{"id":111961,"date":"2019-05-17T00:00:50","date_gmt":"2019-05-20T01:28:11","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/111961\/"},"modified":"2019-05-20T09:28:16","modified_gmt":"2019-05-20T01:28:16","slug":"747f4712d5","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/111961\/","title":{"rendered":"\u4ee3\u8c22\u4ea7\u7269\u5b89\u5168\u6027\u8bc4\u4ef7(MIST)\u7684\u201c\u5341\u5e74\u4e4b\u75d2\u201d"},"content":{"rendered":"
\n
<\/section>\n

\"\u4ee3\u8c22\u4ea7\u7269\u5b89\u5168\u6027\u8bc4\u4ef7(MIST)\u7684\u201c\u5341\u5e74\u4e4b\u75d2\u201d\"<\/p>\n


<\/p>\n

\n
\n
\n
\n
\"\u4ee3\u8c22\u4ea7\u7269\u5b89\u5168\u6027\u8bc4\u4ef7(MIST)\u7684\u201c\u5341\u5e74\u4e4b\u75d2\u201d\"<\/section>\n<\/section>\n
\n
\n

\u4f17\u6240\u5468\u77e5\uff0c\u836f\u7269\u8fdb\u5165\u673a\u4f53\u540e\uff0c\u80fd\u591f\u5728\u5404\u79cd\u9176\u7684\u50ac\u5316\u4e0b\u53d1\u751f\u4ee3\u8c22\u8f6c\u53d8\uff0c\u751f\u6210\u7ed3\u6784\u76f8\u8fd1\u7684\u4ee3\u8c22\u4ea7\u7269\u3002\u867d\u7136\u7ed3\u6784\u4e0e\u6bcd\u836f\u7c7b\u4f3c\uff0c\u4f46\u662f\u4ee3\u8c22\u4ea7\u7269\u7edd\u5bf9\u7b97\u662f\u9879\u76ee\u7814\u53d1\u4e2d\u51fa\u73b0\u7684\u65b0\u5316\u5b66\u6210\u5206\u3002\u5229\u7528\u52a8\u7269\u548c\u4f53\u5916\u624b\u6bb5\u5bf9\u5019\u9009\u5316\u5408\u7269\u8fdb\u884c\u6bd2\u7406\u7814\u7a76\uff0c\u901a\u5e38\u66f4\u5173\u6ce8\u6bcd\u836f\u7279\u6027\uff0c\u800c\u975e\u4ee3\u8c22\u4ea7\u7269\u3002\u5e76\u4e14\u52a8\u7269\u79cd\u5c5e\u4e0e\u4eba\u4f53\u53ef\u80fd\u5b58\u5728\u5dee\u5f02\uff0c\u4e0d\u80fd\u7b80\u5355\u5047\u8bbe\u6240\u4ea7\u751f\u7684\u4ee3\u8c22\u4ea7\u7269\u5c31\u4e0e\u4eba\u4f53\u5c31\u76f8\u540c\uff0c\u5f53\u67d0\u79cd\u4ee3\u8c22\u4ea7\u7269\u5728\u4eba\u4f53\u4e2d\u7684\u66b4\u9732\u91cf\u4e0e\u52a8\u7269\u79cd\u5c5e\u4e0d\u6210\u6bd4\u4f8b(disproportional)\u65f6\uff0c\u5c31\u5b58\u5728\u5b89\u5168\u6027\u98ce\u9669\u3002\u9274\u4e8e\u6b64\uff0c\u4ee3\u8c22\u4ea7\u7269\u5b89\u5168\u6027\u8bc4\u4ef7(MIST\uff0cMetabolites in Safety Testing)\u7684\u6982\u5ff5\u88ab\u63d0\u51fa\u3002<\/span><\/p>\n<\/section>\n<\/section>\n

\"\u4ee3\u8c22\u4ea7\u7269\u5b89\u5168\u6027\u8bc4\u4ef7(MIST)\u7684\u201c\u5341\u5e74\u4e4b\u75d2\u201d\"<\/section>\n<\/section>\n<\/section>\n
\n


<\/p>\n<\/section>\n<\/section>\n

\u81ea\u4e0a\u4e16\u7eaa90\u5e74\u4ee3\u521d\uff0c\u6db2\u8d28\u8054\u7528\u6280\u672f(LC-MS)\u53d6\u5f97\u4e86\u7a81\u7834\u6027\u53d1\u5c55\uff0c\u9769\u65b0\u4e86\u836f\u7269\u4ee3\u8c22\u9886\u57df\u7684\u6280\u672f\u624b\u6bb5\uff0c\u5728\u8bf8\u5982\u8840\u6d46\u7b49\u590d\u6742\u57fa\u8d28\u4e2d\u4ee3\u8c22\u4ea7\u7269\u7684\u9274\u5b9a\u4e5f\u53d8\u5f97\u76f8\u5bf9\u5bb9\u6613\u3002\u518d\u52a0\u4e0a\u653e\u5c04\u6027\u6807\u8bb0\u7684ADME(\u5438\u6536\u3001\u5206\u5e03\u3001\u4ee3\u8c22\u548c\u6392\u6cc4)\u7814\u7a76\u80fd\u591f\u5bf9\u8840\u6d46\u3001\u5c3f\u6db2\u548c\u7caa\u4fbf\u751f\u6210\u5b9a\u91cf\u4ee3\u8c22\u4ea7\u7269\u8c31\u56fe\uff0c\u4f7f\u5f97\u4ee3\u8c22\u4ea7\u7269\u7814\u7a76\u6210\u4e3a\u836f\u7269\u7814\u53d1\u7684\u91cd\u8981\u7ec4\u6210\u90e8\u5206\u3002<\/span><\/p>\n

 <\/span><\/p>\n

\u867d\u7136\u4e00\u822c\u836f\u7269\u5bf9\u5f00\u53d1\u56e2\u961f\u6765\u8bf4\u90fd\u5f88\u6e05\u695a\u4ee3\u8c22\u4ea7\u7269\u53ef\u80fd\u6709\u836f\u6548\u6d3b\u6027\u6216\u8005\u6bd2\u6027\u4f5c\u7528\uff0c\u9700\u8981\u4e88\u4ee5\u8003\u5bdf\uff0c\u4f46\u662f\u5177\u4f53\u5230\u9879\u76ee\uff0c\u5374\u9762\u4e34\u4ee5\u4e0b\u95ee\u9898\uff1a<\/span><\/p>\n


<\/span><\/p>\n

1.\u54ea\u4e9b\u4ee3\u8c22\u4ea7\u7269\u9700\u8981\u7eb3\u5165\u5b89\u5168\u8bc4\u4ef7\u8303\u56f4\uff1f<\/span><\/strong><\/p>\n


<\/span><\/strong><\/p>\n

2.\u662f\u5426\u5b58\u5728\u4ee3\u8c22\u7269\u66b4\u9732\u91cf\u7684\u9608\u503c\uff0c\u6765\u51b3\u5b9a\u8fdb\u4e00\u6b65\u7814\u7a76\u7684\u5fc5\u8981\u6027\uff1f<\/span><\/strong><\/p>\n


<\/span><\/strong><\/p>\n

3.\u4ee3\u8c22\u4ea7\u7269\u7684\u5316\u5b66\u7ed3\u6784\u662f\u5426\u6709\u5fc5\u8981\u83b7\u5f97\uff1f<\/span><\/strong><\/p>\n


<\/span><\/p>\n

\u8fd9\u4e9b\u90fd\u9700\u8981\u6709\u76f8\u5173\u53ef\u9075\u5faa\u7684\u6cd5\u89c4\u6216\u6307\u5bfc\u539f\u5219\u3002<\/span><\/p>\n

\n
\n


<\/p>\n

\n
\n
\n
\n
MIST\u6307\u5bfc\u539f\u5219\u7684\u53d8\u8fc1<\/span><\/section>\n
\n
<\/section>\n
<\/section>\n
\n
\n
<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n
\n


<\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

2002\u5e74\uff0c\u9971\u53d7\u4eba\u4f53\u4ee3\u8c22\u4ea7\u7269\u5b89\u5168\u6027\u56f0\u6270\u7684\u5de5\u4e1a\u754c\u7387\u5148\u201c\u53d1\u96be\u201d\uff0c\u4e00\u7fa4\u6765\u81ea\u4e0d\u540c\u516c\u53f8\u548c\u7ec4\u7ec7\u7684\u79d1\u5b66\u5bb6\u5171\u540c\u53d1\u8868\u4e86\u836f\u7269\u4ee3\u8c22\u4ea7\u7269\u98ce\u9669\u8bc4\u4f30\u7684\u5efa\u8bae\u4e66(\u53c2\u8003\u6587\u7ae02)\uff0c\u6587\u7ae0\u63d0\u51fa\u5728\u4eba\u4f53\u8840\u6d46\u4e2d\u66b4\u9732\u91cf\u5360\u6bd4\u8d85\u8fc7\u836f\u7269\u76f8\u5173\u7269\u8d28\u603b\u91cf25%\u7684\u4ee3\u8c22\u4ea7\u7269\uff0c\u5fc5\u987b\u5728\u4e34\u5e8a\u524d\u6bd2\u7406\u79cd\u5c5e\u7814\u7a76\u4e2d\u5f97\u5230\u8986\u76d6\uff0c\u8fd9\u662f\u9996\u6b21\u5173\u4e8eMIST\u7684\u9610\u8ff0\u3002<\/span><\/p>\n


<\/span><\/p>\n

2008\u5e74\uff0cFDA\u7ec8\u4e8e\u53d1\u5e03\u4e86MIST\u7684\u6307\u5bfc\u539f\u5219\uff0c\u5c06\u4ee3\u8c22\u7269\u7684\u9608\u503c\u8c03\u6574\u4e3a\u4eba\u4f53\u8840\u6d46\u4e2d\u836f\u7269\u539f\u578b\u768410%\u3002<\/span><\/p>\n


<\/span><\/p>\n

2010\u5e74\u5728\u7efc\u5408\u4e86\u66f4\u5e7f\u6cdb\u7684\u610f\u89c1\u540e\uff0cICH\u53d1\u5e03\u4e86\u6307\u5bfc\u610f\u89c1\uff0c\u63d0\u51fa\u5728\u4eba\u4f53\u8840\u6d46\u4e2d\u66b4\u9732\u91cf\u5360\u6bd4\u8d85\u8fc7\u836f\u7269\u76f8\u5173\u7269\u8d28\u603b\u91cf10%\u7684\u4ee3\u8c22\u4ea7\u7269\uff0c\u5728\u5f00\u5c55\u5927\u89c4\u6a21\u4e34\u5e8a\u8bd5\u9a8c\u524d\uff0c\u6709\u5fc5\u8981\u5bf9\u5176\u8fdb\u884c\u975e\u4e34\u5e8a\u5b89\u5168\u6027\u7814\u7a76<\/strong>(ICH M3(R2)\u3002FDA\u968f\u540e\u8ddf\u8fdb\uff0c\u57282016\u5e74\u4fee\u6539\u6307\u5bfc\u539f\u5219\u4e0eICH\u770b\u9f50\u3002<\/span><\/p>\n


<\/p>\n

\"\u4ee3\u8c22\u4ea7\u7269\u5b89\u5168\u6027\u8bc4\u4ef7(MIST)\u7684\u201c\u5341\u5e74\u4e4b\u75d2\u201d\"<\/p>\n

\u56fe\u7247\u6574\u7406\u81ea\u53c2\u8003\u6587\u7ae0<\/span><\/p>\n

 <\/span><\/p>\n

\u8fd9\u4e9b\u6307\u5bfc\u539f\u5219\u5728\u836f\u7269\u5b89\u5168\u6027\u7814\u7a76\u65b9\u9762\u7684\u4fc3\u8fdb\u4f5c\u7528\u6bcb\u5eb8\u7f6e\u7591\uff0c\u4f46\u66f4\u91cd\u8981\u7684\u662f\u5b83\u4eec\u63d0\u4f9b\u4e86\u4e00\u4e2a\u6846\u67b6\uff0c\u8ba9\u836f\u7269\u7814\u53d1\u5bf9\u4ee3\u8c22\u4ea7\u7269\u7684\u7814\u7a76\u6709\u636e\u53ef\u4f9d\u3002\u4ece\u4e34\u5e8a\u524d\u5230\u4e34\u5e8a\uff0c\u6bcf\u4e2a\u9636\u6bb5\u6240\u8981\u89e3\u51b3\u7684\u836f\u7269\u4ee3\u8c22\u95ee\u9898\u4e0d\u5c3d\u76f8\u540c\uff0c\u53ef\u80fd\u56e0\u7b56\u7565\u53ca\u9776\u70b9\u800c\u4e0d\u540c\u3002\u5982\u80bf\u7624\u665a\u671f\u3001\u8010\u836fHIV(\u827e\u6ecb\u75c5\u75c5\u6bd2)\u3001\u5148\u5929\u6027\u9176\u7f3a\u4e4f\u75c7\u7b49\u4e25\u91cd\u75be\u75c5\u7684\u836f\u7269\u5f00\u53d1\uff0c\u5bf9\u4ee3\u8c22\u4ea7\u7269\u5b89\u5168\u6027\u7814\u7a76\u6709\u76f8\u5e94\u7b80\u5316\u63aa\u65bd\u3002\u5bf9\u5e38\u89c4\u9879\u76ee\uff0c\u4ee3\u8c22\u4ea7\u7269\u5178\u578b\u7b56\u7565\u53ef\u4ee5\u5206\u4e3a\u4e09\u4e2a\u9636\u6bb5\u6765\u63cf\u8ff0\uff1a<\/span><\/p>\n

 <\/span><\/p>\n

\u7b2c\u4e00\u9636\u6bb5 (Pre-IND)<\/span><\/strong><\/p>\n


<\/span><\/strong><\/p>\n

\u5728\u6b64\u9636\u6bb5\uff0c\u836f\u7269\u4ee3\u8c22\u7814\u7a76\u4e3b\u8981\u9488\u5bf9\u4f53\u5916(in vitro)\u548c\u5b9e\u9a8c\u52a8\u7269(in vivo)\uff0c\u5982\u809d\u5fae\u7c92\u4f53\u3001\u809d\u7ec6\u80de\u3001\u809dS9\uff0c\u91cd\u7ec4\u9176\u6216\u8005\u8840\u6d46\u7b49\u3002\u5229\u7528\u8fd9\u4e9b\u4f53\u5916\u6a21\u578b\u6765\u5b75\u80b2\u4ee3\u8c22\u4ea7\u7269\uff0c\u7ed3\u5408\u4fdd\u7559\u65f6\u95f4\u548c\u8d28\u8c31\u88c2\u89e3\u89c4\u5f8b\u6765\u6bd4\u8f83\u4e0d\u540c\u79cd\u5c5e\u548c\u4eba\u7c7b\u7684\u4ee3\u8c22\u4ea7\u7269\u5b9a\u6027\/\u5b9a\u91cf\u7684\u5dee\u5f02\uff0c\u636e\u6b64\u9009\u62e9\u5408\u9002\u7684\u79cd\u5c5e\u5f00\u5c55\u6bd2\u7406\u7814\u7a76\u3002\u6216\u662f\u7814\u7a76\u52a8\u7269\u7ed9\u836f\u540e\u7684\u4f53\u5185\u4ee3\u8c22\u4ea7\u7269\uff0c\u548c\u4f53\u5916\u7814\u7a76\u76f8\u8f85\u76f8\u6210\u3002\u52a8\u7269\u7684\u4f53\u5185\u7ed3\u679c\u5e76\u4e0d\u80fd\u76f4\u63a5\u8f6c\u5316\u4e3a\u5bf9\u4e34\u5e8a\u7684\u51c6\u786e\u9884\u6d4b\uff0c\u800c\u662f\u901a\u8fc7\u5206\u6790\u52a8\u7269\u7684\u4e3b\u8981\u4ee3\u8c22\u4ea7\u7269\uff0c\u5224\u65ad\u4ee3\u8c22\u7269\u8c31\u662f\u5426\u80fd\u591f\u8986\u76d6\u4eba\u4f53\u7ed3\u679c\uff0c\u8fd9\u5bf9\u4e34\u5e8a\u7684\u5b89\u5168\u6027\u7814\u7a76\u81f3\u5173\u91cd\u8981\u3002<\/span><\/p>\n

 <\/span><\/p>\n

\u7b2c\u4e8c\u9636\u6bb5 (\u4e34\u5e8aI\u671f)<\/span><\/strong><\/p>\n


<\/span><\/strong><\/p>\n

\u4e34\u5e8aI\u671f\u591a\u5242\u91cf\u9012\u589e\u8bd5\u9a8c(MAD)\u7684\u7a33\u6001\u8840\u6d46\u6837\u672c\u53ef\u4ee5\u7528\u4e8e\u4eba\u4f53\u4ee3\u8c22\u4ea7\u7269\u7814\u7a76\uff0c\u8fd9\u901a\u5e38\u4e5f\u662f\u9996\u6b21\u5f97\u5230\u836f\u7269\u7684\u4eba\u4f53\u4ee3\u8c22\u4ea7\u7269\u6570\u636e\u3002LC-MS\u7075\u654f\u5ea6\u867d\u7136\u53ef\u4ee5\u6ee1\u8db3\u5fae\u91cf\u4ee3\u8c22\u4ea7\u7269\u7684\u5206\u6790\uff0c\u4f46\u662f\u5408\u6210\u4ee3\u8c22\u4ea7\u7269\u6807\u51c6\u54c1\u5de5\u4f5c\u91cf\u8fc7\u5927\uff0c\u53ef\u4ee5\u6839\u636e\u7d2b\u5916\u5438\u6536\u6570\u636e\u8ba1\u7b97\u4ee3\u8c22\u4ea7\u7269\u4e0e\u6bcd\u836f\u7684\u76f8\u5bf9\u4e30\u5ea6\u3002<\/span><\/p>\n

 <\/span><\/p>\n

\u5bf9\u4e8e\u6307\u5bfc\u539f\u5219\u4e2d\u4ee3\u8c22\u4ea7\u7269\u8d85\u8fc7\u836f\u7269\u76f8\u5173\u7269\u8d28\u603b\u91cf\u768410%\uff0c\u5982\u4f55\u5224\u65ad\uff1f\u5982\u679c\u5c06\u6bcd\u836f\u548c\u6240\u6709\u4ee3\u8c22\u4ea7\u7269\u8fdb\u884c\u5b9a\u91cf\u52a0\u548c\uff0c\u9700\u8981\u5927\u91cf\u5408\u6210\u6807\u51c6\u54c1\uff0c\u663e\u7136\u4e0d\u73b0\u5b9e\u3002\u603b\u4f53\u6765\u8bb2\u5728\u8fd9\u4e2a\u9636\u6bb5\uff0c\u8fd8\u4e0d\u9700\u8981\u51c6\u786e\u5b9a\u91cf\uff0c\u53ea\u8981\u5bf9\u6bd4NOAEL(\u65e0\u660e\u663e\u635f\u5bb3\u4f5c\u7528\u5242\u91cf)\u4e0b\u6bd2\u7406\u79cd\u5c5e\u7684\u4ee3\u8c22\u4ea7\u7269\u548c\u4e34\u5e8a\u836f\u6548\u5242\u91cf\u4e0b\u8840\u6d46\u4ee3\u8c22\u4ea7\u7269\u7684\u7ed3\u679c\uff0c\u5224\u65ad\u662f\u5426\u5b58\u5728\u4e34\u5e8a\u524d\u672a\u8986\u76d6\u7684\u4ee3\u8c22\u4ea7\u7269\u5373\u53ef\u3002\u5e38\u7528\u65b9\u6cd5\u6709\u4e24\u79cd\uff0c\u4e00\u79cd\u662f\u7528Hamilton Pooling\u6cd5\u8ba1\u7b97\u4ee3\u8c22\u4ea7\u7269\u7684\u201c\u66b4\u9732\u91cf\u500d\u6570\u201d\uff1b\u53e6\u4e00\u79cd\u662f\u4f9d\u9760\u540c\u4f4d\u7d20\u6807\u8bb0\u8bd5\u9a8c\uff0c\u6839\u636e\u556e\u9f7f\u7c7b\u540c\u4f4d\u7d20\u6807\u8bb0\u7684\u7269\u8d28\u5e73\u8861\u7ed3\u679c\uff0c\u5bf9\u6bd4\u5927\u9f20\u7684\u540c\u4f4d\u7d20\u6807\u8bb0\u4ee3\u8c22\u4ea7\u7269\u6d53\u5ea6\u5f97\u5230\u56e0\u5b50\uff0c\u8fdb\u800c\u6362\u7b97\u4eba\u4f53\u4ee3\u8c22\u4ea7\u7269\u7684\u6d53\u5ea6\u3002<\/span><\/p>\n

 <\/span><\/p>\n

\u786e\u5b9a\u4e86\u4e34\u5e8a\u524d\u4ee3\u8c22\u4ea7\u7269\u7684\u8986\u76d6\u60c5\u51b5\uff0c\u5c31\u53ef\u4ee5\u51b3\u5b9a\u662f\u5426\u9700\u8981\u5408\u6210\u4ee3\u8c22\u7269\uff0c\u662f\u5426\u9700\u8981\u5f00\u5c55\u4e13\u95e8\u7684\u4f53\u5185\u548c\u6bd2\u7406\u7814\u7a76\u3002\u4f46\u662f\u5f88\u591a\u7814\u7a76\u56e2\u961f\u9009\u62e9\u628a\u8fd9\u90e8\u5206\u5de5\u4f5c\u5f80\u540e\u653e\u4e00\u653e\uff0c\u5728\u5b8c\u6210\u4eba\u4f53\u540c\u4f4d\u7d20ADME\u7814\u7a76\u540e\u518d\u505a\u51b3\u5b9a\uff0c\u66f4\u6709\u5c06\u9488\u5bf9\u4ee3\u8c22\u4ea7\u7269\u7684\u7814\u7a76\u653e\u5728\u4e34\u5e8a\u6982\u5ff5\u9a8c\u8bc1(PoC)\u4e4b\u540e\u7684\uff0c\u8fd9\u4e5f\u7b97\u662f\u907f\u514d\u7531\u4e8ePoC\u5931\u8d25\u505a\u592a\u591a\u201c\u65e0\u7528\u529f\u201d\u3002<\/span><\/p>\n


<\/p>\n

\"\u4ee3\u8c22\u4ea7\u7269\u5b89\u5168\u6027\u8bc4\u4ef7(MIST)\u7684\u201c\u5341\u5e74\u4e4b\u75d2\u201d\"<\/p>\n

\u56fe\u7247\u6e90\u81eaFDA\u7f51\u7ad9<\/span><\/p>\n

 <\/span><\/p>\n

\u7b2c\u4e09\u9636\u6bb5 (\u4e34\u5e8aII\u671f\u540e\uff0c\u4e34\u5e8aIII\u671f\u524d)<\/span><\/strong> <\/span><\/p>\n


<\/span><\/p>\n

\u56e0\u4e3a\u5bf9\u4e3b\u8981\u4ee3\u8c22\u4ea7\u7269\u7684\u7814\u7a76\u5fc5\u987b\u5728\u6269\u5927\u4e34\u5e8a\u524d\u5b8c\u6210\uff0c\u6240\u4ee5\u5728\u8fd9\u4e2a\u9636\u6bb5\u6240\u6709\u5fc5\u8981\u7684\u4ee3\u8c22\u7269\u7814\u7a76\u90fd\u5e94\u8be5\u7ed3\u675f\u4e86\u3002\u5305\u62ec\u4ee3\u8c22\u7269\u5b9a\u91cf\u3001\u5229\u7528\u9ad8\u5206\u8fa8\u8d28\u8c31\u786e\u5b9a\u672a\u77e5\u4ee3\u8c22\u4ea7\u7269\u3001\u4eba\u4f53\u540c\u4f4d\u7d20\u6807\u8bb0ADME\u7814\u7a76(\u8fd8\u53ef\u4ee5\u7528\u4e8e\u786e\u5b9a\u54ea\u4e9b\u4ee3\u8c22\u7269\u9700\u8981DDI\u8bc4\u4f30)\u4ee5\u83b7\u5f97\u6240\u6709\u4ee3\u8c22\u7269\u8c31\u56fe\u7b49\u3002<\/span><\/p>\n

 <\/span><\/p>\n

\n
\n
\n
\n
\u5bf9MIST\u7684\u4e00\u4e9b\u601d\u8003<\/span><\/section>\n
\n
<\/section>\n
<\/section>\n
\n
\n
<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n
\n


<\/p>\n<\/section>\n<\/section>\n

<\/span><\/p>\n

\u4ece2008\u5e74FDA\u53d1\u5e03MIST\u6307\u5bfc\u539f\u5219\u81f3\u4eca\u5df2\u7ecf\u5341\u4f59\u5e74\u4e86\uff0c\u8fd9\u5341\u5e74\u95f4\uff0c\u5bf9\u4ee3\u8c22\u4ea7\u7269\u548c\u4ee3\u8c22\u5b89\u5168\u6027\u7684\u91cd\u89c6\u9010\u6e10\u6df1\u5165\u4eba\u5fc3\uff0c\u5236\u836f\u5de5\u4e1a\u5df2\u7ecf\u9002\u5e94\u4e86MIST\u6307\u5357\u7684\u8981\u6c42\uff0c\u5927\u91cf\u6848\u4f8b\u4e5f\u4e3a\u7814\u53d1\u56e2\u961f\u7684\u4ee3\u8c22\u7269\u7814\u7a76\u8ba1\u5212\u63d0\u4f9b\u4e86\u5f88\u597d\u7684\u501f\u9274\u3002\u4f46\u662f\u4e5f\u9047\u5230\u4e86\u4e0d\u5c11\u7684\u95ee\u9898\uff0c\u9996\u5148\uff0c\u5f88\u5c11\u6709\u9879\u76ee\u771f\u7684\u5f00\u5c55\u8fc7\u5bf9\u4ee3\u8c22\u7269\u7684\u6bd2\u7406\u7814\u7a76\uff0c\u4e5f\u5f88\u96be\u627e\u5230\u5faa\u73af\u4ee3\u8c22\u7269\u76f4\u63a5\u5f15\u8d77\u5b89\u5168\u95ee\u9898\u7684\u6848\u4f8b<\/strong>\u3002\u5f88\u591a\u60c5\u51b5\u4e0b\uff0c\u660e\u660e\u5b89\u5168\u95ee\u9898\u5df2\u7ecf\u6307\u5411\u4ee3\u8c22\u7269\uff0c\u4f46\u6700\u7ec8\u53c8\u62ff\u4e0d\u51fa\u5341\u8db3\u7684\u8bc1\u636e\u3002\u4e00\u65b9\u9762\u8fd9\u53ef\u80fd\u662f\u7531\u4e8e\u4ee3\u8c22\u7269\u548c\u6bcd\u836f\u7684\u6027\u8d28\u5f88\u96be\u533a\u5206\uff0c\u53e6\u4e00\u65b9\u9762\uff0c\u5bf9\u4e8e\u4e00\u4e9b\u6d3b\u6027\u4e2d\u95f4\u4ee3\u8c22\u7269\uff0c\u5e38\u89c4\u5206\u6790\u65b9\u6cd5\u6709\u65f6\u68c0\u6d4b\u4e0d\u5230\uff0c\u9020\u6210\u5f88\u5927\u96be\u5ea6\u3002\u836f\u7269\u4f9d\u5e15\u5217\u51c0 (Empagliflozin) \u7ed9\u4e88\u5927\u9f20\u540e\uff0c\u89c2\u5bdf\u5230\u660e\u663e\u7684\u7531\u4ee3\u8c22\u7269\u4ecb\u5bfc\u7684\u6bd2\u6027\uff0c\u4f46\u672a\u53d1\u73b0\u6d3b\u6027\u4ee3\u8c22\u7269\u548c\u4e0b\u6e38\u4ee3\u8c22\u7269\u3002<\/span><\/p>\n


<\/p>\n

\"\u4ee3\u8c22\u4ea7\u7269\u5b89\u5168\u6027\u8bc4\u4ef7(MIST)\u7684\u201c\u5341\u5e74\u4e4b\u75d2\u201d\"<\/p>\n

\u6848\u4f8b\u4e00(\u56fe\u7247\u6574\u7406\u81ea\u53c2\u8003\u6587\u7ae0)<\/span><\/p>\n

 <\/span><\/p>\n

\u5176\u6b21\uff0c\u53cd\u5e94\u6027\u4ee3\u8c22\u7269\u6216\u4e0b\u6e38\u4ea7\u7269(\u5982\u8c37\u80f1\u7518\u80bd\u6216\u534a\u80f1\u6c28\u9178\u7ed3\u5408\u7269\u7684\u4ee3\u8c22\u7269)\u7531\u4e8e\u5176\u5206\u5b50\u91cf\u548c\u4eb2\u6c34\u6027\u9ad8\uff0c\u901a\u5e38\u901a\u8fc7\u80c6\u6c41\u548c\/\u6216\u5c3f\u6db2\u8fc5\u901f\u6392\u6cc4\uff0c\u56e0\u6b64\u5f88\u96be\u6839\u636eMIST\u7684\u8981\u6c42\u6bd4\u8f83\u4e0d\u540c\u79cd\u5c5e\u95f4\u53cd\u5e94\u6027\u4ee3\u8c22\u7269\u7684\u66b4\u9732\u91cf\u5dee\u5f02\u3002<\/strong>\u53e6\u5916\uff0c\u5728\u4e00\u4e9b\u7279\u5b9a\u9879\u76ee\u4e2d\u6d4b\u5b9a\u9776\u7ec4\u7ec7\u4e2d\u4ee3\u8c22\u7269\u53ef\u80fd\u66f4\u4e3a\u91cd\u8981\uff0c\u5374\u96be\u4ee5\u5728\u4eba\u4f53\u5f00\u5c55\u3002\u6362\u53e5\u8bdd\u8bf4\uff0c\u968f\u7740\u6280\u672f\u7684\u53d1\u5c55\uff0c\u5bf9\u4ee3\u8c22\u4ea7\u7269\u7684\u7814\u7a76\u8981\u505a\u5230\u4f55\u79cd\u7a0b\u5ea6\uff1fMIST\u6240\u505a\u7684\u4e00\u5207\u662f\u5426\u771f\u7684\u5f71\u54cd\u4e86\u836f\u7269\u5b89\u5168\u6027\u8bc4\u4ef7\uff0c\u8fd9\u4e9b\u90fd\u662f\u672a\u6765\u6211\u4eec\u9700\u8981\u53bb\u601d\u8003\u548c\u89e3\u51b3\u7684\u3002<\/span><\/p>\n


<\/p>\n

\"\u4ee3\u8c22\u4ea7\u7269\u5b89\u5168\u6027\u8bc4\u4ef7(MIST)\u7684\u201c\u5341\u5e74\u4e4b\u75d2\u201d\"<\/p>\n

\u6848\u4f8b\u4e8c(\u56fe\u7247\u6574\u7406\u81ea\u53c2\u8003\u6587\u7ae0)<\/span><\/p>\n

 <\/span><\/p>\n

\u6307\u5bfc\u539f\u5219\u53ea\u662f\u63d0\u4f9b\u4e86\u4e00\u4e2a\u65b9\u5411\uff0c\u5bf9\u6bcf\u4e2a\u9879\u76ee\u4e00\u5b9a\u8981case by case\u7684\u53bb\u9488\u5bf9\u6027\u8bbe\u8ba1\u7814\u7a76\u65b9\u6848\uff0c\u9664\u4e86\u5e38\u89c4\u6bd2\u6027\uff0c\u8fd8\u5e94\u5173\u6ce8\u4ee3\u8c22\u7269\u6f5c\u5728\u7684DDI\u53d1\u751f\u3002\u5409\u975e\u7f57\u9f50 (Gemfibrozil)\u7684\u8461\u8404\u7cd6\u919b\u9178\u5316\u4ee3\u8c22\u7269\u5bf9\u897f\u7acb\u4f10\u4ed6\u6c40(cerivastatin)\u7684\u4ee3\u8c22\u6e05\u9664\u6291\u5236(\u4e3b\u8981\u7531CYP2C8\u548cOATP1B1\u4ecb\u5bfc)\u5bfc\u81f4\u4e86\u4e25\u91cd\u7684\u540e\u679c\u3002\u6b64\u5916\u8fd8\u6709\u4e01\u82ef\u4e19\u916e\u7684\u4ee3\u8c22\u7269\u5bf9CYP2D6\u8868\u8fbe\u6c34\u5e73\u7684\u5f71\u54cd\uff0c\u4ee5\u53ca\u53bb\u7532\u57fa\u5730\u5c14\u786b\u5353\u5bf9CYP3A4\u7684\u6291\u5236\u4f5c\u7528\u7b49\u3002FDA\u548cEMA\u7684\u6307\u5bfc\u539f\u5219\u5206\u522b\u5efa\u8bae\uff0c\u5f53\u4ee3\u8c22\u7269\u7684\u4f53\u5185\u6c34\u5e73\u8fbe\u5230\u6bcd\u836f\u768425%(FDA, 2012)\uff0c\u6216\u66b4\u9732\u91cf\u8d85\u8fc7\u836f\u7269\u603b\u66b4\u9732\u91cf\u768410%\u65f6(EMA, 2012)\uff0c\u9700\u8981\u5bf9\u4ee3\u8c22\u4ea7\u7269\u7684CYP\u6291\u5236\u548c\u8f6c\u8fd0\u4f53\u6291\u5236\u5f00\u5c55\u7814\u7a76<\/strong>\u3002FDA\u57282017\u5e74\u65b0\u7684\u76f8\u5173\u6307\u5bfc\u539f\u5219\u5f81\u6c42\u610f\u89c1\u7a3f\u4e2d\u8fdb\u4e00\u6b65\u8981\u6c42\uff0c\u5bf9\u8b66\u793a\u6027\u5316\u5b66\u7ed3\u6784(\u5b98\u80fd\u56e2)\uff0c\u9700\u8981\u5f00\u5c55TDI(\u65f6\u95f4\u4f9d\u8d56\u6027\u6291\u5236)\u7814\u7a76\uff1b\u5bf9\u6781\u6027\u5c0f\u4e8e\u6bcd\u836f\u4e14\u66b4\u9732\u91cf\u8d85\u8fc7\u6bcd\u836f25%\u7684\u4ee3\u8c22\u4ea7\u7269\uff0c\u4ee5\u53ca\u6781\u6027\u5927\u4e8e\u6bcd\u836f\u4e14\u66b4\u9732\u91cf\u9ad8\u4e8e\u6bcd\u836f\u7684\u4ee3\u8c22\u4ea7\u7269\uff0c\u9700\u8981\u5f00\u5c55\u4ee3\u8c22\u7269\u4f53\u5916DDI\u7814\u7a76\u3002<\/span><\/p>\n

 <\/span><\/p>\n

\u603b\u4e4b\uff0cMIST\u6307\u5bfc\u539f\u5219\u7684\u63d0\u51fa\u4e0d\u4ec5\u4ec5\u662fDMPK\u79d1\u5b66\u5bb6\u7684\u7814\u7a76\u53c2\u8003\uff0c\u5f88\u5927\u7a0b\u5ea6\u4e0a\u4e5f\u8ba9\u836f\u5316\u3001\u836f\u7406\u7b49\u79d1\u5b66\u5bb6\u5bf9\u4ee3\u8c22\u4ea7\u7269\u7684\u5b89\u5168\u6027\u95ee\u9898\u7ed9\u4e88\u8db3\u591f\u7684\u91cd\u89c6\uff0c\u53ea\u6709\u8fd9\u6837\uff0c\u65b0\u836f\u7684\u5b89\u5168\u8bc4\u4ef7\u624d\u4f1a\u66f4\u52a0\u5f7b\u5e95\uff0c\u8fd9\u4e5f\u662fMIST\u5bf9\u836f\u7269\u7814\u53d1\u6700\u5927\u7684\u8d21\u732e\u3002<\/span><\/p>\n

 <\/span><\/p>\n

\u53c2\u8003\u6587\u7ae0\uff1a<\/span><\/p>\n

[1] A Decade in the MIST: Learnings from Investigations of Drug Metabolites in Drug Development under the \u201cMetabolites in Safety Testing\u201d Regulatory Guidance. DOI: https:\/\/doi.org\/10.1124\/dmd.117.079848<\/span><\/p>\n

[2] Drug Metabolites in Safety Testing. DOI:10.1006\/taap.2002.9440<\/span><\/p>\n

[3] Metabolites in safety testing. https:\/\/doi.org\/10.4155\/bio.09.98<\/span><\/p>\n

[4] FDA-Safety Testing of Drug Metabolites Guidance for Industry.<\/span><\/p>\n

[5] Guidance for Industry M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals.<\/span><\/p>\n

[6] Metabolites in Safety Testing: \u201cMIST\u201d for the Clinical Pharmacologist. doi:10.1038\/clpt.2009.283<\/span><\/p>\n


<\/p>\n

\n
\n
\n
\"\u4ee3\u8c22\u4ea7\u7269\u5b89\u5168\u6027\u8bc4\u4ef7(MIST)\u7684\u201c\u5341\u5e74\u4e4b\u75d2\u201d\"<\/section>\n<\/section>\n

\u706b\u70ed\u62a5\u540d\u4e2d\uff01\u535a\u9ccc\u4e9a\u6d32\u8bba\u575b\u5168\u7403\u5065\u5eb7\u8bba\u575b\u5927\u4f1a<\/span><\/a>
<\/p>\n

\u4e3a\u4ec0\u4e48BALB\/c-hCD3E TG\u662f\u66f4\u5408\u9002\u7684CD3\u53cc\u7279\u5f02\u6297\u4f53\u8bc4\u4ef7\u6a21\u578b\uff1f<\/span><\/a>
<\/p>\n

\u591a\u80bd\u7c7b\u836f\u7269\uff1a\u6765\u81ea\u201c\u8001\u6bd2\u7269\u201d\uff0c\u5374\u662f\u201c\u9ec4\u836f\u5e08\u201d<\/span><\/a>
<\/p>\n

\u4ece\u5206\u5b50\u8bbe\u8ba1\u89d2\u5ea6\uff0c\u770b\u84bd\u73af\u7c7b\u836f\u7269\u7ed3\u6784\u53ca\u6bd2\u6027\uff01<\/span><\/a>
<\/p>\n<\/section>\n<\/section>\n


<\/p>\n

\"\u4ee3\u8c22\u4ea7\u7269\u5b89\u5168\u6027\u8bc4\u4ef7(MIST)\u7684\u201c\u5341\u5e74\u4e4b\u75d2\u201d\"<\/span><\/a><\/p>\n

\"\u4ee3\u8c22\u4ea7\u7269\u5b89\u5168\u6027\u8bc4\u4ef7(MIST)\u7684\u201c\u5341\u5e74\u4e4b\u75d2\u201d\"<\/span><\/a><\/p>\n


<\/p>\n

\n
\n
\"\u4ee3\u8c22\u4ea7\u7269\u5b89\u5168\u6027\u8bc4\u4ef7(MIST)\u7684\u201c\u5341\u5e74\u4e4b\u75d2\u201d\"<\/section>\n<\/section>\n
\n

\u7acb\u5373\u89e3\u9501\u4f60\u7684\u638c\u4e0a\u4e13\u4e1a\u5de5\u5177\uff01<\/span><\/p>\n<\/section>\n<\/section><\/div>\n","protected":false},"excerpt":{"rendered":"

\u4f17\u6240\u5468\u77e5\uff0c\u836f\u7269\u8fdb\u5165\u673a\u4f53\u540e\uff0c\u80fd\u591f\u5728\u5404\u79cd\u9176\u7684\u50ac\u5316\u4e0b\u53d1\u751f\u4ee3\u8c22\u8f6c\u53d8\uff0c\u751f\u6210\u7ed3\u6784\u76f8\u8fd1\u7684\u4ee3\u8c22\u4ea7\u7269\u3002\u867d\u7136\u7ed3\u6784\u4e0e\u6bcd\u836f\u7c7b\u4f3c\uff0c\u4f46\u662f\u4ee3 […]<\/p>\n","protected":false},"author":1,"featured_media":111962,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/111961"}],"collection":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/comments?post=111961"}],"version-history":[{"count":1,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/111961\/revisions"}],"predecessor-version":[{"id":111974,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/111961\/revisions\/111974"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media\/111962"}],"wp:attachment":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media?parent=111961"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/categories?post=111961"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/tags?post=111961"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}