u6ef4\u5b9a\u51cf\u4f4e\u76ae\u8d28\u6fc0\u7d20\u3002\u968f\u8fc7\u65e9\u7ec8\u6b62\u76ae\u8d28\u6fc0\u7d20\u6cbb\u7597\u53ef\u80fd\u590d\u53d1\u5206\u5316\u7efc\u5408\u8bc1\u75c7\u72b6\u3002\u5982\u4e25\u91cd\u80ba\u75c7\u72b6\u9700\u8981\u63d2\u7ba1\u6216\u547c\u5438\u673a\u652f\u6301\uff0c\u548c\/\u6216\u76ae\u8d28\u6fc0\u7d20\u7684\u5f00\u59cb\u540e\u80be\u529f\u80fd\u4e0d\u5168\u6301\u7eed\u5171\u8d85\u8fc748\u5c0f\u65f6\uff0c\u4e2d\u65adIDHIFA\u76f4\u81f3\u4f53\u5f81\u548c\u75c7\u72b6\u662f\u4e0d\u518d\u4e25\u91cd[\u89c1\u5242\u91cf\u548c\u7ed9\u836f\u65b9\u6cd5(2.3)]\u3002\u63a8\u8350\u4f4f\u9662\u4e3a\u5bc6\u5207\u89c2\u5bdf\u548c\u76d1\u89c6\u6709\u80ba\u548c\/\u6216\u80be\u8868\u73b0\u7684\u60a3\u8005\u3002
5.2 \u80da\u80ce-\u80ce\u513f\u6bd2\u6027
\u6839\u636e\u52a8\u7269\u80da\u80ce-\u80ce\u513f\u6bd2\u6027\u7814\u7a76\uff0cIDHIFA\u53ef\u81f4\u80da\u80ce-\u80ce\u513f\u5371\u5bb3\u5f53\u7ed9\u4e88\u81f3\u4e00\u4f4d\u598a\u5a20\u5987\u5973\u3002\u5728\u52a8\u7269\u80da\u80ce-\u80ce\u513f\u6bd2\u6027\u7814\u7a76\uff0cenasidenib\u81f4\u80da\u80ce-\u80ce\u513f\u6bd2\u6027\u5f00\u59cb\u57280.1\u500d\u7a33\u6001\u4e34\u5e8a\u66b4\u9732\u6839\u636e\u6d53\u5ea6\u65f6\u95f4\u66f2\u7ebf\u4e0b\u9762\u79ef(AUC)\u5728\u63a8\u8350\u4eba\u5242\u91cf\u3002\u5fe0\u544a\u751f\u6b96\u6f5c\u80fd\u5973\u6027\u7528IDHIFA\u6cbb\u7597\u671f\u95f4\u548c\u672b\u6b21\u5242\u91cfIDHIFA\u540e\u5171\u81f3\u5c111\u4e2a\u6708\u4f7f\u7528\u6709\u6548\u907f\u5b55\u3002\u5fe0\u544a\u6709\u751f\u6b96\u6f5c\u80fd\u5973\u6027\u4f34\u4fa3\u7537\u6027\u4f7f\u7528\u6709\u6548\u907f\u5b55\u7528IDHIFA\u6cbb\u7597\u671f\u95f4\u548c\u672b\u6b21\u5242\u91cfIDHIFA\u540e\u5171\u81f3\u5c111\u4e2a\u6708\u4f7f\u7528\u6709\u6548\u907f\u5b55\u3002\u598a\u5a20\u5987\u5973\uff0c\u60a3\u8005\u6210\u4e3a\u598a\u5a20\u5f53\u63a5\u53d7IDHIFA\uff0c\u6216\u6709\u598a\u5a20\u5973\u6027\u4f34\u4fa3\u7537\u6027\u5e94\u88ab\u5fe0\u544a\u5bf9\u80ce\u513f\u6f5c\u5728\u98ce\u9669[\u89c1\u5728\u7279\u6b8a\u4eba\u7fa4\u4e2d\u4f7f\u7528(8.1\uff0c8.3)]\u3002
6 \u4e0d\u826f\u53cd\u5e94
\u5728\u8bf4\u660e\u4e66\u4e2d\u4efb\u4f55\u5904\u63cf\u8ff0\u4ee5\u4e0b\u4e25\u91cd\u7684\u4e0d\u826f\u53cd\u5e94\uff1a
\u25cf \u5206\u5316\u7efc\u5408\u8bc1[\u89c1\u8b66\u544a\u548c\u6ce8\u610f\u4e8b\u9879(5.1)]
6.1 \u4e34\u5e8a\u8bd5\u9a8c\u7ecf\u9a8c
\u56e0\u4e3a\u4e34\u5e8a\u8bd5\u9a8c\u662f\u5728\u5e7f\u6cdb\u4e0d\u540c\u60c5\u51b5\u4e0b\u8fdb\u884c\u7684\uff0c\u4e34\u5e8a\u8bd5\u9a8c\u89c2\u5bdf\u5230\u4e0d\u826f\u53cd\u5e94\u7387\u4e0d\u80fd\u4e0e\u53e6\u4e00\u79cd\u836f\u4e34\u5e8a\u8bd5\u9a8c\u53d1\u751f\u7387\u76f4\u63a5\u6bd4\u8f83\u800c\u4e14\u53ef\u80fd\u4e0d\u53cd\u6620\u5b9e\u8df5\u4e2d\u89c2\u5bdf\u5230\u7684\u53d1\u751f\u7387\u3002
\u5355\u5242\u91cf-\u836f\u7269IDHIFA\u7684\u5b89\u5168\u6027\u8bc4\u4ef7\u662f\u6839\u636e214\u4f8b\u60a3\u8005\u6709\u590d\u53d1\u6216\u96be\u6cbb\u6027AML\u60a3\u8005\u88ab\u81f3\u63a5\u53d7100 mg\u6bcf\u5929[\u89c1\u4e34\u5e8a\u7814\u7a76(14.1)]\u3002\u5bf9IDHIFA\u66b4\u9732\u4e2d\u4f4d\u65f6\u95f4\u4e3a4.3\u4e2a\u6708(\u8303\u56f40.3\u81f323.6)\u3002\u89c2\u5bdf\u5230\u7528IDHIFA 30-\u5929\u548c60-\u5929\u6b7b\u4ea1\u7387\u5206\u522b\u4e3a4.2%(9\/214)\u548c11.7%(25\/214)\u3002
\u4efb\u4f55\u7ea7\u522b\u7684\u6700\u5e38\u89c1\u4e0d\u826f\u53cd\u5e94(\u226520%)\u4e3a\u6076\u5fc3\uff0c\u5455\u5410\uff0c\u8179\u6cfb\uff0c\u5347\u9ad8\u7684\u80c6\u7ea2\u7d20\u548c\u98df\u6b32\u51cf\u4f4e\u3002
\u572877.1%\u7684\u60a3\u8005\u88ab\u62a5\u9053\u7684\u4e25\u91cd\u4e0d\u826f\u53cd\u5e94\u3002\u6700\u9891\u6570\u4e25\u91cd\u7684\u4e0d\u826f\u53cd\u5e94(\u22652%)\u4e3a\u767d\u7ec6\u80de\u589e\u591a(10%)\uff0c\u8179\u6cfb(6%)\uff0c\u6076\u5fc3(5%)\uff0c\u5455\u5410(3%)\uff0c\u98df\u6b32\u51cf\u4f4e(3%)\uff0c\u80bf\u7624\u6eb6\u89e3\u7efc\u5408\u8bc1(5%)\uff0c\u548c\u5206\u5316\u7efc\u5408\u8bc1(8%)\u3002\u5206\u5316\u7efc\u5408\u8bc1\u4e8b\u4ef6\u7279\u5f81\u4e3a\u4e25\u91cd\u7684\u5305\u62ec\u53d1\u70ed\uff0c\u6025\u6027\u80be\u8870\u7aed\uff0c\u7f3a\u6c27\uff0c\u547c\u5438\u8870\u7aed\uff0c\u548c\u591a\u5668\u5b98\u8870\u7aed\u3002
\u603b\u4e4b\uff0c92\/214\u60a3\u8005(43%)\u9700\u8981\u4e00\u4e2a\u5242\u91cf\u4e2d\u65ad\u7531\u4e8e\u4e00\u4e2a\u4e0d\u826f\u53cd\u5e94\uff1b\u6700\u5e38\u89c1\u4e0d\u826f\u53cd\u5e94\u5bfc\u81f4\u5242\u91cf\u4e2d\u65ad\u4e3a\u5206\u5316\u7efc\u5408\u8bc1(4%)\u548c\u767d\u7ec6\u80de\u589e\u591a(3%)\u300210\/214\u60a3\u8005(5%)\u9700\u8981\u5242\u91cf\u51cf\u4f4e\u7531\u4e8e\u4e00\u4e2a\u4e0d\u826f\u53cd\u5e94\uff1b\u65e0\u4e0d\u826f\u53cd\u5e94\u9700\u8981\u5242\u91cf\u51cf\u4f4e\u5728\u591a\u4e8e2\u60a3\u8005\u300236\/214\u60a3\u8005(17%)\u6c38\u4e45\u5730\u7ec8\u6b62IDHIFA\u7531\u4e8e\u4e00\u4e2a\u4e0d\u826f\u53cd\u5e94\uff1b\u6c38\u4e45\u7ec8\u6b62\u4e3a\u767d\u7ec6\u80de\u589e\u591a(1%)\u3002
\u88682\u4e2d\u663e\u793a\u8bd5\u9a8c\u4e2d\u62a5\u9053\u7684\u4e0d\u826f\u53cd\u5e94\u3002<\/p>\n\n\n\n

\u5176\u4ed6\u4e34\u5e8a\u4e0a\u663e\u8457\u4e0d\u826f\u53cd\u5e94\u53d1\u751f\u5728\u226410\u7684\u60a3\u8005\u5305\u62ec\uff1a
\u547c\u5438\uff0c\u80f8\uff0c\u548c\u7eb5\u9694\u75be\u60a3\uff1a\u80ba\u6c34\u80bf\uff0c\u6025\u6027\u547c\u5438\u9053\u7a98\u8feb\u7fa4\u7efc\u5408\u8bc1\u3002
\u5728\u88683\u4e2d\u663e\u793a\u5728\u5728\u6709\u590d\u53d1\u6216\u96be\u6cbb\u6027AML\u60a3\u8005\u89c2\u5bdf\u5230\u9009\u5b9a\u7684\u57fa\u7ebf\u540e\u5b9e\u9a8c\u5ba4\u6570\u503c\u4e2d\u53d8\u5316\u3002<\/p>\n\n\n\n

\u5347\u9ad8\u7684\u80c6\u7ea2\u7d20
IDHIFA\u901a\u8fc7UGT1A1\u7684\u6291\u5236\u4f5c\u7528\u53ef\u80fd\u5e72\u6270\u80c6\u7ea2\u7d20\u4ee3\u8c22[\u89c1\u4e34\u5e8a\u836f\u7406\u5b66(12.3)]\u300237%\u60a3\u8005(80\/214)\u80c6\u7ea2\u7d20\u5347\u9ad8\u22652 x ULN\u81f3\u5c11\u4e00\u6b21\u3002\u90a3\u4e9b\u7ecf\u5386\u603b\u80c6\u7ea2\u7d20\u5347\u9ad8 \u22652 x ULN\u60a3\u8005\u4e2d\uff0c35%\u6709\u5347\u9ad8\u5728\u6cbb\u7597\u7684\u5934\u4e00\u4e2a\u6708\u5185\uff0c\u548c89%\u6ca1\u6709\u540c\u65f6\u8f6c\u6c28\u9176\u7684\u5347\u9ad8\u6216\u5176\u4ed6\u4e0d\u826f\u4e8b\u4ef6\u4e0e\u809d\u75be\u60a3\u76f8\u5173\u3002\u65e0\u60a3\u8005\u9700\u8981\u4e3a\u9ad8\u80c6\u7ea2\u7d20\u8840\u75c7\u5242\u91cf\u51cf\u4f4e\uff1b\u6cbb\u7597\u88ab\u4e2d\u65ad\u57283.7%\u60a3\u8005\uff0c\u5171\u4e00\u4e2a\u4e2d\u4f4d\u65706\u5929\u3002\u4e09\u4f8b\u60a3\u8005(1.4%) \u6c38\u4e45\u7ec8\u6b62IDHIFA\u7531\u4e8e\u9ad8\u80c6\u7ea2\u7d20\u8840\u75c7\u3002
\u975e\u611f\u67d3\u6027\u767d\u7ec6\u80de\u589e\u591a
IDHIFA\u53ef\u80fd\u8bf1\u5bfc\u9aa8\u9ad3\u589e\u6b96\u5bfc\u81f4\u4e00\u4e2a\u767d\u7ec6\u80de\u8ba1\u6570\u8fc5\u901f\u589e\u52a0\u3002
\u80bf\u7624\u6eb6\u89e3\u7efc\u5408\u75c7
IDHIFA\u53ef\u80fd\u8bf1\u5bfc\u9aa8\u9ad3\u589e\u6b96\u5bfc\u81f4\u5728\u80bf\u7624\u7ec6\u80de\u4e2d\u4e00\u4e2a\u8fc5\u901f\u51cf\u4f4e\u5b83\u53ef\u80fd\u5177\u6709\u5bf9\u80bf\u7624\u6eb6\u89e3\u7efc\u5408\u75c7\u4e00\u4e2a\u98ce\u9669\u3002
8 \u5728\u7279\u6b8a\u4eba\u7fa4\u4e2d\u4f7f\u7528
8.1 \u598a\u5a20
\u98ce\u9669\u603b\u7ed3
\u6839\u636e\u52a8\u7269\u80da\u80ce-\u80ce\u513f\u6bd2\u6027\u7814\u7a76\uff0cIDHIFA\u53ef\u80fd\u81f4\u80ce\u513f\u5371\u5bb3\u5f53\u7ed9\u4e88\u81f3\u4e00\u4f4d\u598a\u5a20\u5987\u5973\u3002\u5bf9IDHIFA\u5728\u598a\u5a20\u5987\u5973\u4f7f\u7528\u6ca1\u6709\u53ef\u5f97\u5230\u6570\u636e\u544a\u77e5\u4e00\u4e2a\u91cd\u5927\u51fa\u751f\u7f3a\u9677\u548c\u6d41\u4ea7\u7684\u836f\u7269\u5173\u8054\u98ce\u9669\u3002\u5728\u52a8\u7269\u80da\u80ce-\u80ce\u513f\u6bd2\u6027\u7814\u7a76\uff0cenasidenib\u7684\u53e3\u670d\u7ed9\u4e88\u81f3\u598a\u5a20\u5927\u9f20\u548c\u5154\u5668\u5b98\u5f62\u6210\u671f\u95f4\u88ab\u4f34\u968f\u80da\u80ce-\u80ce\u513f\u6b7b\u4ea1\u7387\u548c\u6539\u53d8\u5bf9\u751f\u957f\u5f00\u59cb\u57280.1\u500d\u7a33\u6001\u4e34\u5e8a\u66b4\u9732\u6839\u636e\u5728\u63a8\u8350\u4eba\u5242\u91cf\u65f6AUC (\u89c1\u6570\u636e)\u3002\u5982\u8be5\u836f\u5728\u598a\u5a20\u671f\u95f4\u4f7f\u7528\uff0c\u6216\u5982\u60a3\u8005\u5f53\u670d\u7528\u8be5\u836f\u65f6\u6210\u4e3a\u598a\u5a20\uff0c\u5fe0\u544a\u60a3\u8005\u5bf9\u80ce\u513f\u6f5c\u5728\u98ce\u9669\u3002
\u5728\u598a\u5a20\u53d1\u751f\u4e0d\u826f\u7ed3\u5c40\u4e0d\u7ba1\u6bcd\u4eb2\u7684\u5065\u5eb7\u6216\u836f\u7269\u7684\u4f7f\u7528\u3002\u4e0d\u77e5\u9053\u5bf9\u9002\u5e94\u8bc1\u4eba\u7fa4\u91cd\u5927\u51fa\u751f\u7f3a\u9677\u548c\u6d41\u4ea7\u7684\u80cc\u666f\u98ce\u9669\u3002\u5728\u7f8e\u56fd\u4e00\u822c\u4eba\u7fa4\u4e2d\uff0c\u91cd\u5927\u51fa\u751f\u7f3a\u9677\u548c\u5728\u4e34\u5e8a\u4e0a\u8ba4\u53ef\u598a\u5a20\u4e2d\u6d41\u4ea7\u7684\u4f30\u7b97\u80cc\u666f\u98ce\u9669\u5206\u522b\u4e3a2%-4%\u548c15%-20%\u3002
\u6570\u636e
\u52a8\u7269\u6570\u636e
\u5668\u5b98\u5f62\u6210\u671f\u95f4(\u598a\u5a20\u59296-17) \u6bcf\u59292\u6b21\u7ed9\u4e88Enasidenib\u81f3\u598a\u5a20\u5927\u9f20\u5728\u4e00\u4e2a\u5242\u91cf30 mg\/kg\u662f\u4f34\u968f\u6bcd\u4f53\u6bd2\u6027\u548c\u4e0d\u826f\u80da\u80ce-\u80ce\u513f\u5305\u62ec\u690d\u5165\u540e\u4e22\u5931\uff0c\u518d\u5438\u6536\uff0c\u51cf\u4f4e\u6d3b\u80ce\u513f\uff0c\u8f83\u4f4e\u80ce\u513f\u51fa\u751f\u4f53\u91cd\uff0c\u548c\u9aa8\u9abc\u53d8\u5f02\u3002\u8fd9\u4e9b\u6548\u5e94\u53d1\u751f\u5728\u5927\u9f20\u5728\u63a8\u8350\u4eba\u6bcf\u5929\u5242\u91cf100 mg\/day\u65f6\u4e34\u5e8a\u66b4\u9732\u7ea61.6\u500d\u3002
\u5728\u5668\u5b98\u5f62\u6210\u671f\u95f4(\u598a\u5a20\u59297-19)\u88ab\u6cbb\u7597\u598a\u5a20\u5154\u4e2d\uff0cenasidenib\u662f\u6bcd\u4f53\u5730\u6bd2\u6027\u5728\u5242\u91cf\u7b49\u4e8e5 mg\/kg\/day\u6216\u8f83\u9ad8(\u66b4\u9732\u7ea60.1\u81f30.6\u500d\u5728\u63a8\u8350\u6bcf\u5929\u5242\u91cf\u7a33\u6001\u4e34\u5e8a\u66b4\u9732)\u548c\u81f4\u81ea\u53d1\u6027\u6d41\u4ea7\u57285 mg\/kg\/day(\u66b4\u9732\u7ea60.1\u500d\u5728\u63a8\u8350\u6bcf\u5929\u5242\u91cf\u65f6\u7a33\u6001\u4e34\u5e8a\u66b4\u9732)\u3002
8.2 \u54fa\u4e73
\u98ce\u9669\u603b\u7ed3
\u6ca1\u6709\u5173\u4e8eenasidenib\u6216\u5b83\u7684\u4ee3\u8c22\u7269\u5728\u4eba\u4e73\u6c41\u4e2d\u7684\u5b58\u5728\uff0c\u5bf9\u54fa\u4e73\u5582\u517b\u5a74\u513f\u5f71\u54cd\uff0c\u6216\u5bf9\u4e73\u6c41\u4ea7\u54c1\u751f\u4ea7\u5f71\u54cd\u7684\u6570\u636e\u3002\u56e0\u4e3a\u8bb8\u591a\u836f\u7269\u662f\u6392\u6cc4\u5728\u4eba\u4e73\u6c41\u4e2d\u548c\u56e0\u4e3a\u5bf9\u5728\u54fa\u4e73\u5582\u517b\u5a74\u513f\u4e0d\u826f\u53cd\u5e94\u6f5c\u80fd\uff0c\u7528IDHIFA\u6cbb\u7597\u671f\u95f4\u548c\u672b\u6b21\u5242\u91cf\u540e\u5171\u81f3\u5c111\u4e2a\u6708\u5efa\u8bae\u5987\u5973\u4e0d\u8981\u54fa\u4e73\u5582\u517b\u3002
8.3 \u751f\u6b96\u6f5c\u80fd\u7684\u5973\u6027\u548c\u7537\u6027
\u598a\u5a20\u6d4b\u8bd5
\u6839\u636e\u52a8\u7269\u80da\u80ce-\u80ce\u513f\u6bd2\u6027\u7814\u7a76\uff0c\u5f53\u7ed9\u4e88\u81f3\u4e00\u4f4d\u598a\u5a20\u5987\u5973IDHIFA\u53ef\u80fd\u81f4\u80ce\u513f\u5371\u5bb3[\u89c1\u5728\u7279\u6b8a\u4eba\u7fa4\u4e2d\u4f7f\u7528(8.1)]\u3002
\u5bf9\u751f\u6b96\u6f5c\u80fd\u7684\u5973\u6027\u7528IDHIFA\u6cbb\u7597\u5f00\u59cb\u524d\u5f97\u5230\u4e00\u4e2a\u598a\u5a20\u6d4b\u8bd5\u3002
\u907f\u5b55
\u5973\u6027
\u5efa\u8bae\u751f\u6b96\u6f5c\u80fd\u5973\u6027\u5f53\u63a5\u53d7IDHIFA\u907f\u514d\u6210\u4e3a\u598a\u5a20\u3002\u5efa\u8bae\u751f\u6b96\u6f5c\u80fd\u5973\u6027\u7528IDHIFA\u6cbb\u7597\u671f\u95f4\u548c\u672b\u6b21\u5242\u91cf\u540e\u5171\u81f3\u5c111\u4e2a\u6708\u4f7f\u7528\u6709\u6548\u907f\u5b55\u3002IDHIFA\u7684\u5171\u540c\u7ed9\u836f\u53ef\u80fd\u589e\u52a0\u6216\u51cf\u4f4e\u7ec4\u5408\u6fc0\u7d20\u907f\u5b55\u836f\u7684\u6d53\u5ea6\u3002\u5728\u6b64\u65f6\u4e0d\u77e5\u9053\u8fd9\u4e2a\u6f5c\u5728\u836f\u7269\u76f8\u4e92\u4f5c\u7528\u7684\u4e34\u5e8a\u610f\u4e49\u3002
\u7537\u6027
\u5efa\u8bae\u6709\u751f\u6b96\u6f5c\u80fd\u5973\u6027\u4f34\u4fa3\u7684\u7537\u6027\u7528IDHIFA\u6cbb\u7597\u671f\u95f4\u548cIDHIFA\u7684\u672b\u6b21\u5242\u91cf\u540e\u5171\u81f3\u5c111\u4e2a\u6708\u4f7f\u7528\u6709\u6548\u907f\u5b55\u3002
\u4e0d\u5b55\u4e0d\u80b2
\u6839\u636e\u52a8\u7269\u4e2d\u53d1\u73b0\uff0cIDHIFA\u53ef\u80fd\u5728\u751f\u6b96\u6f5c\u80fd\u5973\u6027\u548c\u7537\u6027\u4e2d\u635f\u5bb3\u751f\u80b2\u529b\u3002\u4e0d\u77e5\u9053\u5bf9\u751f\u80b2\u529b\u7684\u8fd9\u4e9b\u6548\u5e94\u662f\u5426\u662f\u53ef\u9006\u7684[\u89c1\u975e\u4e34\u5e8a\u6bd2\u7406\u5b66(13.1)]\u3002
8.4 \u513f\u7ae5\u4f7f\u7528
\u5c1a\u672a\u786e\u5b9a\u5728\u513f\u7ae5\u60a3\u8005\u5b89\u5168\u6027\u548c\u6709\u6548\u6027\u3002
8.5 \u8001\u5e74\u4eba\u4f7f\u7528
\u5728\u4e34\u5e8a\u7814\u7a76\u4e2d\u65e0\u9700\u5bf9IDHIFA\u6839\u636e\u5e74\u9f84\u5242\u91cf\u8c03\u6574\uff0c214\u60a3\u8005\u4e2d61%\u4e3a\u5e74\u9f8465\u5c81\u6216\u4ee5\u4e0a\uff0c\u800c24% \u4e3a\u8001\u4e8e75\u5c81\u3002\u672a\u89c2\u5bdf\u5230\u60a3\u8005\u5e74\u9f8465\u5c81\u6216\u4ee5\u4e0a\u548c\u8f83\u5e74\u8f7b\u60a3\u8005\u95f4\u5728\u6709\u6548\u6027\u6216\u5b89\u5168\u6027\u4e2d\u603b\u4f53\u5dee\u522b\u3002
11 \u4e00\u822c\u63cf\u8ff0
IDHIFA(enasidenib)\u662f\u4e00\u79cd\u5f02\u67e0\u6aac\u9178\u8131\u6c22\u9176-2(IDH2)\u9176\u7684\u6291\u5236\u5242\u3002Enasidenib\u662f\u53ef\u5f97\u5230\u4f5c\u4e3a\u7532\u78fa\u9178\u76d0\u6709\u5316\u5b66\u540d\uff1a2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}1,3,5-triazin-2-yl)amino]propan-2-ol methanesulfonate.
\u62162-Propanol\uff0c2-methyl-1-[[4-[6-(trifluoromethyl)-2-pyridinyl]-6-[[2-(trifluoromethyl)-4pyridinyl]amino-1,3,5-triazin-2-yl]amino]-\uff0cmethanesulfonate(1:1)\u3002\u5316\u5b66\u7ed3\u6784\u4e3a:<\/p>\n\n\n\n

\u7ecf\u9a8c\u5f0f\u4e3aC19H17F6N7O \u2022<\/p>\n\n\n\n

CH3SO3H(C20H21F6N7O4S)\uff0c\u548c\u5206\u5b50\u91cf\u4e3a569.48 g\/mol\u3002Enasidenib \u662f\u5b9e\u9645\u4e0a\u4e0d\u6eb6\u4e8e\u6c34\u6027\u6eb6\u6db2(\u6eb6\u89e3\u5ea6 \u226474 \u00b5g\/mL)\u8de8\u8d8a\u751f\u7406\u5b66pH\u8303\u56f4(pH 1.2\u548c7.4)\u3002
IDHIFA(enasidenib)\u53ef\u5f97\u5230\u4e3a\u4e00\u4e2a50-mg\u7247(\u7b49\u540c\u4e8e60 mg enasidenib\u7532\u78fa\u9178\u76d0)\u548c\u4e00\u4e2a100-mg\u7247(\u7b49\u540c\u4e8e120 mg enasidenib\u7532\u78fa\u9178\u76d0)\u4e3a\u53e3\u670d\u7ed9\u836f\u3002\u6bcf\u7247\u542b\u65e0\u6d3b\u6027\u6210\u5206\u80f6\u4f53\u4e8c\u6c27\u5316\u7845\uff0c\u7f9f\u4e19\u57fa\u7ea4\u7ef4\u7d20\uff0c\u918b\u9178\u7425\u73c0\u7f9f\u4e19\u7532\u7ea4\u7ef4\u7d20\uff0c\u6c27\u5316\u94c1\u9ec4\uff0c\u786c\u8102\u9178\u9541\uff0c\u5fae\u6676\u7ea4\u7ef4\u7d20\uff0c\u805a\u4e59\u4e8c\u9187\uff0c\u805a\u4e59\u70ef\u9187\uff0c\u786b\u9178\u6708\u6842\u9178\u94a0\uff0c\u7fa7\u7532\u6dc0\u7c89\u94a0\uff0c\u6ed1\u77f3\uff0c\u548c\u4e8c\u6c27\u5316\u949b\u3002
12 \u4e34\u5e8a\u836f\u7406\u5b66
12.1 \u4f5c\u7528\u673a\u5236
Enasidenib\u662f\u4e00\u79cd\u5f02\u67e0\u6aac\u9178\u8131\u6c22\u91762(IDH2)\u9176\u7684\u5c0f\u5206\u5b50\u6291\u5236\u5242\u3002Enasidenib\u9776\u5411\u7a81\u53d8\u4f53IDH2 \u53d8\u5f02\u4f53R140Q\uff0cR172S\uff0c\u548cR172K\u5728\u4f53\u5916\u6bd4\u91ce\u751f\u578b\u9176\u5728\u6d53\u5ea6\u8f83\u4f4e\u7ea640-\u500d\u3002\u7a81\u53d8\u4f53IDH2\u9176\u88abenasidenib\u7684\u6291\u5236\u4f5c\u7528\u5bfc\u81f4\u51cf\u4f4e2-\u7f9f\u620a\u4e8c\u9178[2-hydroxyglutarate(2-HG)]\u6c34\u5e73\u548c\u8bf1\u5bfc\u9aa8\u9ad3\u5206\u5316\u5728\u4f53\u5916\u548c\u5728\u4f53\u5185\u5728IDH2\u7a81\u53d8AML\u7684\u5c0f\u9f20\u79fb\u690d\u7269\u6a21\u578b\uff0c\u5728\u6765\u81ea\u60a3\u8005\u6709\u7a81\u53d8\u7684IDH2AML\u8840\u6837\u54c1\u4e2d\uff0cenasidenib\u51cf\u4f4e2-HG\u6c34\u5e73\uff0c\u51cf\u4f4e\u6bcd\u7ec6\u80de\u8ba1\u6570[blast counts]\u548c\u589e\u52a0\u6210\u719f\u9aa8\u9ad3\u7ec6\u80de\u767e\u5206\u7387\u3002
12.2 \u836f\u6548\u52a8\u529b\u5b66
\u5fc3\u810f\u7535\u751f\u7406\u5b66
\u5728\u4e00\u9879\u5f00\u653e\u7814\u7a76\u5728\u60a3\u8005\u6709\u4e00\u4e2aIDH2\u7a81\u53d8\u6709\u665a\u671f\u8840\u6db2\u5b66\u6076\u6027\u75c5\u8bc4\u4ef7\u7528enasidenib\u5bf9QTc\u5ef6\u957f\u6f5c\u80fd\u3002\u5bf9\u4e00\u4e2a\u5355\u6b21\u5242\u91cf30 mg\u81f3650 mg\u548c\u591a\u6b21\u5242\u91cf100 mg\u6bcf\u5929\u5728\u7a7a\u8179\u72b6\u6001\u6839\u636eQTc\u6570\u636e\uff0c\u7528enasidenib\u6cbb\u7597\u540e\u672a\u89c2\u5bdf\u5230\u5de8\u5927\u5747\u6570\u53d8\u5316\u5728QTc\u95f4\u671f(>20 ms)\u3002
12.3 \u836f\u4ee3\u52a8\u529b\u5b66
\u4e00\u4e2a\u5355\u6b21\u5242\u91cf100 mg\u540e\u8840\u6d46\u5cf0\u6d53\u5ea6(Cmax) \u4e3a1.3 \u00b5g\/mL[%\u53d8\u5f02\u7cfb\u6570(CV%) 56.4]\uff0c\u548c13 \u00b5g\/mL(CV% 46.3)\u5728\u7a33\u6001\u5bf9100 mg\u6bcf\u5929\u3002Enasidenib\u7684\u6d53\u5ea6\u65f6\u95f4\u66f2\u7ebf\u4e0b\u9762\u79ef(AUC)\u589e\u52a0\u5728\u4e00\u4e2a\u5927\u7ea6\u5242\u91cf\u6b63\u6bd4\u4f8b\u65b9\u5f0f\u4ece50 mg(0.5\u500d\u88ab\u6279\u51c6\u7684\u63a8\u8350\u5242\u91cf)\u81f3450 mg(4.5\u500d\u88ab\u6279\u51c6\u7684\u63a8\u8350\u5242\u91cf)\u6bcf\u5929\u7ed9\u836f\u3002\u7a33\u6001\u8840\u6d46\u6c34\u5e73\u88ab\u8fbe\u5230\u572829\u5929\u5185\u6bcf\u59291\u6b21\u7ed9\u836f\u3002\u79ef\u84c4\u662f\u7ea610-\u500d\u5f53\u6bcf\u59291\u6b21\u7ed9\u836f\u3002
\u5438\u6536
100 mg\u53e3\u670d\u5242\u91cf\u7684enasidenib\u540e\u7edd\u5bf9\u751f\u7269\u5229\u7528\u5ea6\u4e3a\u7ea657%\u3002\u4e00\u4e2a\u53e3\u670d\u5355\u5242\u91cf\u540e\u81f3Cmax(Tmax)\u4e2d\u4f4d\u65f6\u95f4\u4e3a4\u5c0f\u65f6\u3002
\u5206\u5e03
Enasidenib\u7684\u5747\u6570\u5206\u5e03\u5bb9\u79ef(Vd)\u4e3a55.8 L(CV% 29)\u3002\u5728\u4f53\u5916Enasidenib\u7684\u4eba\u8840\u6d46\u86cb\u767d\u7ed3\u5408\u4e3a98.5%\u548c\u5b83\u7684\u4ee3\u8c22\u7269AGI-16903\u4e3a96.6%\u3002
Enasidenib\u4e0d\u662f\u5bf9P-\u7cd6\u86cb\u767d\u6216BCRP\u7684\u4e00\u4e2a\u5e95\u7269\uff0c\u800cAGI-16903\u4e3aP\u7cd6\u86cb\u767d\u548cBCRP\u4e24\u8005\u7684\u5e95\u7269\u3002Enasidenib\u548cAGI-16903\u4e0d\u662fMRP2\uff0cOAT1\uff0cOAT3\uff0cOATP1B1\uff0cOATP1B3\uff0c\u548cOCT2\u7684\u5e95\u7269.
\u6d88\u9664
Enasidenib\u6709\u4e00\u4e2a\u672b\u7aef\u534a\u8870\u671f137\u5c0f\u65f6(CV% 41)\u548c\u4e00\u4e2a\u5747\u6570\u603b\u673a\u4f53\u6e05\u9664\u7387(CL\/F)0.74 L\/hour(CV% 71)\u3002
\u4ee3\u8c22
Enasidenib\u5360\u5728\u5faa\u73af\u548cAGI-16903\u653e\u5c04\u6027\u4e3a89%\uff0cN-\u53bb\u70f7\u57fa\u4ee3\u8c22\u7269\uff0c\u4ee3\u886810%\u7684\u5faa\u73af\u653e\u5c04\u6027\u3002
\u5728\u4f53\u5916\u7814\u7a76\u63d0\u793aenasidenib\u7684\u4ee3\u8c22\u662f\u901a\u8fc7\u591a\u4e2aCYP\u9176\u4ecb\u5bfc(\u5982\uff0cCYP1A2\uff0cCYP2B6\uff0cCYP2C8\uff0cCYP2C9\uff0cCYP2C19\uff0cCYP2D6\uff0c\u548cCYP3A4)\uff0c\u4e2a\u901a\u8fc7\u591a\u4e2aUGTs(\u5982\uff0cUGT1A1\uff0cUGT1A3\uff0cUGT1A4\uff0cUGT1A9\uff0cUGT2B7\uff0c\u548cUGT2B15)\u3002\u4ee3\u8c22\u7269AGI-16903\u7684\u8fdb\u4e00\u6b65\u4ee3\u8c22\u4e5f\u662f\u901a\u8fc7\u591a\u4e2a\u9176\u4ecb\u5bfc(\u5982\uff0cCYP1A2\uff0cCYP2C19\uff0cCYP3A4\uff0cUGT1A1\uff0cUGT1A3\uff0c\u548cUGT1A9)\u3002
\u6392\u6cc4
89%\u7684enasidenib\u5728\u7caa\u4e2d\u88ab\u6d88\u9664\u548c11%\u5728\u5c3f\u4e2d\u3002\u672a\u53d8\u5316enasidenib\u7684\u6392\u6cc4\u5360\u5728\u7caa\u4e2d\u653e\u5c04\u6807\u8bb0\u836f\u726934%\u548c\u5728\u5c3f\u4e2d0.4%\u3002
\u7279\u6b8a\u4eba\u7fa4
\u5bf9\u4ee5\u4e0b\u534f\u53d8\u91cf\uff1a\u5e74\u9f84(19\u5c81\u81f3100\u5c81)\uff0c\u79cd\u65cf(\u767d\u79cd\u4eba\uff0c\u9ed1\u79cd\u4eba\uff0c\u6216\u4e9a\u88d4)\uff0c\u8f7b\u5ea6\u809d\u53d7\u635f[\u5b9a\u4e49\u4e3a\u603b\u80c6\u7ea2\u7d20\u2264 \u6b63\u5e38\u4e0a\u9650(ULN)\u548c\u5929\u95e8\u51ac\u8f6c\u6c28\u9176(AST) >ULN\u6216\u603btot\u80c6\u7ea2\u7d201\u81f31.5\u500dULN\u548c\u4efb\u4f55AST]\uff0c\u80be\u53d7\u635f(\u5b9a\u4e49\u4e3a\u808c\u9150\u6e05\u9664\u7387\u226530 mL\/min\u6309Cockcroft-Gault\u516c\u5f0f)\uff0c\u6027\u522b\uff0c\u4f53\u91cd(39 kg\u81f3136 kg)\uff0c\u548c\u4f53\u8868\u9762\u79ef\u672a\u89c2\u5bdf\u5230\u5bf9enasidenib\u7684\u836f\u4ee3\u52a8\u529b\u5b66\u4e34\u5e8a\u610f\u4e49\u7684\u5f71\u54cd\u3002
\u836f\u7269\u76f8\u4e92\u4f5c\u7528\u7814\u7a76
\u5728\u4f53\u5916\u7814\u7a76\u63d0\u793aenasidenib\u6291\u5236CYP1A2\uff0cCYP2B6\uff0cCYP2C8\uff0cCYP2C9\uff0cCYP2C19\uff0cCYP2D6\uff0cCYP3A4\uff0c\u548cUGT1A1\u7684\u6d3b\u6027\u3002Enasidenib\u6291\u5236P-gp\uff0cBCRP\uff0cOAT1\uff0cOATP1B1\uff0cOATP1B3\uff0c\u548cOCT2\uff0c\u4f46\u4e0d\u6291\u5236MRP2\u6216OAT3\u3002Enasidenib\u8bf1\u5bfcCYP2B6\u548cCYP3A4\u3002
\u5728\u4f53\u5916\u7814\u7a76\u63d0\u793a\u4ee3\u8c22\u7269AGI-16903\u6291\u5236CYP1A2\uff0cCYP2B6\uff0cCYP2C8\uff0cCYP2C9\uff0cCYP2C19\uff0c\u548cCYP2D6\u7684\u6d3b\u6027\u3002AGI-16903\u6291\u5236BCRP\uff0cOAT1\uff0cOAT3\uff0cOATP1B1\uff0c\u548cOCT2\uff0c\u4f46\u4e0d\u6291\u5236P-gp\uff0cMRP2\uff0c\u6216OATP1B3\u3002IDHIFA\u7684\u5171\u540c\u7ed9\u836f\u53ef\u80fd\u589e\u52a0\u6216\u51cf\u4f4e\u7ec4\u5408\u7684\u6fc0\u7d20\u907f\u5b55\u836f\u7684\u6d53\u5ea6\u3002\u5728\u6b64\u65f6\u4e0d\u77e5\u9053\u8fd9\u4e2a\u6f5c\u5728\u7684\u836f\u7269\u76f8\u4e92\u4f5c\u7528\u7684\u4e34\u5e8a\u4e0a\u610f\u4e49\u3002
13 \u975e\u4e34\u5e8a\u6bd2\u7406\u5b66
13.1 \u764c\u53d1\u751f\uff0c\u7a81\u53d8\u53d1\u751f\uff0c\u751f\u80b2\u529b\u53d7\u635f
\u672a\u66fd\u7528enasidenib\u8fdb\u884c\u81f4\u764c\u6027\u7814\u7a76\u3002
Enasidenib\u4e0d\u662f\u81f4\u7a81\u53d8\u6027\u5728\u4e00\u4e2a\u5728\u4f53\u5916\u7ec6\u83cc\u56de\u590d\u7a81\u53d8(Ames)\u8bd5\u9a8c\u3002Enasidenib\u4e0d\u662f\u81f3\u7578\u53d8\u6027\u5728\u4e00\u9879\u5728\u4f53\u5916\u4eba\u6dcb\u5df4\u7ec6\u80de\u67d3\u8272\u4f53\u7578\u53d8\u8bd5\u9a8c\uff0c\u6216\u5728\u4e00\u9879\u4f53\u5185\u5927\u9f20\u9aa8\u9ad3\u5fae\u6838\u8bd5\u9a8c\u3002
\u5c1a\u672a\u7528enasidenib\u5728\u52a8\u7269\u4e2d\u8fdb\u884c\u751f\u80b2\u529b\u7814\u7a76\u3002\u5728\u91cd\u590d\u7ed9\u836f\u6bd2\u6027\u7814\u7a76\u7528\u6bcf\u5929\u4e24\u6b21\u53e3\u670d\u7ed9\u4e88enasidenib\u5728\u5927\u9f20\u76f4\u81f390-\u5929\u65f6\u95f4\uff0c\u5728\u96c4\u6027\u548c\u96cc\u6027\u751f\u6b96\u5668\u5b98\u88ab\u62a5\u9053\u7684\u53d8\u5316\u5305\u62ec\u66f2\u7ec6\u7cbe\u7ba1\u817f\u578b\u6027\u53d8\u6027\uff0c\u7cbe\u5b50\u51cf\u4f4e\uff0c\u7cbe\u56ca\u548c\u524d\u5217\u817a\u7684\u840e\u7f29\uff0c\u9ec4\u4f53\u51cf\u5c0f\u548c\u5375\u5de2\u4e2d\u65e0\u529b\u6ee4\u6ce1\u589e\u52a0\uff0c\u548c\u5b50\u5bab\u4e2d\u840e\u7f29\u3002
14 \u4e34\u5e8a\u7814\u7a76
14.1 \u6025\u6027\u9ad3\u6027\u767d\u8840\u75c5
\u5728\u4e00\u9879\u5f00\u653e\uff0c\u5355\u81c2\uff0c\u591a\u4e2d\u5fc3\uff0c\u4e24-\u961f\u5217\u4e34\u5e8a\u8bd5\u9a8c(\u7814\u7a76AG221-C-001\uff0cNCT01915498)\u7684199\u4f8b\u6210\u5e74\u60a3\u8005\u6709\u590d\u53d1\u6216\u96be\u6cbb\u6027AML\u548c\u4e00\u4e2aIDH2\u7a81\u53d8\uff0c\u60a3\u8005\u88ab\u8d4b\u4e88\u63a5\u53d7100 mg\u6bcf\u5929\u7ed9\u836f\u88ab\u8bc4\u4ef7Idhifa\u7684\u7597\u6548\u3002\u961f\u52171\u5305\u62ec101\u60a3\u8005\u548c\u961f\u52172\u5305\u62ec98\u60a3\u8005\u3002 IDH2\u7a81\u53d8\u88ab\u5f53\u5730\u4e00\u4e2a\u8bca\u65ad\u6d4b\u8bd5\u548c\u88abAbbott RealTime\u2122 IDH2\u5206\u6790\u56de\u987e\u5730\u786e\u8bc1\uff0c\u6216\u88abAbbott RealTime\u2122 IDH2\u5206\u6790\u9884\u671f\u5730\u9274\u5b9a\uff0c\u5b83\u662fFDA-\u6279\u51c6\u7684\u6d4b\u8bd5\u4e3a\u9009\u62e9\u6709AML\u60a3\u8005\u4e3a\u7528IDHIFA\u6cbb\u7597\u3002IDHIFA\u662f\u88ab\u53e3\u670d\u5730\u7ed9\u4e88\u5728\u5f00\u59cb\u7ed9\u836f\u4e88100 mg\u6bcf\u5929\u76f4\u81f3\u75be\u75c5\u8fdb\u5c55\u6216\u4e0d\u53ef\u63a5\u53d7\u6bd2\u6027\u3002\u5141\u8bb8\u51cf\u4f4e\u5242\u91cf\u5904\u7406\u4e0d\u826f\u4e8b\u4ef6\u3002
\u5728\u88684\u4e2d\u663e\u793a\u57fa\u7ebf\u4eba\u53e3\u7edf\u8ba1\u548c\u75be\u75c5\u7279\u5f81\u3002\u5728\u4e24\u4e2a\u7814\u7a76\u961f\u5217\u57fa\u7ebf\u4eba\u53e3\u7edf\u8ba1\u548c\u75be\u75c5\u7279\u5f81\u4e3a\u76f8\u4f3c\u3002<\/p>\n\n\n\n

\u5728\u5b8c\u5168\u7f13\u89e3(CR)\/\u5b8c\u5168\u7f13\u89e3\u7387\u6709\u90e8\u5206\u8840\u6db2\u5b66\u6062\u590d(CRh)\uff0cCR\/CRh\u7684\u65f6\u95f4\uff0c\u548c\u4ece\u8f93\u6ce8\u4f9d\u8d56\u6027\u81f3\u8f93\u6ce8\u72ec\u7acb\u65e0\u5173\u7684\u8f6c\u6362\u7387\u7684\u57fa\u7840\u4e0a\u786e\u5b9a\u7597\u6548\u3002\u88685\u663e\u793a\u7597\u6548\u7ed3\u679c\u548c\u4e24\u961f\u5217\u662f\u76f8\u4f3c\u3002\u4e2d\u4f4d\u968f\u8bbf\u4e3a6.6\u6708(\u8303\u56f4\uff0c0.4\u81f327.7\u6708)\u3002\u89c2\u5bdf\u5230\u6709\u6216R140\u6216R172\u7a81\u53d8\u60a3\u8005\u4e2d\u76f8\u4f3c\u7684CR\/CRh\u7387\u3002<\/p>\n\n\n\n

\u5bf9\u5b9e\u73b0\u4e00\u4e2aCR\/CRh\u60a3\u8005\uff0c\u81f3\u9996\u6b21\u53cd\u5e94\u4e2d\u4f4d\u65f6\u95f4\u4e3a1.9\u6708(\u8303\u56f4\uff0c0.5\u81f37.5\u6708)\u548c\u81f3CR\/CRh\u6700\u4f73\u53cd\u5e94\u4e2d\u4f4d\u65f6\u95f4\u4e3a3.7\u6708(\u8303\u56f4\uff0c0.6\u81f311.2\u6708)\u300246\u4f8b\u60a3\u8005\u5b9e\u73b0CR\/CRh\u7684\u6700\u4f73\u53cd\u5e94\u4e2d\uff0c39(85%) \u5728\u5f00\u59cbIDHIFA\u76846\u6708\u5185\u5b9e\u73b0\u3002.
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.<\/p>\n\n\n\n

.<\/p>\n\n\n\n

.<\/p>\n\n\n\n

.<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

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