{"id":98691,"date":"2019-04-12T00:00:50","date_gmt":"2019-05-17T08:16:15","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/98691\/"},"modified":"2019-05-17T16:16:19","modified_gmt":"2019-05-17T08:16:19","slug":"0d55d3653f","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/98691\/","title":{"rendered":"\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66"},"content":{"rendered":"
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Metabolism and pharmacokinetics of covalent tyrosine kinase inhibitors<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u836f\u5b66\u5b66\u62a5\uff0cActa Pharmaceutica Sinica <\/p>\n

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\"\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66\"<\/section>\n

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\u5218\u6653\u4e91, \u9648\u7b11\u8273, \u949f\u5927\u653e<\/p>\n

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\"\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66\"<\/section>\n

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\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u901a\u8fc7\u4e0e\u9776\u86cb\u767d\u4e2d\u7684\u534a\u80f1\u6c28\u9178\u5f62\u6210\u5171\u4ef7\u952e, \u6291\u5236\u80bf\u7624\u7ec6\u80de\u7684\u4fe1\u53f7\u901a\u8def\u8f6c\u5bfc, \u5177\u6709\u9ad8\u6548\u80fd\u548c\u6301\u7eed\u65f6\u95f4\u957f\u3001\u514b\u670d\u8010\u836f\u6027\u7684\u4f18\u70b9\u3002<\/span><\/p>\n

\u672c\u6587\u7efc\u8ff0\u4e86\u5df2\u7ecf\u4e0a\u5e02\u7684\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66\u3002<\/span><\/p>\n

\u76ee\u524d<\/span>FDA\u6279\u51c6\u4e0a\u5e02\u7684\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u6709\u963f\u6cd5\u66ff\u5c3c\u3001\u6765\u90a3\u66ff\u5c3c\u3001\u8fbe\u514b\u66ff\u5c3c\u3001\u5965\u5e0c\u66ff\u5c3c\u3001\u4f9d\u9c81\u66ff\u5c3c\u548c\u963f\u53ef\u66ff\u5c3c\u3002<\/span><\/p>\n

\u5421\u54af<\/span>\u66ff\u5c3c\u662f\u7531\u4e2d\u56fd\u81ea\u4e3b\u7814\u53d1, \u6700\u8fd1\u83b7\u6279\u4e0a\u5e02\u7684\u6297\u80bf\u7624\u65b0\u836f\u3002\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u80fd\u591f\u4e0e\u8840\u6d46\u86cb\u767d, \u5c24\u5176\u662f\u4eba\u8840\u6e05\u767d\u86cb<\/span>\u767d\u53d1\u751f\u5171\u4ef7\u7ed3\u5408, \u4ece\u800c\u5f71\u54cd\u8fd9\u7c7b\u836f\u7269\u7684\u836f\u52a8\u5b66\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242(tyrosine kinase inhibitors,TKIs) \u53ef\u6291\u5236\u80bf\u7624\u7ec6\u80de\u589e\u6b96, \u5728\u6297\u80bf\u7624\u6cbb\u7597\u4e2d\u53d1\u6325\u7740<\/span>\u91cd\u8981\u4f5c\u7528[1]\u3002<\/span><\/p>\n

\u7b2c1 \u4ee3\u53ef\u9006\u7684\u8868\u76ae\u7ec6\u80de\u751f\u957f\u56e0\u5b50\u53d7\u4f53<\/span>(EGFR) \u6291\u5236\u5242, \u5982\u5409\u975e\u66ff\u5c3c\u548c\u5384\u6d1b\u66ff\u5c3c, \u5bf9\u53d1\u751f<\/span>EGFR\u654f\u611f\u7a81\u53d8(L858R\u548c19 \u53f7\u5916\u663e\u5b50\u5220\u9664) \u7684\u975e\u5c0f\u7ec6<\/span>\u80de\u80ba\u764c(NSCLC) \u60a3\u8005, \u5177\u6709\u663e\u8457\u7684\u7597\u6548\u3002<\/span><\/p>\n

\u7136\u800c, \u7528\u836f<\/span>11\uff5e14 \u4e2a\u6708\u540e, \u60a3\u8005\u4f1a\u4ea7\u751f\u8010\u836f, \u5176\u4e3b\u8981\u539f\u56e0\u662f\u7531\u4e8e<\/span>EGFR \u53d1\u751fT790M\u4e8c\u6b21\u7a81\u53d8, \u589e\u52a0\u4e86\u9776\u6807\u4e0eATP \u7684\u4eb2\u548c\u529b[2]\u3002<\/span><\/p>\n

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

\u4e3a\u4e86\u514b\u670d\u8fd9\u79cd\u8010\u836f\u6027, \u5171\u4ef7TKIs, \u901a\u8fc7\u5171\u4ef7\u4fee<\/span>\u9970EGFR\u7684ATP \u7ed3\u5408\u53e3\u888b\u4e2d\u7684Cys-797 \u6b8b\u57fa, \u4ece\u800c\u514b\u670d<\/span>T790M\u7a81\u53d8[3]\u3002<\/span><\/p>\n

\u5171\u4ef7TKIs \u7684\u4e3b\u8981\u836f\u6548\u56e2\u7279\u5f81\u662f\u901a\u8fc7<\/span>\u836f\u7269\u7ed3\u6784\u7684\u6742\u73af\u9aa8\u67b6\u8fde\u63a5\u758f\u6c34\u57fa\u56e2\u548c\u4eb2\u7535\u6027\u5f39\u5934<\/span>(Michael \u53d7\u4f53)\u3002<\/span><\/p>\n

\u4eb2\u7535\u6027\u5f39\u5934\u4e00\u822c\u91c7\u7528\u4e19\u70ef\u9170\u80fa, \u80fd\u591f<\/span>\u4e0e\u9776\u86cb\u767d\u4e2d\u4fdd\u5b88\u7684, \u6eb6\u5242\u53ef\u53ca\u7684\u534a\u80f1\u6c28\u9178\u6b8b\u57fa\u53d1\u751f\u5171<\/span>\u4ef7\u76f8\u4e92\u4f5c\u7528[4]\u3002<\/span><\/p>\n

\u56fe1 \u662f\u5171\u4ef7TKIs \u4e0eEGFR \u4e2d\u7684\u534a\u80f1\u6c28<\/span>\u9178\u6b8b\u57fa\u53d1\u751f\u5171\u4ef7\u7ed3\u5408\u7684\u793a\u610f\u56fe\u3002<\/span><\/p>\n

\"\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66\"<\/p>\n

<\/span>\u4e0e\u975e\u5171\u4ef7TKIs \u76f8\u6bd4, \u5171\u4ef7TKIs \u5177\u6709\u660e\u663e\u7684\u836f\u7406<\/span>\u5b66\u4f18\u52bf, \u5982\u8f83\u9ad8\u7684\u751f\u5316\u6548\u80fd\u3001\u9009\u62e9\u6027\u9ad8\u3001\u964d\u4f4e\u7ed9\u836f\u5242\u91cf<\/span>\u548c\u7ed9\u836f\u9891\u7387\u3001\u836f\u6548\u5b66\u548c\u836f\u52a8\u5b66\u5206\u79bb, \u5373\u4f7f\u836f\u7269\u6e05\u9664\u7387<\/span>\u9ad8\u4e5f\u80fd\u7ef4\u6301\u6548\u529b\u3001\u80fd\u591f\u9884\u9632\u8010\u836f\u6027\u7684\u4ea7\u751f[5]\u3002<\/span><\/p>\n

\u76ee\u524d, \u7f8e<\/span>\u56fdFDA \u5df2\u6279\u51c6\u4e0a\u5e02\u7684\u5171\u4ef7TKIs \u67096 \u4e2a, \u5305\u62ec\u7b2c2 \u4ee3<\/span>EGFR \u6291\u5236\u5242\u963f\u6cd5\u66ff\u5c3c(afatinib)\u3001\u6765\u90a3\u66ff\u5c3c(neratinib)<\/span>\u548c\u8fbe\u514b\u66ff\u5c3c(dacomitinib), \u7b2c3 \u4ee3EGFR \u6291\u5236\u5242\u5965\u5e0c<\/span>\u66ff\u5c3c(osimertinib)\u3001\u5e03\u9c81\u987f\u916a\u6c28\u9178\u9176(BTK) \u6291\u5236\u5242<\/span>\u4f9d\u9c81\u66ff\u5c3c(ibrutinib) \u548c\u963f\u53ef\u66ff\u5c3c(acalabrutinib)\u3002<\/span><\/p>\n

\u97e9\u56fd<\/span>\u5df2\u6279\u51c6\u7b2c3 \u4ee3EGFR \u6291\u5236\u5242\u5965\u83ab\u66ff\u5c3c(olmutinib) \u4e0a<\/span>\u5e02, \u6211\u56fd\u81ea\u4e3b\u7814\u53d1\u7684\u7b2c2 \u4ee3EGFR \u6291\u5236\u5242\u5421\u54af\u66ff\u5c3c<\/span>(pyrotinib) \u6700\u8fd1\u83b7\u6279\u4e0a\u5e02\u3002\u6b64\u5916, \u8fd8\u6709\u8bb8\u591a\u5171\u4ef7TKIs<\/span>\u5904\u4e8e\u4e34\u5e8a\u7814\u53d1\u9636\u6bb5\u3002<\/span><\/p>\n

\u56fe2 \u5c55\u793a\u4e868 \u4e2a\u5df2\u4e0a\u5e02\u7684\u5171\u4ef7<\/span>TKIs \u7684\u7ed3\u6784\u5f0f\u3002<\/span><\/p>\n

\"\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66\"<\/p>\n

\u672c\u6587\u6982\u8ff0\u4e86\u5171\u4ef7TKIs \u7684\u4f5c\u7528\u673a\u5236\u3001\u836f\u7269\u4ee3\u8c22\u4e0e\u836f\u52a8\u5b66\u3001\u4e0e\u8840\u6d46\u86cb\u767d\u5171\u4ef7\u7ed3\u5408\u7684\u7279\u70b9, \u5e76\u5bf9\u5171\u4ef7TKIs \u7684<\/span>\u836f\u52a8\u5b66\u7814\u7a76\u65b9\u6cd5\u63d0\u51fa\u5c55\u671b\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5171\u4ef7TKIs \u7684\u4f5c\u7528\u673a\u5236<\/strong><\/p>\n<\/section>\n<\/section>\n

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\u5171\u4ef7TKIs \u4e0e\u9776\u86cb\u767d\u7684\u7ed3\u5408\u53ef\u5206\u4e3a\u4e24\u6b65, \u7b2c1 \u6b65\u662f\u836f\u7269\u4e0e\u9776\u86cb\u767d\u7279\u5b9a\u7ed3\u5408\u53e3\u888b\u53d1\u751f\u975e\u5171\u4ef7\u7ed3\u5408, \u5f62\u6210\u975e<\/span>\u5171\u4ef7\u590d\u5408\u7269\u3002<\/span><\/p>\n

\u7b2c2 \u6b65\u662f\u975e\u5171\u4ef7\u590d\u5408\u7269\u4e2d, \u5171\u4ef7TKIs \u7684<\/span>\u5f39\u5934\u4e0e\u9776\u86cb\u767d\u4e2d\u7684\u4eb2\u6838\u6027\u6c28\u57fa\u9178\u6b8b\u57fa\u81ea\u53d1\u5f62\u6210\u5171\u4ef7<\/span>\u952e, \u4ea7\u751f\u4e0d\u53ef\u9006\u7684\u5171\u4ef7\u7ed3\u5408, \u4ece\u800c\u963b\u65ad\u9776\u86cb\u767d\u4e0eATP \u7684<\/span>\u7ed3\u5408[6]\u3002<\/span><\/p>\n

\u56e0\u4e3a\u5171\u4ef7TKIs \u4e0e\u9776\u86cb\u767d\u7684\u5171\u4ef7\u7ed3\u5408\u662f\u4e0d\u53ef\u9006<\/span>\u7684, \u4e14\u916a\u6c28\u9178\u6fc0\u9176\u7684\u5408\u6210\u65f6\u95f4\u8f83\u957f, \u6240\u4ee5\u964d\u4f4e\u4e86\u836f\u7269\u7684<\/span>\u7ed9\u836f\u5242\u91cf\u548c\u7ed9\u836f\u9891\u7387, \u4ece\u800c\u8fdb\u4e00\u6b65\u964d\u4f4e\u4e86\u836f\u7269\u7684\u8131\u9776<\/span>\u6548\u5e94\u548c\u836f\u7269-\u836f\u7269\u76f8\u4e92\u4f5c\u7528\u7684\u53ef\u80fd\u6027[7]\u3002<\/span><\/p>\n

\u867d\u7136\u5171\u4ef7TKIs \u7ed3\u6784\u4e2d\u542b\u6709Michael \u53d7\u4f53, \u4f46\u5176\u4e0e\u53cd\u5e94\u6027\u4ee3\u8c22\u7269\u6709\u7740\u672c\u8d28\u533a\u522b\u3002<\/span><\/p>\n

\u5b83\u4eec\u7684\u533a\u522b\u5728\u4e8e\u540e\u8005\u7684<\/span>\u53cd\u5e94\u6027\u5f88\u5f3a, \u65e0\u9009\u62e9\u6027\u5730\u4e0e\u5927\u91cf\u4eb2\u6838\u6027\u7269\u8d28\u53cd\u5e94\u3002\u800c<\/span>\u5171\u4ef7TKIs \u901a\u8fc7\u7cbe\u5fc3\u8bbe\u8ba1\u540e, \u8c03\u63a7\u5176Michael \u53d7\u4f53\u7684\u53cd<\/span>\u5e94\u6027, \u9009\u62e9\u6027\u5730\u7ed3\u5408\u5230\u7279\u5b9a\u7684\u9776\u86cb\u767d\u3002<\/span><\/p>\n

\u88681[3,8-14]\u603b\u7ed3\u4e867 \u4e2a\u5171\u4ef7TKIs \u7684\u7814\u53d1\u4f01\u4e1a\u3001\u4e0a\u5e02<\/span>\u65f6\u95f4\u3001\u7ed9\u836f\u9014\u5f84\u3001\u9002\u5e94\u8bc1\u3001\u4e34\u5e8a\u7ed9\u836f\u65b9\u6848\u548c\u9776\u70b9\u7684\u4fe1\u606f\u3002<\/span><\/p>\n

\"\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66\"<\/p>\n

\u9664\u4e86\u9776\u70b9\u4fe1\u606f\u5916, \u5176\u4ed6\u4fe1\u606f\u5747\u6765\u6e90\u4e8e\u836f\u54c1\u8bf4\u660e\u4e66\u3002\u5965\u5e0c\u66ff\u5c3c\u662f\u4e0d\u53ef\u9006\u7684EGFR \u6291\u5236\u5242, \u5421\u54af\u66ff\u5c3c\u662f\u4e0d\u53ef\u9006<\/span>\u7684EGFR\/HER-2 \u6291\u5236\u5242, \u963f\u6cd5\u66ff\u5c3c\u3001\u8fbe\u514b\u66ff\u5c3c\u548c\u6765\u90a3\u66ff<\/span>\u5c3c\u662f\u4e0d\u53ef\u9006\u7684EGFR\/HER-2\/HER-4 \u6291\u5236\u5242, \u4f9d\u9c81\u66ff\u5c3c<\/span>\u548c\u963f\u53ef\u66ff\u5c3c\u662f\u4e0d\u53ef\u9006\u7684\u5e03\u9c81\u987f\u6fc0\u9176\u6291\u5236\u5242\u3002<\/span><\/p>\n

\u5bf9\u4e8e\u975e\u5171\u4ef7TKIs \u800c\u8a00, \u9700\u8981\u5c06\u8840\u836f\u6d53\u5ea6\u7ef4\u6301\u5728\u4e00\u5b9a\u6c34\u5e73\u6765\u7ef4\u6301\u836f\u6548\u3002\u800c\u5171\u4ef7TKIs \u4e0e\u9776\u86cb\u767d\u5171\u4ef7\u7ed3\u5408<\/span>\u540e, \u6301\u7eed\u5360\u636e\u9776\u6807\u6d3b\u6027\u4f4d\u70b9, \u4f7f\u5176\u5931\u6d3b, \u9776\u6807\u6d3b\u6027\u7684\u6062<\/span>\u590d\u5468\u671f\u53d6\u51b3\u4e8e\u65b0\u9776\u6807\u5408\u6210\u6240\u9700\u7684\u65f6\u95f4[7]\u3002EGFR \u548c\u5e03<\/span>\u9c81\u987f\u6fc0\u9176\u7684\u5408\u6210\u534a\u8870\u671f\u90fd\u662f16\uff5e24 h[15]\u3002<\/span>\u5bf9\u4e8e\u5171\u4ef7<\/span>TKIs \u800c\u8a00, \u9776\u6807\u5360\u6709\u7387-\u836f\u6548\u52a8\u529b\u5b66\u76f8\u5173\u6027\u53d6\u4ee3\u4e86\u4f20\u7edf\u7684\u836f\u4ee3\u52a8\u529b\u5b66-\u836f\u6548\u52a8\u529b\u5b66(PK\/PD) \u76f8\u5173\u6027\u3002<\/span><\/strong><\/span><\/p>\n

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

\n
\n
\n
\n
\n
\n

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

\n
\n

\u5171\u4ef7TKIs \u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66<\/strong><\/p>\n<\/section>\n<\/section>\n

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

\u88682[16-25]\u603b\u7ed3\u4e867 \u4e2a\u5171\u4ef7TKIs \u7684\u4eba\u4f53\u6e05\u9664\u9014\u5f84\u3002<\/p>\n

\"\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66\"<\/p>\n

\u5421\u54af\u66ff\u5c3c\u548c\u5965\u5e0c\u66ff\u5c3c\u5206\u522b\u662f\u7b2c2 \u4ee3\u548c\u7b2c3 \u4ee3EGFR \u6291<\/span>\u5236\u5242, \u4e24\u8005\u4e0e\u8840\u6d46\u86cb\u767d\u7ed3\u5408\u7684\u53ef\u9006\u6027\u4e0d\u540c\u3002<\/span><\/p>\n

\u672c\u6587\u4ee5\u5965<\/span>\u5e0c\u66ff\u5c3c\u548c\u5421\u54af\u66ff\u5c3c\u4e3a\u4ee3\u8868\u6027\u836f\u7269, \u8be6\u7ec6\u4ecb\u7ecd\u4e86\u8fd9\u4e24\u4e2a<\/span>\u836f\u7269\u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66, \u5e76\u5bf9\u5171\u4ef7TKIs \u7684\u836f\u7269\u76f8\u4e92\u4f5c\u7528<\/span>\u7814\u7a76\u8fdb\u884c\u6c47\u603b\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\uff12.\uff11\u3000\u5965\u5e0c\u66ff\u5c3c<\/strong>\u3000<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5965\u5e0c\u66ff\u5c3c(osimertinib) \u662f\u7b2c3 \u4ee3EGFR \u6291\u5236\u5242, \u5728\u4e00\u9879\u5065\u5eb7\u5fd7\u613f\u8005\u5355\u6b21\u53e3\u670d20 mg<\/span>(0.037 MBq) [14C]-\u5965\u5e0c\u66ff\u5c3c\u7684\u4e34\u5e8a\u8bd5\u9a8c\u4e2d, \u7ed9\u836f84 \u5929<\/span>\u540e, \u653e\u5c04\u6027\u603b\u56de\u6536\u7387\u5360\u7ed9\u836f\u5242\u91cf\u768482%, \u7caa\u548c\u5c3f\u7684\u56de\u6536<\/span>\u7387\u5206\u522b\u662f67.8%\u548c14.2%[23]\u3002<\/span><\/p>\n

\u56fe3 \u5c55\u793a\u4e86\u7269\u8d28\u5e73\u8861\u8bd5<\/span>\u9a8c\u4e2d, \u5965\u5e0c\u66ff\u5c3c\u548c\u8840\u6d46\u603b\u653e\u5c04\u6027\u7684\u836f\u65f6\u66f2\u7ebf\u56fe\u3002<\/span><\/p>\n

\"\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66\"<\/p>\n

\u5965\u5e0c\u66ff\u5c3c\u5728\u4eba\u4f53\u4e2d\u5438\u6536\u826f\u597d(\u81f3\u5c1188%), \u8840\u6d46\u5965\u5e0c\u66ff\u5c3c\u8fbe\u5cf0\u65f6\u95f4(tmax) \u4e3a6 h, \u8840\u6d46\u603b\u653e\u5c04\u6027\u7684tmax \u662f<\/span>144 h[23]\u3002\u5965\u5e0c\u66ff\u5c3c\u7684\u7a33\u6001\u8840\u6d46\u5206\u5e03\u5bb9\u79ef(Vss) \u662f986 L,<\/span>\u8bf4\u660e\u5965\u5e0c\u66ff\u5c3c\u5206\u5e03\u5e7f\u6cdb\u3002\u5965\u5e0c\u66ff\u5c3c\u7684\u8840\u6d46\u86cb\u767d\u7ed3\u5408<\/span>\u7387(\u9884\u6d4b\u503c) \u662f99%, \u5176\u53e3\u670d\u6e05\u9664\u7387(CL\/F) \u662f14.2 L\u3002<\/span><\/p>\n

\u5965\u5e0c\u66ff\u5c3c\u6bcf\u59291 \u6b21, \u572815 \u5929\u540e\u53ef\u8fbe\u7a33\u6001\u3002\u7a33\u6001\u65f6, \u5965\u5e0c\u66ff\u5c3c\u7684AUC\u84c4\u79ef\u6bd4\u662f3\uff5e4[26]\u3002<\/span><\/p>\n

\u5965\u5e0c\u66ff\u5c3c\u7684\u4e3b\u8981\u4ee3\u8c22\u9014\u5f84\u662f\u6c27\u5316\u4ee3\u8c22\u3002\u5728\u7a33\u6001\u6761\u4ef6\u4e0b, \u8840\u6d46\u4e2d\u4e30\u5ea6\u6700\u9ad8\u7684\u4e24\u79cd\u4ee3\u8c22\u7269\u662fAZ5104 \u548c<\/span>AZ7550, \u7ea6\u5360\u68c0\u6d4b\u5230\u7684\u8840\u6d46\u603b\u76f8\u5173\u7269\u8d28\u66b4\u9732\u91cf\u76848%\u548c<\/span>6%\u3002<\/span><\/p>\n

\u5965\u5e0c\u66ff\u5c3c\u3001AZ5104 \u548cAZ7550 \u4e3b\u8981\u7531CYP3A4\/5<\/span>\u50ac\u5316\u4ee3\u8c22(\u5206\u522b\u4e3a54.0%\u300195.1%\u548c99.9%)[23]\u3002<\/span><\/p>\n

\u5965\u5e0c\u66ff\u5c3c\u3001AZ5104 \u548cAZ7550 \u5e73\u5747\u6d88\u9664\u534a\u8870\u671f\u5206<\/span>\u522b\u4e3a61.2\u300155.2 \u548c82.0 h, \u800c\u8840\u6d46\u603b\u653e\u5c04\u6027\u534a\u8870\u671f\u662f<\/span>474 h\u3002<\/span><\/p>\n

\u4f53\u5916\u7814\u7a76\u8868\u660e, \u5965\u5e0c\u66ff\u5c3c\u4e0e\u4eba\u809d\u7ec6\u80de\u3001\u4eba\u8840\u6d46<\/span>\u548c\u4eba\u8840\u6e05\u767d\u86cb\u767d(HSA) \u90fd\u80fd\u53d1\u751f\u5171\u4ef7\u7ed3\u5408\u3002\u8840\u6d46\u603b<\/span>\u653e\u5c04\u6027\u7684\u6d88\u9664\u5ef6\u8fdf\u53ef\u80fd\u662f\u56e0\u4e3a\u5965\u5e0c\u66ff\u5c3c\u4e0e\u4eba\u8840\u6d46\u86cb\u767d<\/span>\u53d1\u751f\u5171\u4ef7\u7ed3\u5408\u3002<\/span><\/p>\n

\u7ed3\u5408\u8840\u6d46\u603b\u653e\u5c04\u6027\u534a\u8870\u671f\u4e0eHSA \u534a<\/span>\u8870\u671f(19\uff5e20 \u5929) \u4e00\u81f4\u7684\u73b0\u8c61, \u8868\u660e\u7ed9\u836f\u540e\u8840\u6d46\u4e2d\u7684\u5927<\/span>\u591a\u6570\u653e\u5c04\u6027\u662f\u4e0d\u53ef\u9006\u5730\u7ed3\u5408\u5230\u8840\u6d46\u86cb\u767d, \u4e14\u4e3b\u8981\u662f\u4e0e<\/span>HSA \u7ed3\u5408[27]\u3002<\/span><\/p>\n

\u5728\u4eba\u4f53\u7269\u8d28\u5e73\u8861\u8bd5\u9a8c\u4e2d, \u5965\u5e0c\u66ff\u5c3c\u3001<\/span>AZ5104 \u548cAZ7550 \u4ec5\u5360\u8840\u6d46\u603b\u653e\u5c04\u6027\u76840.8%\u30010.08%<\/span>\u548c0.07%, \u8bf4\u660e\u4e0e\u8840\u6d46\u86cb\u767d\u5171\u4ef7\u7ed3\u5408\u7684\u836f\u7269\u76f8\u5173\u7269\u8d28<\/span>\u662f\u8840\u6d46\u4e2d\u7684\u4e3b\u8981\u6210\u5206[23]\u3002<\/span><\/p>\n

\u4e0e\u4eba\u809d\u7ec6\u80de\u5b75\u80b2\u65f6, \u5965\u5e0c\u66ff\u5c3c\u751f\u6210\u8c37\u80f1\u7518\u80bd(GSH) \u53ca\u534a\u80f1\u6c28\u9178-\u7518\u6c28\u9178\u7ed3\u5408\u7269\u3002<\/span><\/p>\n

\u800c\u5728\u4eba\u4f53\u7814\u7a76\u4e2d,<\/span>GSH\u7ed3\u5408\u7269\u4ec5\u5360\u6240\u9274\u5b9a\u7684\u4ee3\u8c22\u7269\u7684\u5c0f\u90e8\u5206, \u8868\u660e\u5965\u5e0c<\/span>\u66ff\u5c3c\u5bf9\u86cb\u767d\u7279\u5b9a\u4eb2\u6838\u57fa\u56e2\u7684\u53cd\u5e94\u6027\u9ad8\u4e8eGSH\u3002<\/span><\/p>\n

\u5728\u4eba<\/span>\u4f53ADME \u7814\u7a76\u4e2d, \u4eba\u8840\u6d46\u7684\u653e\u5c04\u6027\u63d0\u53d6\u7387(8%) \u8fdc\u4f4e<\/span>\u4e8e\u7caa\u4fbf(70%), \u8868\u660e\u4e0e\u5965\u5e0c\u66ff\u5c3c\u5171\u4ef7\u7ed3\u5408\u7684\u8840\u6d46\u86cb\u767d<\/span>\u8fdc\u591a\u4e8e\u88ab\u6392\u6cc4\u7684\u86cb\u767d\u8d28\u3002\u7ea6\u670930%\u7684\u5242\u91cf\u4e0e\u86cb\u767d\u8d28<\/span>\u7c7b\u7269\u8d28\u7ed3\u5408, \u88ab\u6392\u6cc4\u5230\u7caa\u4e2d, \u662f\u5965\u5e0c\u66ff\u5c3c\u4e3b\u8981\u7684\u6d88\u9664<\/span>\u9014\u5f84[23]\u3002<\/p>\n

\u5728\u4eba\u4f53\u7269\u8d28\u5e73\u8861\u8bd5\u9a8c\u4e2d, \u5965\u5e0c\u66ff\u5c3c\u5728\u7caa\u548c\u5c3f\u76847\u5929\u7d2f\u79ef\u6392\u6cc4\u91cf\u5206\u522b\u4e3a\u7ed9\u836f\u5242\u91cf\u76841.2%\u548c0.71%, \u8868\u660e<\/span>\u5927\u90e8\u5206\u5965\u5e0c\u66ff\u5c3c\u662f\u901a\u8fc7\u4ee3\u8c22(\u9176\u4fc3\u6216\u5171\u4ef7\u7ed3\u5408\u86cb\u767d<\/span>\u8d28) \u6d88\u9664[23]\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

2.2 \u5421\u54af\u66ff\u5c3c<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5421\u54af\u66ff\u5c3c(pyrotinib) \u662f\u7b2c2 \u4ee3EGFR\/HER-2 \u6291\u5236\u5242\u3002\u5065\u5eb7\u5fd7\u613f\u8005\u5355\u6b21\u53e3\u670d402 mg (5.55<\/span>MBq) [14C]-\u5421\u54af\u66ff\u5c3c\u540e, \u653e\u5c04\u6027\u603b\u56de\u6536\u7387\u662f\u7ed9\u836f\u5242\u91cf<\/span>\u768492.6%, \u7caa\u548c\u5c3f\u7684\u56de\u6536\u7387\u5206\u522b\u662f90.9%\u548c1.72%\u3002<\/span><\/p>\n

\u5421<\/span>\u54af\u66ff\u5c3c\u662f\u7caa\u4fbf\u4e2d\u7684\u4e3b\u8981\u6210\u5206, \u7ea6\u5360\u7caa\u603b\u653e\u5c04\u6027\u7684<\/span>22.4%\u3002<\/span><\/p>\n

\u56fe4 \u662f\u5421\u54af\u66ff\u5c3c\u548c\u8840\u6d46\u603b\u653e\u5c04\u6027\u7684\u836f\u65f6\u66f2\u7ebf<\/span>\u56fe, \u4e8c\u8005\u7684tmax \u5206\u522b\u4e3a5.0 \u548c3.5 h, \u8bf4\u660e\u836f\u7269\u5438\u6536\u8f83<\/span>\u4e3a\u7f13\u6162\u3002\u5355\u6b21\u7ed9\u836f\u540e, \u5421\u54af\u66ff\u5c3c\u7684\u5206\u5e03\u5bb9\u79ef(Vz\/F) \u662f<\/span>8 570 L, \u8bf4\u660e\u836f\u7269\u5206\u5e03\u5e7f\u6cdb[20]\u3002\u5421\u54af\u66ff\u5c3c\u7684\u8840\u6d46\u86cb\u767d<\/span>\u7ed3\u5408\u7387\u662f99.25%, \u5176\u53e3\u670d\u6e05\u9664\u7387(CL\/F) \u662f207 L\u3002<\/span><\/p>\n

\"\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66\"<\/p>\n

\u7a33<\/span>\u6001\u65f6, \u5421\u54af\u66ff\u5c3c\u7684AUC\u7684\u84c4\u79ef\u6bd4\u662f1.22\uff5e1.57[10]\u3002<\/span><\/p>\n

\u5421\u54af\u66ff\u5c3c\u6709\u4e24\u6761\u4ee3\u8c22\u9014\u5f84, \u5206\u522b\u662fO-\u53bb\u70f7\u57fa\u548c\u5421\u54af\u73af\u5355\u6c27\u5316\u5e76\u8131\u6c22, \u4e3b\u8981\u4ee3\u8c22\u9176\u662fCYP3A4[21]\u3002\u4eba\u8840<\/span>\u6d46\u4e2d\u7684\u4e3b\u8981\u6210\u5206\u662f\u5421\u54af\u66ff\u5c3c\u3001SHR150980 (O-\u53bb\u76ae\u8003<\/span>\u6797)\u3001SHR151468 (O-\u53bb\u76ae\u8003\u6797\u5e76\u56db\u6c22\u5421\u54af\u73af\u6c27\u5316\u4e3a\u5185<\/span>\u9170\u80fa)\u3001SHR151136 (\u56db\u6c22\u5421\u54af\u73af\u6c27\u5316\u4e3a\u5185\u9170\u80fa)\u3002<\/span><\/p>\n

\u6839\u636e<\/span>AUC0-\u221e \u6bd4\u503c, \u5b83\u4eec\u5206\u522b\u5360\u8840\u6d46\u603b\u653e\u5c04\u6027\u768410.9%,1.9%\u30011.0%\u548c3.0%\u3002<\/span><\/p>\n

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

\u8840\u6d46\u4e2d\u5927\u7ea6\u670958.3%\u7684\u653e\u5c04\u6027\u4e0e<\/span>\u8840\u6d46\u86cb\u767d\u5171\u4ef7\u7ed3\u5408, \u662f\u8840\u6d46\u4e2d\u7684\u4e3b\u8981\u6210\u5206[20]\u3002\u5421\u54af\u66ff<\/span>\u5c3c\u3001SHR151136\u3001SHR150980\u3001SHR151468 \u548c\u8840\u6d46\u603b\u653e<\/span>\u5c04\u6027\u7684\u534a\u8870\u671f\u5206\u522b\u662f29.3\u30019.75\u300132.2\u300110.4 \u548c47.9 h\u3002<\/span><\/p>\n

\u7ed9\u836f\u540e2 h, \u836f\u7269\u76f8\u5173\u7269\u8d28\u4e0e\u8840\u6d46\u86cb\u767d\u5171\u4ef7\u7ed3\u5408\u90e8\u5206\u5360\u8840\u6d46\u603b\u653e\u5c04\u6027\u768429.3%, \u523048 h \u540e, \u8be5\u6bd4\u4f8b\u589e\u52a0\u81f3<\/span>65.2%\u3002\u5c06\u5421\u54af\u66ff\u5c3c\u4e0e\u4eba\u7a7a\u767d\u8840\u6d46\u572837 \u2103\u5b75\u80b22\u30015\u30018<\/span>\u548c24 h \u540e, \u6837\u54c1\u7684\u63d0\u53d6\u56de\u6536\u7387\u5206\u522b\u964d\u4e3a97.4%\u300191.8%\u3001<\/span>69.6%\u548c46.7%\u3002\u5c06\u5421\u54af\u66ff\u5c3c\u4e0eHSA \u548c\u03b11-\u9178\u6027\u7cd6\u86cb<\/span>\u767d(APG) \u572837 \u2103\u4e0b\u5b75\u80b2, \u4e5f\u53ef\u4ee5\u89c2\u5bdf\u5230\u63d0\u53d6\u56de\u6536\u7387<\/span>\u964d\u4f4e, \u4e14\u5421\u54af\u66ff\u5c3c\u4e3b\u8981\u4e0eHSA\u7ed3\u5408[20]\u3002<\/span><\/p>\n

\u5c06[14C] – \u5421\u54af\u66ff\u5c3c\u4e0e\u8840\u6d46\u5b75\u80b224 h \u540e, \u7528\u76d0\u9178(90 \u2103, 2 h) \u6c34\u89e3, \u7ecf\u653e\u5c04\u6027\u8272\u8c31\u548c\u9ad8\u5206\u8fa8\u8d28\u8c31\u68c0\u6d4b, \u9274<\/span>\u5b9a\u4e86\u4e00\u7cfb\u5217\u5421\u54af\u66ff\u5c3c\u4e0e\u6c28\u57fa\u9178\u52a0\u5408\u7269\u7684\u7ed3\u6784, \u7ed3\u679c\u8868<\/span>\u660e\u5421\u54af\u66ff\u5c3c\u53ef\u4ee5\u5171\u4ef7\u7ed3\u5408\u5230HSA\u7684\u7b2c190 \u4f4d\u8d56\u6c28\u9178\u3002<\/span><\/p>\n

\u8fdb\u4e00\u6b65\u5b9e\u9a8c\u663e\u793a, \u5421\u54af\u66ff\u5c3c\u4e0e\u8840\u6d46\u86cb\u767d\u7684\u5171\u4ef7\u7ed3\u5408\u662f<\/span>\u53ef\u9006\u7684[20]\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

2.3 \u5176\u4ed6\u836f\u7269<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5176\u4ed6\u836f\u7269\u5305\u62ecEGFR\/HER-2\/HER-4\u6291\u5236\u5242\u963f\u6cd5\u66ff\u5c3c\u3001\u6765\u90a3\u66ff\u5c3c\u548c\u8fbe\u514b\u66ff\u5c3c, \u5e03\u9c81\u987f\u6fc0\u9176\u6291<\/span>\u5236\u5242\u4f9d\u9c81\u66ff\u5c3c\u548c\u963f\u53ef\u66ff\u5c3c\u3002<\/span><\/p>\n

\u963f\u6cd5\u66ff\u5c3c\u3001\u6765\u90a3\u66ff\u5c3c\u548c\u8fbe<\/span>\u514b\u66ff\u5c3c\u4eba\u4f53\u7ed9\u836f\u540e, \u5438\u6536\u8f83\u4e3a\u7f13\u6162(tmax \u5206\u522b\u4e3a6\u30017 \u548c<\/span>12 h), \u800c\u5e03\u9c81\u987f\u6fc0\u9176\u6291\u5236\u5242\u4f9d\u9c81\u66ff\u5c3c\u548c\u963f\u53ef\u66ff\u5c3c\u5219\u5438<\/span>\u6536\u8f83\u4e3a\u8fc5\u901f(tmax\u5206\u522b\u4e3a0.52 \u548c0.75 h)\u3002<\/span><\/p>\n

\u9664\u4e86\u963f\u53ef\u66ff\u5c3c<\/span>\u5916, \u5176\u4f594 \u4e2a\u836f\u7269\u90fd\u5177\u6709\u8f83\u9ad8\u7684\u7ec4\u7ec7\u5206\u5e03\u3002<\/span><\/p>\n

5 \u4e2a\u836f\u7269\u7684<\/span>\u8840\u6d46\u86cb\u767d\u7ed3\u5408\u7387\u90fd\u5f88\u9ad8(\u226595%), \u4e14\u4f53\u5916\u5b9e\u9a8c\u8bc1\u660e\u963f\u6cd5<\/span>\u66ff\u5c3c\u548c\u4f9d\u9c81\u66ff\u5c3c\u90fd\u53ef\u4ee5\u4e0eHSA\u5171\u4ef7\u7ed3\u5408[16,22,25,28]\u3002<\/span><\/p>\n

\u5728\u7269\u8d28\u5e73\u8861\u8bd5\u9a8c\u4e2d, \u8840\u6d46\u4e2d\u6709\u5927\u91cf\u7684\u653e\u5c04\u6027\u7ec4\u5206\u4e0d\u80fd\u88ab\u6709\u673a\u6eb6\u5242\u63d0\u53d6\u3002<\/span><\/p>\n

\u8bf4\u660e\u4e0e\u8840\u6d46\u86cb\u767d\u5171\u4ef7\u7ed3\u5408\u7684\u7ec4<\/span>\u5206\u5360\u8840\u6d46\u603b\u653e\u5c04\u6027\u7684\u6bd4\u4f8b\u8f83\u5927\u3002<\/span><\/p>\n

\u5728\u963f\u6cd5\u66ff\u5c3c\u7269\u8d28\u5e73\u8861<\/span>\u8bd5\u9a8c\u4e2d, \u4e0e\u8840\u6d46\u86cb\u767d\u5171\u4ef7\u7ed3\u5408\u7684\u653e\u5c04\u6027\u5360\u8840\u6d46\u603b\u653e\u5c04<\/span>\u6027\u7684\u6bd4\u4f8b\u968f\u7740\u91c7\u6837\u65f6\u95f4\u7684\u589e\u52a0\u800c\u589e\u52a0, \u4ece\u7ed9\u836f\u540e1\uff5e<\/span>2 h \u76847%, \u589e\u52a0\u523072 h \u768448%[16]\u3002<\/span><\/p>\n

\u5bf9\u4e8e\u4f9d\u9c81\u66ff\u5c3c\u800c\u8a00,<\/span>\u4e0e\u8840\u6d46\u86cb\u767d\u5171\u4ef7\u7ed3\u5408\u7684\u653e\u5c04\u6027\u5206\u522b\u5360\u8840\u6d46\u603b\u653e\u5c04\u6027<\/span>AUC0-24 h\u548cAUC0-72 h\u768438%\u548c51%[24]\u3002<\/span><\/p>\n

\u963f\u6cd5\u66ff\u5c3c\u6bcf\u59291 \u6b21, \u57288 \u5929\u540e\u53ef\u8fbe\u7a33\u6001\u3002\u7a33\u6001\u65f6,\u963f\u6cd5\u66ff\u5c3c\u7684Cmax \u548cAUC \u7684\u84c4\u79ef\u6bd4\u5206\u522b\u662f2.0\uff5e2.7 \u548c<\/span>2.5\uff5e3.4[29]\u3002<\/span><\/p>\n

\u8fde\u7eed\u7ed9\u836f6 \u4e2a\u6708\u540e, \u963f\u6cd5\u66ff\u5c3c\u7684\u534a\u8870\u671f\u53ef<\/span>\u8fbe344 h[29]\u3002\u6765\u90a3\u66ff\u5c3c\u591a\u6b21\u7ed9\u836f\u540e, \u7a33\u6001\u65f6\u6765\u90a3\u66ff\u5c3c\u7684<\/span>AUC\u7684\u84c4\u79ef\u6bd4\u662f1.14[30]\u3002<\/span><\/p>\n

\u7a33\u6001\u65f6, \u8fbe\u514b\u66ff\u5c3c\u7684AUC\u84c4<\/span>\u79ef\u6bd4\u662f6.32\uff5e7.37[31]\u3002\u4f9d\u9c81\u66ff\u5c3c\u6bcf\u59291 \u6b21, \u8fde\u7eed\u7ed9\u836f<\/span>\u540e, \u5176AUC\u84c4\u79ef\u6bd4\u4e3a1\uff5e1.6, \u672a\u8868\u73b0\u51fa\u84c4\u79ef[32,33]\u3002\u963f\u53ef<\/span>\u66ff\u5c3c\u4e00\u5929\u4e24\u6b21, \u8fde\u7eed\u7ed9\u836f\u540e\u672a\u8868\u73b0\u51fa\u84c4\u79ef[34]\u3002<\/span><\/p>\n

\u963f\u6cd5\u66ff\u5c3c\u51e0\u4e4e\u4e0d\u7ecfCYP \u9176\u4ee3\u8c22, \u6765\u90a3\u66ff\u5c3c\u3001\u4f9d\u9c81\u66ff\u5c3c\u548c\u963f\u53ef\u66ff\u5c3c\u5219\u4e3b\u8981\u7531CYP3A\u4ee3\u8c22\u3002<\/span><\/p>\n

\u8fbe\u514b\u66ff\u5c3c\u4e3b<\/span>\u8981\u7531CYP2D6 \u4ee3\u8c22, \u4e3b\u8981\u4ee3\u8c22\u9014\u5f84\u4e3a\u6c27\u5316\u4ee3\u8c22\u548c\u7ed3\u5408<\/span>\u4ee3\u8c22\u3002<\/span><\/p>\n

\u5bf9\u4e8e\u4e0d\u53ef\u9006TKIs \u800c\u8a00, \u836f\u7269\u4e3b\u8981\u7ecf\u7531\u7caa\u6392\u6cc4,<\/span>\u5c3f\u6392\u6cc4\u5360\u7684\u6bd4\u4f8b\u8f83\u5c0f\u3002<\/span><\/p>\n

\u4f9d\u9c81\u66ff\u5c3c\u4ee5\u539f\u5f62\u6392\u6cc4\u7684\u91cf\u5f88<\/span>\u5c11, \u80a0\u548c\u809d\u4ee3\u8c22\u751f\u6210\u5927\u91cf\u7684\u6c27\u5316\u7269, \u4e14\u5728\u7caa\u4e2d\u672a\u68c0\u6d4b\u5230<\/span>\u8fd8\u539f\u4ea7\u7269, \u8868\u660e\u4f9d\u9c81\u66ff\u5c3c\u7684\u80c3\u80a0\u9053\u5438\u6536\u5b8c\u5168, \u4e14\u5728\u4f53\u5185<\/span>\u7ecf\u5386\u5e7f\u6cdb\u4ee3\u8c22[24]\u3002<\/span><\/p>\n

\u4f9d\u9c81\u66ff\u5c3c\u548c\u963f\u53ef\u66ff\u5c3c\u7684\u8840\u6d46\u534a\u8870\u671f\u90fd\u5f88\u77ed, \u4f46\u662f\u5176\u836f\u6548\u6301\u7eed\u65f6\u95f4\u957f\u3002<\/span><\/p>\n

\u4f9d\u9c81\u66ff\u5c3c\u7684\u8840\u6d46\u6d88\u9664\u534a\u8870\u671f\u662f<\/span>3.14 h, \u53e3\u670d\u4f9d\u9c81\u66ff\u5c3c420 mg \u540e24 h \u7684\u9776\u6807\u5360\u636e\u7387\u4ecd<\/span>\u5927\u4e8e95%[35]\u3002<\/span><\/p>\n

\u6162\u6027\u6dcb\u5df4\u7ec6\u80de\u767d\u8840\u75c5\u60a3\u8005\u53e3\u670d\u963f\u53ef\u66ff\u5c3c<\/span>100 mg\u540e, \u7ed9\u836f4 h\u540e, \u5e03\u9c81\u987f\u6fc0\u9176\u7684\u5360\u636e\u7387\u53ef\u8fbe99%\uff5e<\/span>100%[36]\u3002<\/span><\/p>\n

\u4e0b\u6b21\u7ed9\u836f\u524d, \u5e03\u9c81\u987f\u6fc0\u9176\u7684\u5360\u636e\u7387\u4ecd\u53ef\u7ef4\u6301<\/span>\u572895%\uff5e97%[34]\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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2.4 \u836f\u7269\u76f8\u4e92\u4f5c\u7528<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u7531\u4e8e\u5927\u591a\u6570\u5171\u4ef7TKIs \u662fCYP3A\u7684\u5e95\u7269, \u56e0\u6b64CYP3A\u7684\u8bf1\u5bfc\u5242\u548c\u6291\u5236\u5242\u4f1a\u5f71\u54cd\u6b64\u7c7b\u836f<\/span>\u7269\u7684\u66b4\u9732\u91cf\u3002<\/span><\/p>\n

\u836f\u7269\u76f8\u4e92\u4f5c\u7528\u7814\u7a76\u4e2d\u5e38\u7528\u7684\u8bf1\u5bfc\u5242\u662f\u5229<\/span>\u798f\u5e73, \u4e34\u5e8a\u8bd5\u9a8c\u65e9\u671f\u4f7f\u7528\u7684\u6291\u5236\u5242\u4e3a\u916e\u5eb7\u5511, \u73b0\u591a\u4e3a\u4f0a<\/span>\u66f2\u5eb7\u5511\u3002\u7531\u4e8e\u916e\u5eb7\u5511\u6216\u4f0a\u66f2\u5eb7\u5511\u6291\u5236\u836f\u7269\u7684\u4ee3\u8c22, \u6240<\/span>\u4ee5\u5bfc\u81f4\u836f\u7269\u7684\u66b4\u9732\u91cf\u589e\u52a0\u3002<\/span><\/p>\n

\u7136\u800c, \u5171\u4ef7TKIs \u66b4\u9732\u91cf\u589e<\/span>\u52a0\u7684\u5e45\u5ea6\u5dee\u522b\u5f88\u5927\u3002\u5982\u4f0a\u66f2\u5eb7\u5511\u4f7f\u5f97\u5965\u5e0c\u66ff\u5c3c\u7684\u8840\u6d46<\/span>\u66b4\u9732\u91cf\u589e\u52a07%, \u800c\u4f7f\u963f\u53ef\u66ff\u5c3c\u7684\u66b4\u9732\u91cf\u589e\u52a0\u52305.1 \u500d\u3002<\/span><\/p>\n

\u5f53\u836f\u7269\u53ea\u7ecf\u5355\u4e00\u9014\u5f84\u4ee3\u8c22\u65f6, \u5176\u53d1\u751f\u836f\u7269\u76f8\u4e92\u4f5c\u7528\u7684\u53ef\u80fd\u6027\u4f1a\u663e\u8457\u589e\u52a0[37]\u3002\u5965\u5e0c\u66ff\u5c3c\u5728\u8840\u6d46\u4e2d\u4e3b\u8981\u4e0e\u8840\u6d46<\/span>\u86cb\u767d\u5171\u4ef7\u7ed3\u5408, \u4ece\u800c\u964d\u4f4e\u4e86CYP \u9176\u5bf9\u5176\u4ee3\u8c22\u7684\u5f71\u54cd\u3002<\/span><\/p>\n

\u4e0e\u5229\u798f\u5e73\u8054\u7528\u65f6, \u5171\u4ef7TKIs \u7684\u66b4\u9732\u91cf\u964d\u4f4e\u3002\u5728\u8fd9\u51e0\u4e2a\u836f\u7269\u4e2d, \u4f9d\u9c81\u66ff\u5c3c\u8840\u6d46\u66b4\u9732\u91cf\u589e\u52a0\u6216\u964d\u4f4e\u7684\u5e45\u5ea6\u6700\u5927,<\/span>\u8fd9\u662f\u56e0\u4e3a\u4f9d\u9c81\u66ff\u5c3c\u7684\u9996\u8fc7\u4ee3\u8c22\u5f88\u5f3a\u3002<\/span><\/p>\n

\u4f0a\u66f2\u5eb7\u5511\u548c\u5229\u798f<\/span>\u5e73\u4e0d\u4ec5\u5f71\u54cd\u4e86\u4f9d\u9c81\u66ff\u5c3c\u7684\u4ee3\u8c22, \u8fd8\u663e\u8457\u5f71\u54cd\u4e86\u5b83\u7684\u751f<\/span>\u7269\u5229\u7528\u5ea6\u3002\u7531\u4e8eCYP3A\u7684\u5f3a\u8bf1\u5bfc\u5242\u6216\u5f3a\u6291\u5236\u5242\u4f1a\u5bfc<\/span>\u81f4\u5171\u4ef7TKIs \u7684\u66b4\u9732\u91cf\u53d1\u751f\u6539\u53d8, \u4e00\u822c\u4e0d\u63a8\u8350\u6216\u907f\u514d\u5c06<\/span>\u8fd9\u4e9b\u836f\u7269\u4e0e\u5171\u4ef7TKIs \u8054\u5408\u4f7f\u7528\u3002<\/span><\/p>\n

\u5982\u679c\u5fc5\u987b\u8054\u7528\u65f6, \u9700<\/span>\u8fdb\u884c\u5242\u91cf\u8c03\u6574\u5e76\u8003\u8651\u8fdb\u884c\u8840\u836f\u6d53\u5ea6\u76d1\u6d4b\u3002<\/span><\/p>\n

\u963f\u6cd5\u66ff\u5c3c\u51e0\u4e4e\u4e0d\u7ecfCYP \u9176\u4ee3\u8c22, \u4f46\u5176\u662f\u8f6c\u8fd0\u4f53Pgp\u7684\u5e95\u7269, \u56e0\u6b64\u5176\u66b4\u9732\u91cf\u53d7P-gp \u8bf1\u5bfc\u5242\u548c\u6291\u5236\u5242\u7684\u5f71<\/span>\u54cd\u3002\u6765\u90a3\u66ff\u5c3c\u662fP-gp \u7684\u6291\u5236\u5242, \u4e0eP-gp \u5e95\u7269\u5730\u9ad8\u8f9b\u5408<\/span>\u7528\u65f6, \u5f71\u54cd\u540e\u8005\u7684\u8840\u6d46\u66b4\u9732\u91cf\u3002<\/span><\/p>\n

\u7531\u4e8e\u6765\u90a3\u66ff\u5c3c\u3001\u8fbe\u514b\u66ff<\/span>\u5c3c\u548c\u963f\u53ef\u66ff\u5c3c\u7684\u6eb6\u89e3\u5ea6\u968fpH\u7684\u589e\u52a0\u800c\u964d\u4f4e, \u6240\u4ee5\u6297\u9178<\/span><\/p>\n

\u836f\u4f1a\u5f71\u54cd\u5b83\u4eec\u7684\u8840\u6d46\u66b4\u9732\u91cf\u3002<\/p>\n

\u88683[38-43]\u6c47\u603b\u4e86\u5df2\u77e5\u7684\u5171\u4ef7TKIs \u7684\u836f\u7269-\u836f\u7269\u76f8\u4e92\u4f5c\u7528\u7814\u7a76, \u90e8\u5206\u6570\u636e\u6765\u6e90<\/span>\u4e8e\u836f\u54c1\u8bf4\u660e\u4e66\u3002<\/span><\/p>\n

\"\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66\"<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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

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\u5171\u4ef7TKIs \u4e0e\u8840\u6d46\u86cb\u767d\u7ed3\u5408\u7684\u7279\u70b9<\/strong><\/p>\n<\/section>\n<\/section>\n

<\/section>\n<\/section>\n<\/section>\n<\/section>\n
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3.1 \u5171\u4ef7TKIs \u5bf9\u86cb\u767d\u7279\u5b9a\u4eb2\u6838\u6027\u57fa\u56e2\u7684\u53cd\u5e94\u6027\u9ad8\u4e8e<\/strong>\u5bf9GSH\u7684\u53cd\u5e94\u6027<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
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\u5171\u4ef7TKIs \u7ed3\u6784\u4e2d\u7684\u4e19\u70ef\u9170\u80fa\u53cd\u5e94\u6027\u4f4e, \u4f46\u5176\u5bf9GSH\u4e2d\u7684\u534a\u80f1\u6c28\u9178\u6b8b\u57fa\u4ecd\u5177\u6709\u4e00\u5b9a\u7684\u4eb2<\/span>\u7535\u6027\u4f5c\u7528\u3002<\/span><\/p>\n

\u5728\u4f53\u5916\u5b9e\u9a8c\u4e2d, \u963f\u6cd5\u66ff\u5c3c\u548c\u6765\u90a3\u66ff\u5c3c\u5bb9\u6613<\/span>\u751f\u6210GSH\u52a0\u5408\u7269[44]\u3002\u4f46\u5728\u4eba\u4f53\u4e2d, \u963f\u6cd5\u66ff\u5c3c\u5728\u8840\u6d46\u4e2d<\/span>\u7684\u4e3b\u8981\u6210\u5206\u662f\u539f\u5f62\u3001\u963f\u6cd5\u66ff\u5c3c\u4e0e\u8840\u6d46\u86cb\u767d\u7684\u52a0\u5408\u7269[16]\u3002<\/span><\/p>\n

\u6765\u90a3\u66ff\u5c3c\u4e3b\u8981\u662f\u7ecfCYP3A4 \u4ecb\u5bfc\u7684\u6c27\u5316\u9014\u5f84\u6e05\u9664[39]\u3002<\/p>\n

\u540c\u6837, \u5bf9\u4e8e\u5965\u5e0c\u66ff\u5c3c\u4e0e\u5421\u54af\u66ff\u5c3c\u800c\u8a00, \u5728\u4eba\u4f53\u4e2d\u751f\u6210\u7684<\/span>GSH\u3001\u534a\u80f1\u6c28\u9178\u6216N-\u4e59\u9170\u534a\u80f1\u6c28\u9178\u7ed3\u5408\u7269\u5360\u5df2\u9274\u5b9a\u7684<\/span>\u4ee3\u8c22\u7269\u7684\u6bd4\u4f8b\u5f88\u5c0f, \u8840\u6d46\u4e2d\u4e3b\u8981\u6210\u5206\u662f\u836f\u7269\u76f8\u5173\u7269\u8d28<\/span>\u4e0e\u8840\u6d46\u86cb\u767d\u7684\u52a0\u5408\u7269[10,20,23]\u3002<\/span><\/p>\n

\u8bf4\u660e\u5728\u4eba\u4f53\u5185, \u5171\u4ef7<\/span>TKIs \u5bf9\u86cb\u767d\u7279\u5b9a\u4eb2\u6838\u6027\u57fa\u56e2\u7684\u53cd\u5e94\u6027\u9ad8\u4e8e\u5bf9GSH\u7684<\/span>\u53cd\u5e94\u6027\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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\n

3.2 \u5171\u4ef7TKIs \u4e0e\u8840\u6d46\u86cb\u767d\u7684\u5171\u4ef7\u7ed3\u5408\u662f\u975e\u9176\u50ac\u5316\u7684\u8fc7\u7a0b, \u5177\u6709\u65f6\u95f4\u4f9d\u8d56\u6027\u548c\u79cd\u5c5e\u7279\u5f02\u6027<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5728\u963f\u6cd5\u66ff\u5c3c\u3001\u4f9d\u9c81\u66ff\u5c3c\u548c\u5421\u54af\u66ff\u5c3c\u4eba\u4f53\u7269\u8d28\u5e73\u8861\u7814\u7a76\u4e2d, \u968f\u7740\u91c7\u6837\u65f6<\/span>\u95f4\u7684\u589e\u52a0, \u653e\u5c04\u6027\u4e0e\u8840\u6d46\u86cb\u767d\u7684\u52a0\u5408\u7269\u5360\u6837\u54c1\u603b\u653e\u5c04<\/span>\u6027\u7684\u6bd4\u4f8b\u589e\u52a0[16,20,24]\u3002<\/span><\/p>\n

\u5c06\u5965\u5e0c\u66ff\u5c3c\u548c\u6765\u90a3\u66ff\u5c3c\u4e0e\u4e0d\u540c<\/span>\u79cd\u5c5e\u7684\u8840\u6d46\u5b75\u80b2\u540e, \u4eba\u8840\u6d46\u63d0\u53d6\u56de\u6536\u7387\u663e\u8457\u4f4e\u4e8e\u5176\u4ed6<\/span>\u79cd\u5c5e\u8840\u6d46\u3002<\/span><\/p>\n

\u7814\u7a76\u8868\u660e, \u6765\u90a3\u66ff\u5c3c\u3001\u963f\u6cd5\u66ff\u5c3c\u3001\u5965\u5e0c\u66ff\u5c3c\u3001<\/span>\u4f9d\u9c81\u66ff\u5c3c\u548c\u5421\u54af\u66ff\u5c3c\u90fd\u53ef\u4ee5\u4e0eHSA \u53d1\u751f\u5171\u4ef7\u7ed3\u5408\u3002<\/span><\/p>\n

HSA \u7531\u5355\u4e00\u80bd\u94fe\u7ec4\u6210, \u542b\u6709585 \u4e2a\u6c28\u57fa\u9178, \u5171\u670935 \u4e2a<\/span>\u534a\u80f1\u6c28\u9178\u6b8b\u57fa, \u5f62\u621017 \u5bf9\u4e8c\u786b\u952e, \u53ea\u6709Cys-34 \u542b\u6709\u6e38<\/span>\u79bb\u5def\u57fa[45]\u3002\u5171\u4ef7TKIs \u4e0e\u8840\u6d46\u86cb\u767d\u5171\u4ef7\u7ed3\u5408\u5177\u6709\u79cd\u5c5e<\/span>\u7279\u5f02\u6027, \u63a8\u6d4b\u662f\u56e0\u4e3a\u4e0d\u540c\u79cd\u5c5e\u7684\u8840\u6e05\u767d\u86cb\u767d\u6c28\u57fa\u9178\u5e8f<\/span>\u5217\u4e0d\u540c, \u5f71\u54cd\u4e86\u7ed3\u5408\u53e3\u888b\u7684\u73af\u5883, \u6539\u53d8\u4e86\u5e95\u7269\u7ed3\u5408\u7684\u65b9<\/span>\u5411, \u6700\u7ec8\u6539\u53d8\u5e95\u7269\u548c\u8840\u6e05\u767d\u86cb\u767d\u7ed3\u5408\u7684\u6027\u8d28\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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\n

3.3  \u5171\u4ef7TKIs \u4e0e\u8840\u6d46\u86cb\u767d\u7ed3\u5408\u7684\u53ef\u9006\u6027<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5171\u4ef7TKIs\u901a\u8fc7Michael \u52a0\u6210\u5171\u4ef7\u7ed3\u5408\u5230\u4eba\u8840\u6d46\u86cb\u767d\u4e0a\u3002<\/span><\/p>\n

\u6709\u6587\u732e<\/span>\u62a5\u9053, \u67d0\u4e9b\u7c7b\u578b\u7684\u5171\u4ef7\u7ed3\u5408, \u5982Michael \u52a0\u6210\u662f\u53ef\u9006<\/span>\u7684[46]\u3002\u4f53\u5916\u5b9e\u9a8c\u8bc1\u660e, \u5421\u54af\u66ff\u5c3c\u548c\u6765\u90a3\u66ff\u5c3c\u4e0e\u8840\u6d46\u86cb<\/span>\u767d\u7684\u5171\u4ef7\u7ed3\u5408\u662f\u53ef\u9006\u7684, \u963f\u6cd5\u66ff\u5c3c\u4e0eHSA\u7684\u5171\u4ef7\u7ed3\u5408<\/span>\u4e5f\u662f\u53ef\u9006\u7684[20,28,47]\u3002<\/span><\/p>\n

\u63a8\u6d4b\u8fbe\u514b\u66ff\u5c3c\u3001\u4f9d\u9c81\u66ff\u5c3c\u4e0e\u8840\u6d46\u86cb<\/span>\u767d\u7684\u7ed3\u5408\u662f\u53ef\u9006\u7684, \u56e0\u4e3a\u5b83\u4eec\u7684\u8840\u6d46\u603b\u653e\u5c04\u6027\u7684\u6d88\u9664<\/span>\u534a\u8870\u671f\u8fdc\u5c0f\u4e8eHSA\u7684\u534a\u8870\u671f\u3002\u5965\u5e0c\u66ff\u5c3c\u5355\u6b21\u7ed9\u836f\u540e,<\/span>\u8840\u6d46\u603b\u653e\u5c04\u6027\u534a\u8870\u671f\u4e0eHSA\u7684\u534a\u8870\u671f\u4e00\u81f4, \u63d0\u793a\u5965\u5e0c<\/span>\u66ff\u5c3c\u4e0eHSA \u7684\u5171\u4ef7\u7ed3\u5408\u662f\u4e0d\u53ef\u9006\u7684\u3002<\/span><\/p>\n

\u836f\u7269\u4e0e\u8840\u6d46\u86cb<\/span>\u767d\u7684\u5171\u4ef7\u7ed3\u5408\u82e5\u662f\u53ef\u9006\u7684, \u90a3\u4e48\u8840\u6d46\u86cb\u767d\u5c31\u53ef\u4ee5\u4f5c\u4e3a<\/span>\u50a8\u5907\u836f\u7269\u7684\u8f7d\u4f53\u3002\u76f8\u53cd, \u4e0e\u8840\u6d46\u86cb\u767d\u7ed3\u5408\u7684\u90e8\u5206\u836f\u7269<\/span>\u5219\u672a\u80fd\u53d1\u6325\u836f\u6548\u4f5c\u7528\u3002\u5171\u4ef7TKIs \u4e0e\u8840\u6d46\u86cb\u767d\u5171\u4ef7\u7ed3<\/span>\u5408\u7684\u53ef\u9006\u6027\u53d7\u54ea\u4e9b\u56e0\u7d20\u5f71\u54cd\u5c1a\u672a\u77e5, \u8fd8\u9700\u8fdb\u4e00\u6b65\u7814\u7a76\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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

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\u7ed3\u8bed<\/strong><\/p>\n<\/section>\n<\/section>\n

<\/section>\n<\/section>\n<\/section>\n<\/section>\n
\n
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\u5171\u4ef7TKIs \u7ed3\u6784\u4e2d\u7684\u4e19\u70ef\u9170\u80fa\u5f39\u5934\u80fd\u4e0e\u8840\u6d46\u86cb\u767d(\u5982\u4eba\u8840\u6e05\u767d\u86cb\u767d) \u53d1\u751f\u5171\u4ef7\u7ed3\u5408, \u4ece\u800c\u5f71\u54cd\u836f\u7269\u7684\u5438<\/span>\u6536\u3001\u5206\u5e03\u3001\u4ee3\u8c22\u548c\u6392\u6cc4\u3002\u5171\u4ef7TKIs \u4e3b\u8981\u7ecf\u7caa\u6392\u6cc4, \u5c3f\u6392<\/span>\u6cc4\u5f88\u5c11\u3002<\/span><\/p>\n

\u5bf9\u4e8e\u8fd9\u7c7b\u836f\u7269\u800c\u8a00, \u809d\u5916\u4ee3\u8c22(\u5982\u4e0e\u8840\u6d46\u86cb<\/span>\u767d\u7ed3\u5408) \u5341\u5206\u91cd\u8981, \u56e0\u6b64\u9700\u91c7\u7528\u653e\u5c04\u6027\u540c\u4f4d\u7d20\u6807\u8bb0\u7684<\/span>\u836f\u7269\u6765\u7814\u7a76\u5176\u4e0e\u8840\u6d46\u86cb\u767d\u7684\u5171\u4ef7\u7ed3\u5408\u3002<\/span><\/p>\n

\u8fd9\u7c7b\u836f\u7269\u5927\u90fd\u7531CYP \u9176\u50ac\u5316\u4ee3\u8c22, \u5f53\u5176\u4e0e\u4e3b\u8981\u4ee3\u8c22\u9176\u7684\u6291\u5236\u5242\u6216\u8bf1<\/span>\u5bfc\u5242\u8054\u7528\u65f6, \u9700\u8981\u53ca\u65f6\u8fdb\u884c\u5242\u91cf\u8c03\u6574\u3002<\/span><\/p>\n

<\/span>\u5171\u4ef7TKIs \u4e0e\u8840\u6d46\u86cb\u767d\u7684\u5171\u4ef7\u7ed3\u5408\u8868\u73b0\u51fa\u79cd\u5c5e\u7279<\/span>\u5f02\u6027, \u56e0\u6b64\u5728\u65e9\u671f\u7814\u7a76\u4e2d\u5e94\u91c7\u7528\u5408\u9002\u7684\u52a8\u7269\u6a21\u578b\u3002<\/span><\/strong><\/span><\/p>\n

\u4f20\u7edf\u7684ADME \u548c\u836f\u4ee3\u52a8\u529b\u5b66(PK) \u7b5b\u9009\u5bf9\u8fd9\u7c7b\u5316\u5408\u7269\u5e76<\/span>\u4e0d\u9002\u7528, \u7814\u7a76\u8005\u66f4\u9700\u8981\u5173\u6ce8\u7684\u662f\u9776\u6807\u7684\u5360\u6709\u7387\u53ca\u5176\u836f<\/span>\u7269\u7684\u9776\u7ec4\u7ec7\u5206\u5e03\u3002\u5728\u7814\u53d1\u8fc7\u7a0b\u4e2d\u5e94\u7b5b\u9009\u5171\u4ef7TKIs \u662f<\/span>\u5426\u4f1a\u4ea7\u751f\u53cd\u5e94\u6027\u4ee3\u8c22\u4ea7\u7269, \u4ee5\u9632\u5171\u4ef7TKIs \u8bbe\u8ba1\u7684\u9009\u62e9<\/span>\u6027\u70f7\u5316\u6027\u8d28\u53d7\u635f\u3002<\/p>\n

\u76ee\u524d, \u5bf9\u5171\u4ef7TKIs \u4e0e\u8131\u9776\u5927\u5206\u5b50\u53cd\u5e94\u53ef\u9006\u6027\u7684\u751f\u7269\u5b66\u540e\u679c\u4e86\u89e3\u5c1a\u5c11\u3002<\/span><\/p>\n

\u76f8\u4fe1\u968f\u7740\u5bf9\u8fd9\u7c7b\u836f<\/span>\u7269\u7684\u6df1\u5165\u7814\u7a76, \u5bf9\u8fd9\u4e9b\u95ee\u9898\u7684\u7406\u89e3\u5c06\u9010\u6e10\u52a0\u6df1\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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

\n
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\"\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66\"<\/p>\n
\n

\u53c2\u8003\u6587\u732e<\/strong><\/p>\n<\/section>\n

\"\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66\"<\/section>\n

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<\/section>\n
<\/section>\n
<\/section>\n<\/section>\n<\/section>\n<\/section>\n
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\u8be6\u89c1\u539f\u6587\uff0c<\/p>\n

\u836f\u5b66\u5b66\u62a5\uff0cActa Pharmaceutica Sinica, 2019, 54(3): 432 \u2212439<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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<\/section>\n
<\/section>\n
<\/section>\n<\/section>\n<\/section>\n
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\u514d\u8d23\u58f0\u660e<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\n
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\u672c\u516c\u4f17\u53f7\u53d1\u5e03\u7684\u6587\u7ae0\u5747\u4e3a\u4fc3\u8fdb\u5236\u836f\u754c\u540c\u884c\u7684\u4ea4\u6d41\u4e0e\u5b66\u4e60\uff1b\u5185\u5bb9\u7531\u5c0f\u7f16\u67e5\u9605\u6587\u732e\u9009\u53d6\uff0c\u6392\u7248\u4e0e\u7f16\u8f91\u4e3a\u539f\u521b\u3002\u5982\u8f6c\u8f7d\uff0c\u8bf7\u6ce8\u660e\u6765\u6e90\u3002<\/p>\n

\u9009\u53d6\u7684\u6587\u7ae0\u5df2\u660e\u786e\u6ce8\u660e\u6765\u6e90\u548c\u4f5c\u8005\uff0c\u7248\u6743\u5f52\u539f\u4f5c\u8005\u6240\u6709\uff0c\u5982\u6d89\u53ca\u4f5c\u54c1\u5185\u5bb9\u3001\u7248\u6743\u6216\u5176\u4ed6\u95ee\u9898\uff0c\u8bf7\u8054\u7cfb\u6211\u4eec\u8fdb\u884c\u5220\u9664\u3002<\/strong><\/p>\n

\u6587\u7ae0\u5185\u5bb9\u4e3a\u4f5c\u8005\u89c2\u70b9\uff0c\u4e0d\u4ee3\u8868\u672c\u516c\u4f17\u53f7\u7acb\u573a\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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<\/section>\n<\/section>\n<\/section>\n
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\u6587\u7ae0\u641c\u7d22<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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\u672c\u516c\u4f17\u53f7\u5f00\u901a\u5f80\u671f\u6587\u7ae0\u4efb\u610f\u641c\u529f\u80fd\u5566
<\/p>\n

\u5728\u516c\u4f17\u53f7\u83dc\u5355\u680f\u4e2d\u8f93\u5165\u201c\u641c\u7d22\u201d\uff0c\u5373\u53ef\u641c\u7d22\u5f80\u671f\u5fae\u4fe1\u5185\u5bb9<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\"\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66\"<\/section>\n<\/section>\n<\/section>\n<\/section>\n


<\/p>\n<\/p><\/div>\n","protected":false},"excerpt":{"rendered":"

\u5171\u4ef7\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\u7684\u4ee3\u8c22\u548c\u836f\u52a8\u5b66 Metabolism and pharmacokinetics of co […]<\/p>\n","protected":false},"author":1,"featured_media":98692,"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\/98691"}],"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=98691"}],"version-history":[{"count":1,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/98691\/revisions"}],"predecessor-version":[{"id":98709,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/98691\/revisions\/98709"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media\/98692"}],"wp:attachment":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media?parent=98691"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/categories?post=98691"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/tags?post=98691"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}