{"id":86601,"date":"2019-04-18T00:00:50","date_gmt":"2019-04-23T03:42:55","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/86601\/"},"modified":"2019-04-23T11:43:03","modified_gmt":"2019-04-23T03:43:03","slug":"92efe93647","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/86601\/","title":{"rendered":"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565"},"content":{"rendered":"
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\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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\u5404\u5927\u5236\u836f\u4f01\u4e1a\u90fd\u5728\u5e7f\u6cdb\u5730\u4f7f\u7528PBPK\u6a21\u578b\uff0c\u539f\u6587\u4f5c\u8005\u901a\u8fc7\u5bf9\u8fd1\u51e0\u5e74\u6587\u732e\u548c\u77e5\u8bc6\u4f53\u7cfb\u7684\u7efc\u5408\u68b3\u7406\uff0c\u7ed3\u5408PBPK\u8d44\u6df1\u5efa\u6a21\u4eba\u5458\u7684\u5b9e\u6218\u7ecf\u9a8c\uff0c\u66f4\u65b0\u548c\u5b8c\u5584\u4e86\u9996\u6b21\u4eba\u4f53PK\u9884\u6d4b\u7684\u5efa\u6a21\u7b56\u7565\u3002\u901a\u8fc7\u5bf9\u8be5\u7b56\u7565\u7684\u5b66\u4e60\u548c\u7406\u89e3\uff0c\u53ef\u66f4\u597d\u5730\u638c\u63e1\u5982\u4f55\u8fd0\u7528PBPK\u5efa\u6a21\u9884\u6d4b\u4eba\u4f53PK\uff0c\u660e\u786e\u5efa\u6a21\u7684\u6b65\u9aa4\u3001\u6d41\u7a0b\u3001\u6240\u9700\u8981\u7684\u6570\u636e\u3001\u6a21\u578b\u7684\u8bc4\u4f30\u7b49\u3002<\/p>\n

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\u5982\u9700\u9ad8\u6e05PDF\u7248\u539f\u6587<\/p>\n

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\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u53c2\u8003\u6587\u732e\u4f5c\u8005\u5355\u4f4d<\/strong><\/p>\n<\/section>\n

\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/section>\n

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Neil A. Miller 1, Micaela B. Reddy 2, Aki T. Heikkinen 3, Viera Lukacova 4, Neil Parrott 5<\/p>\n

1 \u845b\u5170\u7d20\u53f2\u514b\u7814\u53d1\u4e2d\u5fc3(\u82f1\u56fd)\uff0c\u7cfb\u7edf\u5efa\u6a21\u548c\u8f6c\u6362\u751f\u7269\u5b66<\/p>\n

2  Array\u5236\u836f\u516c\u53f8(\u7f8e\u56fd)\uff0c\u4e34\u5e8a\u836f\u7406\u90e8<\/p>\n

3  Admescope\u516c\u53f8(\u82ac\u5170)<\/p>\n

4  Simulations Plus\u516c\u53f8(\u7f8e\u56fd)<\/p>\n

5 \u7f57\u6c0f\u5236\u836f(\u745e\u58eb)\uff0c\u5236\u7a76\u4e0e\u65e9\u671f\u5f00\u53d1\uff0c\u5236\u836f\u79d1\u5b66<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/p>\n
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\u6587\u7ae0\u89e3\u8bfb\u4eba<\/strong><\/p>\n<\/section>\n

\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/section>\n

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\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/p>\n
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\u53c2\u8003\u6587\u732e<\/strong><\/p>\n<\/section>\n

\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/section>\n

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Neil A. Miller, Micaela B. Reddy, Aki T. Heikkinen, et al., Physiologically Based Pharmacokinetic Modelling for First-In Human Predictions:  An UpdatedModel Building Strategy Illustrated with Challenging Industry Case Studies. Clin Pharmacokinet. 2019 Feb 7.   IF: 4.464<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u6458\u8981<\/strong><\/p>\n<\/section>\n

\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/section>\n

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\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66(PBPK)\u5efa\u6a21\u5df2\u7ecf\u5728\u5236\u836f\u4f01\u4e1a\u5f97\u5230\u4e86\u5e7f\u6cdb\u5730\u5e94\u7528\uff0c\u5e76\u5728\u9884\u6d4b\u836f\u7269\u76f8\u4e92\u4f5c\u7528DDI\u65b9\u9762\u5f97\u5230\u4e86\u6cd5\u89c4\u90e8\u95e8\u7684\u8ba4\u53ef\u3002<\/p>\n

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\u4f8b\u5982\uff0c\u5728\u836f\u7269\u53d1\u73b0\u9636\u6bb5PBPK\u5efa\u6a21\u5df2\u7ecf\u5e38\u89c4\u6027\u5730\u7528\u4e8e\u4f53\u5916\u5230\u4f53\u5185\u8f6c\u5316\u4ee5\u53ca\u4e34\u5e8a\u524d\u79cd\u5c5e\u7684\u836f\u4ee3\u52a8\u529b\u5b66\u5efa\u6a21\uff0c\u5e76\u5c06\u9a8c\u8bc1\u540e\u7684\u6a21\u578b\u5e94\u7528\u4e8e\u9884\u6d4b\u9996\u6b21\u4eba\u4f53(FIH) PK\u3002<\/p>\n

\u8be5\u5e94\u7528\u9886\u57df\u4e2d\u4e00\u4e9b\u591a\u4e2a\u884c\u4e1a\u6301\u7eed\u91c7\u7528\u7684\u7b56\u7565\u53ef\u4ee5\u63d0\u9ad8\u5bf9\u5e94\u7528\u65b9\u6cd5\u7684\u4fe1\u5fc3\uff0c\u5e76\u7531\u6b64\u518d\u4fc3\u8fdb\u66f4\u6df1\u5165\u7684\u5b66\u4e60\u4e0e\u4e86\u89e3\u3002\u57fa\u4e8e\u6b64\uff0c\u8be5\u6587\u7ae0\u5c06\u81f4\u529b\u4e8e\u4f18\u5316\u4e4b\u524d\u62a5\u9053\u7684\u57fa\u4e8ePBPK\u5efa\u6a21\u9884\u6d4bFIH PK\u7684\u7b56\u7565\u3002<\/p>\n

\u7ed3\u5408GastroPlus\u2122\u7528\u6237\u7fa4\u6307\u5bfc\u59d4\u5458\u4f1a\u4e2d\u6765\u81ea\u4f17\u591a\u4f01\u4e1a\u79d1\u5b66\u5bb6\u7684\u7ecf\u9a8c\uff0c\u5e76\u5c06\u836f\u7269\u5438\u6536\u3001\u5206\u5e03\u3001\u4ee3\u8c22\u548c\u6392\u6cc4\u7684\u4e00\u4e9b\u6700\u65b0\u77e5\u8bc6\u6574\u5408\u5230\u51b3\u7b56\u6811\u4e2d\u4ee5\u5c55\u793aFIH PK\u9884\u6d4b\u7684\u6bcf\u4e2a\u90e8\u5206\u3002<\/p>\n

\u539f\u6587\u4f5c\u8005\u9605\u8bfb\u4e86\u5f88\u591a\u76f8\u5173\u7684\u79d1\u5b66\u6587\u732e\u4ee5\u63a2\u7d22\u65b0\u7684\u53d1\u73b0\uff0c\u5e76\u6307\u51fa\u4e00\u4e9b\u9700\u8981\u6539\u8fdb\u7684\u5730\u65b9\u3002<\/p>\n

\u6700\u540e\uff0c\u9009\u62e9\u56db\u4e2a\u5177\u6709\u6311\u6218\u6027\u7684\u5316\u5408\u7269\u4f5c\u4e3a\u5e94\u7528\u6848\u4f8b\u4ee5\u9610\u8ff0\u548c\u7a81\u51fa\u65b0\u7b56\u7565\u7684\u4e3b\u8981\u6784\u6210\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5173\u952e\u70b9<\/strong><\/p>\n<\/section>\n

\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/section>\n

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\u7ed3\u5408\u53c2\u6570\u654f\u611f\u6027\u5206\u6790\uff0c\u53ef\u4ee5\u9274\u5b9a\u5f71\u54cd\u7cfb\u7edf\u66b4\u9732\u7684\u5173\u952e\u5316\u5408\u7269\u6027\u8d28\uff0c\u5e76\u6307\u5bfc\u5148\u5bfc\u5316\u5408\u7269\u7684\u4f18\u5316\u3002<\/p>\n

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\u5728\u8fdb\u884c\u8bc4\u4f30\u9884\u6d4bFIH PK\u4e4b\u524d\uff0c\u91c7\u7528\u4e34\u5e8a\u524d\u79cd\u5c5e\u7684\u6570\u636e\u9a8c\u8bc1PBPK\u6a21\u578b\u5bf9\u4e8e\u5efa\u7acb\u53ef\u9760\u53ca\u9884\u6d4b\u51c6\u786e\u6027\u7684\u6a21\u578b\u5341\u5206\u91cd\u8981\uff1b\u4e0d\u786e\u5b9a\u6027\u5206\u6790\u662f\u83b7\u5f97FIH PK\u6700\u5927\u9884\u6d4b\u6570\u503c\u7684\u4e00\u4e2a\u5173\u952e\u56e0\u7d20\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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

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PBPK\u6a21\u578b\u5c06\u673a\u4f53\u751f\u7406\u5b66\u7279\u6027\u548c\u5316\u5408\u7269\u7279\u5b9a\u7684\u6570\u636e\u6574\u5408\u8d77\u6765\u4ee5\u9884\u6d4b\u836f\u7269\u7684\u836f\u4ee3\u52a8\u529b\u5b66\u7279\u5f81\uff0c\u8fde\u540c\u65f6\u95f4-\u8840\u6d46\u6216\u7ec4\u7ec7\u4e2d\u836f\u7269\u6d53\u5ea6\u7684\u53d8\u5316\u3002<\/p>\n

\u5c06PBPK\u6a21\u578b\u8003\u8651\u4e3a\u94fe\u63a5\u673a\u5236\u6027\u5438\u6536\u6a21\u578b(\u5982\u9ad8\u7ea7\u623f\u5ba4\u5438\u6536\u4e0e\u8f6c\u8fd0\u6a21\u578b\uff0cACAT)\u4ee5\u63cf\u8ff0\u7cfb\u7edf\u5904\u7f6e\u7684\u5168\u8eab\u6a21\u578b\u3002PBPK\u5efa\u6a21\u7684\u8d77\u6e90\u53ef\u4ee5\u8ffd\u6eaf\u52301937\u5e74Teorell\u6240\u53d1\u8868\u7684\u6587\u7ae0\uff0c\u4f46\u662fPBPK\u5efa\u6a21\u5e94\u7528\u4e8e\u836f\u7269\u53d1\u73b0\u3001\u5f00\u53d1\u548c\u6cd5\u89c4\u76d1\u7ba1\u57282006\u5e74\u5de6\u53f3\u624d\u5f00\u59cb\u51fa\u73b0\u3002<\/p>\n

US FDA\u548cEMA\u4e5f\u5728\u8fd1\u671f\u53d1\u5e03\u4e86\u5408\u7406\u4f7f\u7528PBPK\u6a21\u578b\u7684\u6307\u5bfc\u6587\u4ef6\uff1b\u6b64\u5916PBPK\u6a21\u578b\u5728\u6307\u5bfc\u5236\u5b9a\u836f\u54c1\u8bf4\u660e\u4e66\u65b9\u9762\u4e5f\u5f97\u5230\u8d8a\u6765\u8d8a\u591a\u7684\u5e94\u7528\u3002<\/p>\n

\u5927\u90e8\u5206\u6cd5\u89c4\u6ce8\u518c\u7533\u8bf7\u8d44\u6599\u4e2d\u6d89\u53ca\u7684PBPK\u5efa\u6a21\u5de5\u4f5c\u4e3b\u8981\u5173\u6ce8\u5728\u836f\u7269\u836f\u7269\u76f8\u4e92\u4f5c\u7528\u548c\u513f\u79d1\u4eba\u7fa4\u7684\u5efa\u6a21\u65b9\u9762\u3002<\/p>\n

\u7136\u800c\uff0c\u8fd1\u5e74\u6765\u5de5\u4e1a\u754c\u5bf9PBPK\u6a21\u578b\u7684\u5e94\u7528\u5df2\u7ecf\u53d1\u751f\u4e86\u5f88\u5927\u7684\u53d8\u5316\uff0c\u6db5\u76d6\u4e86\u5728\u836f\u7269\u53d1\u73b0\u548c\u5f00\u53d1\u9636\u6bb5\u9884\u6d4b\u4e34\u5e8a\u524d\u79cd\u5c5e\u7684\u7279\u5f81\u5230\u4e0d\u540c\u4e34\u5e8a\u4eba\u7fa4\u7684\u53d8\u5f02\u8003\u5bdf\uff0c\u8fd9\u4e5f\u610f\u5473\u7740\u6cd5\u89c4\u5e94\u7528\u4e2d\u7684\u6f5c\u5728\u62d3\u5c55\u3002<\/p>\n

\u57282014\u5e74US FDA\u4e3b\u529e\u7684\u4e00\u573aPBPK\u5efa\u6a21\u7814\u8ba8\u4f1a\u4e0a\uff0c\u53d1\u73b0\u91c7\u7528PBPK\u6a21\u578b\u5bf9\u4e8e\u836f\u7269\u5f00\u53d1\u4eba\u5458\u9884\u6d4bFIH PK\u662f\u975e\u5e38\u6709\u7528\u7684\u3002<\/p>\n

\u56e0\u6b64\uff0cPBPK\u6a21\u578b\u5df2\u7ecf\u8d8a\u6765\u8d8a\u591a\u5730\u7528\u4e8e\u6cd5\u89c4\u6ce8\u518c\u7533\u8bf7\uff0cEMA\u5df2\u5c06\u5176\u4f5c\u4e3a\u8bc4\u4f30\u5065\u5eb7\u5fd7\u613f\u8005\u5408\u9002\u8d77\u59cb\u5242\u91cf\u7684\u4e00\u79cd\u6709\u7528\u5de5\u5177\uff1a\u8981\u6c42\u5c06\u6240\u91c7\u7528\u7684\u65b9\u6cd5(\u5982\u901a\u8fc7PBPK\u5efa\u6a21\u7b49\u65b9\u5f0f)\u3001\u8ba1\u7b97\u51fa\u6765\u7684\u5242\u91cf\u53ca\u5176\u5bf9\u5e94\u7684\u66b4\u9732\u6c34\u5e73\uff0c\u5e94\u5f53\u5305\u542b\u5728\u7814\u7a76\u65b9\u6848\u4e2d\u5e76\u6c47\u603b\u5230\u7814\u7a76\u8005\u624b\u518c\u4e2d\u3002<\/p>\n

\u4f5c\u4e3a\u7cfb\u7edf\u836f\u7406\u5b66\u7684\u4e00\u79cd\u65b9\u6cd5\uff0cPBPK\u6a21\u578b\u53ef\u4ee5\u770b\u4f5c\u662f\u6d1e\u6089\u65b0\u5316\u5b66\u5b9e\u4f53\u6216\u5019\u9009\u5316\u5408\u7269\u836f\u4ee3\u52a8\u529b\u5b66\u6027\u8d28\u7684\u4e00\u4e2a\u65e5\u76ca\u589e\u957f\u7684\u77e5\u8bc6\u5b58\u50a8\u5e93\u3002<\/p>\n

\u5728FIH\u8bd5\u9a8c\u4e4b\u524d\u5e94\u7528PBPK\u5efa\u6a21\u9884\u6d4b\u836f\u7269\u7684\u4e34\u5e8aPK\uff0c\u8fd9\u5bf9\u4e34\u5e8a\u524d\u836f\u7269\u7684\u5f00\u53d1\u975e\u5e38\u6709\u7528\u3002<\/p>\n

\u6765\u81eaJones\u7b49\u53d1\u8868\u7684\u6709\u5f71\u54cd\u529b\u6587\u7ae0\uff0c\u6307\u51fa\u5148\u7528\u4e34\u5e8a\u524d\u79cd\u5c5e\u5bf9PBPK\u6a21\u578b\u7684\u9884\u6d4b\u80fd\u529b\u8fdb\u884c\u9a8c\u8bc1\uff0c\u7136\u540e\u9884\u6d4b\u4eba\u4f53PK\uff0c\u8be5\u65b9\u5f0f\u8981\u4f18\u4e8e\u91c7\u7528\u7ecf\u9a8c\u65b9\u6cd5\u9884\u6d4b\u4eba\u4f53\u7279\u5f81\u3002<\/p>\n

\u6b64\u540e\uff0c\u6765\u81ea\u5236\u836f\u4f01\u4e1a\u7684\u4e00\u4e9b\u6587\u732e\u4e5f\u8bc1\u660e\u4e86PBPK\u6a21\u578b\u5728\u8fd9\u65b9\u9762\u5e94\u7528\u7684\u4f18\u8d8a\u6027\uff0c\u800c\u4e14\u5f88\u591a\u4e2d\u5927\u578b\u5236\u836f\u4f01\u4e1a\u73b0\u5728\u5df2\u5e38\u89c4\u6027\u5730\u4f7f\u7528\u4e86\u8be5\u65b9\u6cd5\u3002<\/p>\n

\u539f\u6587\u4f5c\u8005\u66f4\u65b0\u4e86Jones\u7b49\u4eba\u62a5\u9053\u7684\u5efa\u6a21\u7b56\u7565\uff0c\u5c06\u4e00\u4e9b\u65b0\u7684\u77e5\u8bc6\u548c\u9644\u52a0\u7684\u6d41\u7a0b\u56fe\u5305\u542b\u5230FIH\u9884\u6d4b\u7684\u6bcf\u4e2a\u90e8\u5206\u91cc\u3002\u5c3d\u7ba1\u4e00\u4e9b\u4fe1\u606f\u662f\u4ec5\u5305\u62ec\u5728GastroPlus\u4e2d\u4e14\u6240\u5217\u4e3e\u7684\u6848\u4f8b\u4e5f\u662f\u91c7\u7528GastroPlus\u642d\u5efa\u7684\uff0c\u4f46\u6240\u5448\u73b0\u7684\u5f88\u591a\u4fe1\u606f\u90fd\u53ef\u4ee5\u9002\u7528\u4e8e\u5e38\u89c4\u7684PBPK\u5efa\u6a21\u3002<\/p>\n

\u8be5\u6587\u7ae0\u6240\u63d0\u51fa\u7684\u65b0\u7b56\u7565\u662f\u7ed3\u5408\u5bf9\u5927\u91cf\u6587\u732e\u7684\u7efc\u5408\u5ba1\u9605\u4ee5\u53ca\u6574\u5408\u4f5c\u8005(\u4ed6\u4eec\u90fd\u662fPBPK\u5efa\u6a21\u4e13\u5bb6\u548cGastroPlus\u7528\u6237\u7fa4\u6307\u5bfc\u59d4\u5458\u4f1a\u7684\u6210\u5458)\u7684\u77e5\u8bc6\u548c\u7ecf\u9a8c\u8fdb\u884c\u66f4\u65b0\u5f97\u5230\u7684\u3002\u8be5\u6587\u7ae0\u4ee5\u5168\u65b0\u7684\u89c6\u89d2\u53bb\u4fee\u8ba2\u73b0\u6709\u7684\u9884\u6d4b\u7b56\u7565\uff0c\u5305\u62ec\u5728\u5b9e\u9a8c\u5f00\u5c55\u524d\u4f7f\u7528\u5b9a\u91cf\u7ed3\u6784-\u6027\u8d28\u5173\u7cfb(QSPR)\u6a21\u578b\u7684\u9884\u6d4b\u6570\u636e\u4f5c\u4e3aPBPK\u6a21\u578b\u7684\u8f93\u5165\u53c2\u6570\uff1b\u5c06\u6700\u65b0\u7684\u5438\u6536\u3001\u5206\u5e03\u3001\u4ee3\u8c22\u548c\u6392\u6cc4(ADME)\u77e5\u8bc6\u6574\u5408\u5230\u63a8\u8350\u7684\u51b3\u7b56\u6811\u4e2d\uff1b\u5e76\u7740\u91cd\u8bf4\u660e\u6a21\u578b\u9884\u6d4b\u4e2d\u4e0d\u786e\u5b9a\u8003\u8651\u7684\u91cd\u8981\u6027\u3002<\/p>\n

\u6240\u5217\u4e3e\u7684\u5e94\u7528\u6848\u4f8b\u5f3a\u5316\u4e86\u7b56\u7565\u7684\u5e94\u7528\uff0c\u4ee5\u53ca\u6709\u6311\u6218\u6027\u7684\u5316\u5408\u7269\u6a21\u578b\u4e2d\u67d0\u4e9b\u8f93\u5165\u53c2\u6570(\u5982\u5168\u8840\u8840\u6d46\u6d53\u5ea6\u6bd4\uff0cRBP)\u548c\u6a21\u578b\u7ec4\u6210(\u5982\u7ec4\u7ec7\u7684\u6a21\u578b)\u7684\u91cd\u8981\u6027\u3002<\/p>\n

\u539f\u6587\u4f5c\u8005\u575a\u4fe1\u7ed3\u5408\u591a\u4e2a\u4f01\u4e1a\u6700\u4f18\u79c0\u7684\u5b9e\u8df5\u548c\u7ecf\u9a8c\u66f4\u65b0\u7684\u9884\u6d4bFIH\u7684\u7edf\u4e00\u7b56\u7565\uff0c\u53ef\u4ee5\u63d0\u9ad8\u6cd5\u89c4\u76d1\u7ba1\u90e8\u95e8\u5728\u8be5\u65b9\u9762\u5e94\u7528\u7684\u4fe1\u5fc3\u3002<\/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

\u6a21\u578b\u642d\u5efa\u7b56\u7565<\/strong><\/p>\n<\/section>\n<\/section>\n

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

PBPK\u6a21\u578b\u9700\u8c03\u8282\u5f88\u591a\u53c2\u6570\uff0c\u8fd9\u4f7f\u6a21\u578b\u8f83\u4e3a\u590d\u6742\uff0c\u8fd9\u5f71\u54cd\u4e86\u7edf\u4e00\u6a21\u578b\u642d\u5efa\u7b56\u7565\u548c\u6700\u4f73\u5b9e\u8df5\u6307\u5357\u7684\u60c5\u51b5\u3002<\/p>\n

PBPK\u6a21\u578b\u9700\u8981\u5f88\u591a\u5b66\u79d1\u3001\u4e0d\u540c\u80cc\u666f\u79d1\u5b66\u5bb6\u7684\u914d\u5408\uff0c\u56e0\u6b64\u4e00\u79cd\u53ef\u4ee5\u8986\u76d6\u5f88\u591a\u60c5\u5f62\u7684\u5e38\u89c4\u65b9\u6cd5\u53ef\u4ee5\u5f88\u597d\u5730\u4fc3\u8fdb\u76d1\u7ba1\u8bc4\u4f30\u3002<\/p>\n

\u8fde\u540c\u7edf\u4e00\u7684\u6a21\u578b\u7b56\u7565\uff0c\u91c7\u7528\u4e00\u81f4\u7684\u751f\u7406\u5b66\u53c2\u6570\u548c\u6bd4\u653e\u56e0\u5b50\u4ee5\u4f7f\u5f97\u5404\u4e2a\u5316\u5408\u7269\u540c\u7b49\u6bd4\u5bf9\uff0c\u6b64\u5916\u4e00\u4e9b\u516c\u5f0f\u4f1a\u91c7\u7528\u5185\u90e8\u7684\u89c4\u5219\u4ee5\u786e\u4fdd\u6a21\u578b\u7684\u4e00\u81f4\u6027\u3002<\/p>\n

\u6bd4\u5982\u4e00\u4e9b\u5173\u952e\u53c2\u6570\u7684\u53ef\u80fd\u8303\u56f4\uff0c\u6587\u732e\u62a5\u9053\u4e86\u5927\u9f20\u809d\u8840\u6d41\u91cf\u7684\u6570\u503c\u670947.2\uff0c55.2\u548c80 mL\/min\/kg\u7b49\u3002<\/p>\n

GastroPlus\u5185\u5efa\u7684PBPK\u6a21\u578b\u6db5\u76d6\u4e86\u79cd\u5c5e\u7279\u5f02\u6027\u7684\u751f\u7406\u5b66\u53c2\u6570\u548c\u6bd4\u653e\u56e0\u5b50\u7b49\u6570\u636e\uff0c\u4ee5\u786e\u4fdd\u6a21\u578b\u7684\u4e00\u81f4\u6027\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

2.1 \u91c7\u7528QSPR\u548cPBPK\u6a21\u578b\u8bc4\u4f30\u5316\u5408\u7269<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5c3d\u7ba1PBPK\u6a21\u578b\u9700\u8981\u5316\u5408\u7269\u5927\u91cf\u7684\u76f8\u5173\u53c2\u6570\uff0c\u4f46\u5f88\u591a\u6570\u636e\u53ef\u4ee5\u91c7\u7528QSPR\u6a21\u578b\u9884\u6d4b\u5f97\u5230\uff0c\u8fd9\u4f7f\u5f97\u5728\u5b9e\u9a8c\u5f00\u5c55\u524d\u7684\u65e9\u671f\u836f\u7269\u53d1\u73b0\u9636\u6bb5\u4fbf\u80fd\u4f7f\u7528PBPK\u6a21\u578b\uff0c\u7279\u522b\u5bf9\u865a\u62df\u5316\u5408\u7269\u7684\u5efa\u6a21\u975e\u5e38\u6709\u7528\u3002<\/p>\n

\u5c3d\u7ba1\u91c7\u7528\u5f88\u591a\u57fa\u4e8e\u7ed3\u6784\u5f0f\u9884\u6d4b\u7684\u53c2\u6570\u6240\u8fdb\u884cPK\u51c6\u786e\u9884\u6d4b\u662f\u6709\u53ef\u80fd\u7684\uff0c\u4f46\u76ee\u524d\u8fd8\u6ca1\u6709\u901a\u8fc7\u6bcf\u4e00\u4e2a\u5316\u5b66\u7cfb\u5217\u7684\u5316\u5408\u7269\u8fdb\u884c\u6709\u6548\u9a8c\u8bc1\u548c\u8bc4\u4ef7\u3002<\/p>\n

\u65e9\u671f\u6a21\u62df\u4e2d\u8054\u5408QSPR\u6a21\u578b\u7684\u9884\u6d4b\u7ed3\u679c(\u5982\u8102\u6eb6\u6027\u3001\u9178\u78b1\u6027\u3001\u6e05\u9664\u7387\u3001\u6eb6\u89e3\u5ea6\u3001\u6e17\u900f\u6027\u3001\u7ea2\u7ec6\u80de\u548c\u8840\u6d46\u86cb\u767d\u7684\u7ed3\u5408\u7b49)\u548cPBPK\u6a21\u578b\u53ef\u4ee5\u9274\u5b9a\u53d8\u5f02\u548c\u4e3b\u8981\u654f\u611f\u7684\u53c2\u6570\uff1b\u80fd\u591f\u53ca\u65f6\u5f00\u5c55\u76f8\u5e94\u5b9e\u9a8c\u4ee5\u53ca\u4f18\u5148\u5206\u914d\u7b26\u5408\u76ee\u6807(fit for purpose)\u7684\u8d44\u6e90\uff0c\u4ee5\u652f\u6301\u6a21\u578b\u7684\u642d\u5efa\u548c\u4e34\u5e8a\u524d\u6570\u636e\u7684\u9a8c\u8bc1\u3002<\/p>\n

PBPK\u6a21\u578b\u5728\u4ec5\u6709\u5c11\u91cf\u6570\u636e\u7684\u836f\u7269\u53d1\u73b0\u9636\u6bb5\u5df2\u7ecf\u5f97\u5230\u4e86\u6210\u529f\u7684\u5e94\u7528\u3002<\/p>\n

\u968f\u7740\u5316\u5408\u7269\u7814\u53d1\u7684\u8fdb\u5c55\uff0c\u6a21\u578b\u53ef\u4ee5\u91c7\u7528\u66f4\u591a\u7684\u5b9e\u9a8c\u6570\u636e\u8fdb\u884c\u5b8c\u5584\u66f4\u65b0\u3002\u7136\u540e\u5728\u8fdb\u884cFIH\u9884\u6d4b\u65f6\uff0c\u7ecf\u5e38\u9700\u8981\u4e00\u6574\u5957\u5b8c\u5584\u7684\u5b9e\u9a8c\u6d4b\u91cf\u6570\u636e\u4f5c\u4e3a\u6a21\u578b\u8f93\u5165\u53c2\u6570\u3002<\/p>\n

\u6a21\u578b\u9884\u6d4b\u7684\u51c6\u786e\u6027\u53ef\u4ee5\u901a\u8fc7\u8003\u8651\u4e34\u5e8a\u524d\u6570\u636e\u3001\u8868\u5f81\u5df2\u9274\u5b9a\u7684\u6570\u636e\u5dee\u5f02\u548c\u9a8c\u8bc1\u4e34\u5e8a\u524d\u7684PBPK\u6a21\u578b\u7b49\u65b9\u5f0f\u8fdb\u884c\u4f18\u5316\u548c\u63d0\u9ad8\u3002<\/p>\n

\u5728\u5c06QSPR\u6a21\u578b\u9884\u6d4b\u53c2\u6570\u6574\u5408\u5230PBPK\u6a21\u578b(Fig. 1)\u540e\u53ef\u4ee5\u6d1e\u6089\u5316\u5408\u7269\u7684\u6027\u8d28\u4ee5\u53ca\u9700\u8981\u589e\u52a0\u7684\u5b9e\u9a8c\u3002\u4f53\u5185\u4f5c\u7528\u4ee5\u53ca\u5316\u5408\u7269\u6027\u8d28\u548c\u751f\u7406\u5b66\u6846\u67b6\u95f4\u7684\u76f8\u4e92\u5f71\u54cd\uff0c\u53ef\u4ee5\u901a\u8fc7\u53c2\u6570\u654f\u611f\u6027\u5206\u6790(PSA)\u8fdb\u884c\u7814\u7a76\u3002<\/p>\n

\u4f8b\u5982\u5bf9\u4e8e\u4e00\u4e2a\u78b1\u6027\u5316\u5408\u7269\uff0c\u836f\u7269\u5728\u5c0f\u80a0\u4e2d\u7684\u6c89\u6dc0\u4ee5\u53ca\u548c\u7ec4\u7ec7\u4e2d\u9178\u6027\u78f7\u8102\u7684\u7ed3\u5408\u53ef\u80fd\u975e\u5e38\u5173\u952e\u3002\u8fd9\u4e9b\u53ef\u4ee5\u901a\u8fc7\u8bc4\u4f30\u6240\u9884\u6d4b\u7684\u53c2\u6570(\u5982\u6c89\u6dc0\u901f\u7387\u3001\u80a0\u9053\u6eb6\u89e3\u5ea6\u548cBPR\uff0c\u5176\u4e2dBPR\u53c8\u5c06\u5f71\u54cd\u7ec4\u7ec7\u7ed3\u5408\u548c\u7a33\u6001\u5206\u5e03\u4f53\u79ef\uff0cVss)\u5bf9\u9884\u6d4b\u7684\u8840\u6d46\u836f\u7269\u6d53\u5ea6-\u65f6\u95f4\u66f2\u7ebf\u7684\u5f71\u54cd\u8fdb\u884c\u63a2\u5bfb\u548c\u8bc4\u4ef7\u3002<\/p>\n

\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/p>\n

Fig. 1 \u91c7\u7528<\/span>QSPR\u548c<\/span>PBPK\u5efa\u6a21\u4ece\u7ed3\u6784\u5f0f\u51fa\u53d1\u8bc4\u4f30\u5316\u5408\u7269\uff1a<\/span><\/strong><\/span><\/strong>BCS-\u751f\u7269\u836f\u5242\u5b66\u5206\u7c7b\u7cfb\u7edf\uff1b<\/span><\/strong><\/span><\/strong>BDDCS-\u751f\u7269\u836f\u5242\u5b66\u836f\u7269\u5904\u7f6e\u5206\u7c7b\u7cfb\u7edf\uff1b<\/span><\/strong><\/span><\/strong>BPR-\u5168\u8840\u8840\u6d46\u836f\u7269\u6d53\u5ea6\u6bd4\uff1b<\/span><\/strong><\/span><\/strong>Dn-\u6eb6\u51fa\u6307\u6570<\/span>(\u836f\u7269\u5728\u5c0f\u80a0\u4e2d\u7684\u8f6c\u8fd0\u65f6\u95f4\u4e0e\u7406\u60f3\u7684\u6eb6\u51fa\u65f6\u95f4\u4e4b\u6bd4<\/span>)\uff1b<\/span><\/strong><\/span><\/strong>ECCS-\u6269\u5c55\u6e05\u9664\u5206\u7c7b\u7cfb\u7edf\uff1b<\/span><\/strong><\/span><\/strong>Fup-\u8840\u6d46\u6e38\u79bb\u836f\u7269\u5206\u6570\uff1b<\/span><\/strong><\/span><\/strong>GI-\u80c3\u80a0\u9053\uff1b<\/span><\/strong><\/span><\/strong>IVIVE-\u4f53\u5916\u4f53\u5185\u5916\u63a8\u3002<\/span><\/strong><\/span><\/span><\/p>\n

\u5bf9\u8054\u5408ADMET Predictor\u2122\u548cGastroPlus\u8f6f\u4ef6\u5f00\u5c55\u7684\u521d\u59cbQSPR\u548cPBPK\u6a21\u578b\u8fdb\u884c\u8bc4\u4f30\uff0c\u53ef\u4ee5\u8ba9\u5efa\u6a21\u4eba\u5458\u53d1\u73b0\u6240\u642d\u5efa\u7684\u7279\u5b9a\u836f\u7269\u5206\u5b50\u6a21\u578b\u7684\u4e3b\u8981\u6311\u6218\u3002<\/p>\n

\u56e0\u6b64\uff0c\u5982\u679c\u5316\u5408\u7269\u88ab\u9884\u6d4b\u4e3a\u751f\u7269\u836f\u5242\u5b66\u5206\u7c7b\u7cfb\u7edf(BCS)\u7684I\u548cII\u7c7b\uff0c\u90a3\u4e48\u673a\u5236\u6027\u53e3\u670d\u5438\u6536\u6a21\u578b\u7684\u9884\u6d4b\u53ef\u80fd\u5c31\u8f83\u4e3a\u7b80\u5355\u4e86\uff0c\u76f8\u53cd\u5bf9\u4e8eIII\u548cIV\u7c7b\u5316\u5408\u7269\u53ef\u80fd\u5c31\u6709\u4e00\u5b9a\u7684\u6311\u6218\u6027\u3002<\/p>\n

\u6b64\u5916\uff0c\u6269\u5c55\u6e05\u9664\u5206\u7c7b\u7cfb\u7edf(ECCS)\u7684\u6846\u67b6\u4e5f\u5728\u6700\u8fd1\u6574\u5408\u5230\u4e86ADMET Predictor\u2122 Version 9.0\u6a21\u578b\u4e2d\uff0c\u5b83\u53ef\u4ee5\u9884\u6d4b\u4e00\u4e2a\u5316\u5408\u7269\u662f\u5426\u4e3b\u8981\u7ecf\u80be\u810f\u6392\u6cc4\u6e05\u9664\uff0c\u4ee5\u53ca\u809d\u810f\u8f6c\u8fd0\u4f53\u662f\u5426\u5f71\u54cd\u6e05\u9664\u7b49\u3002<\/p>\n

\u5982\u679c\u9884\u6d4b\u5316\u5408\u7269\u4e3b\u8981\u7ecf\u7ec6\u80de\u8272\u7d20P450 (CYP) 3A4\u809d\u810f\u4ee3\u8c22\u7684\u65b9\u5f0f\u6e05\u9664\uff0c\u90a3\u4e48\u80a0\u9053\u4ee3\u8c22\u5bf9\u53e3\u670d\u751f\u7269\u5229\u7528\u5ea6\u7684\u4f5c\u7528\u5c31\u9700\u8981\u8003\u8651\u5230\u6a21\u578b\u4e2d\uff0c\u4e14\u65e9\u671f\u5c31\u9700\u8981\u5f00\u5c55\u4ee3\u8c22\u8868\u578b\u7684\u5b9e\u9a8c\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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2.2 <\/span>\u4ee3\u8c22\u548c\u6e05\u9664<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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\n

PBPK\u5efa\u6a21\u9700\u8981\u5b9a\u91cf\u7406\u89e3\u836f\u7269\u6e05\u9664\u7684\u4e3b\u8981\u673a\u5236\uff0cFig. 2\u4ee3\u8868\u4e86\u8003\u8651\u836f\u7269\u6e05\u9664\u9014\u5f84\u7684\u7b56\u7565\u3002<\/p>\n

\u5728\u65e9\u671f\u53d1\u73b0\u9636\u6bb5\u9884\u6d4b\u5316\u5408\u7269\u7684\u6e05\u9664\u7387\u4f9d\u7136\u5177\u6709\u4e00\u5b9a\u7684\u6311\u6218\uff0c\u7136\u800c\u8fd1\u671f\u7814\u7a76\u8bc1\u660e\u91c7\u7528\u540c\u4e00\u7cfb\u5217\u5316\u5408\u7269\u642d\u5efa\u7684QSPR\u6a21\u578b\u8fdb\u884c\u9884\u6d4b\u76f8\u5bf9\u8f83\u6210\u529f\u3002<\/p>\n

\u6269\u5c55\u6e05\u9664\u5206\u7c7b\u7cfb\u7edf\u662f\u4e00\u4e2a\u975e\u5e38\u6709\u7528\u7684\u53c2\u8003\u4fe1\u606f\uff0c\u5982\u679c\u9884\u6d4b\u4e00\u4e2a\u5316\u5408\u7269\u4e3b\u8981\u7ecf\u809d\u810f\u4ee3\u8c22\u7684\u65b9\u5f0f\u6d88\u9664\uff0c\u90a3\u4e48\u5f53\u4e34\u5e8a\u524d\u79cd\u5c5e\u80fd\u591f\u5efa\u7acb\u8d77\u4f53\u5916\u4f53\u5185\u5916\u63a8(IVIVE)\u8f6c\u5316\u65b9\u6cd5\u540e\uff0c\u8fdb\u4e00\u6b65\u51c6\u786e\u9884\u6d4b\u4eba\u4f53\u6e05\u9664\u7684\u4fe1\u5fc3\u662f\u975e\u5e38\u9ad8\u7684\u3002\u5bf9\u4e8e\u4e3b\u8981\u7ecfCYP\u9176\u4ee3\u8c22\u7684\u5316\u5408\u7269\uff0c\u5efa\u7acb\u8d77\u4e00\u4e2a\u6210\u529fIVIVE\u65b9\u6cd5\u7684\u53ef\u80fd\u6027\u8fd8\u662f\u6bd4\u8f83\u9ad8\u7684\uff1b\u4f46\u5bf9\u4e8e\u975eCYP\u9176\u4ee3\u8c22\u7684\u60c5\u51b5\uff0c\u5373\u4f7f\u5e38\u91c7\u7528\u809d\u7ec6\u80de\u6a21\u578b\u8fdb\u884c\u5b9a\u91cf\u8868\u8fbe\uff0c\u4e5f\u4f9d\u7136\u5b58\u5728\u5f88\u591a\u6311\u6218\u3002<\/p>\n

\u6269\u5c55\u6e05\u9664\u5206\u7c7b\u7cfb\u7edf\u53ef\u4ee5\u6807\u8bc6\u51fa\u6d89\u53ca\u4e3b\u52a8\u6444\u53d6\u7684\u809d\u810f\u6e05\u9664\uff0c\u8fd9\u79cd\u60c5\u51b5\u4e0b\u9009\u62e9\u809d\u7ec6\u80de\u6a21\u578b\u6d4b\u5b9a\u52a8\u529b\u5b66\u6570\u636e\u662f\u8f83\u4e3a\u6709\u7528\u7684\uff0c\u4e14\u4eba\u4f53\u6e05\u9664\u7387\u7684\u9884\u6d4b\u53ef\u4ee5\u91c7\u7528\u8de8\u79cd\u5c5e\u7684\u7ecf\u9a8c\u6bd4\u653e\u56e0\u5b50\u8fdb\u884c\u6539\u5584\u3002<\/p>\n

\u5f88\u591a\u5148\u8fdb\u7684\u809d\u7ec6\u80de\u6a21\u578b\u5df2\u7ecf\u5728\u63a2\u5bfb\u6d89\u53ca\u66f4\u590d\u6742\u60c5\u51b5\u7684IVIVE\u6570\u636e\u8f6c\u6362\u3002\u6d89\u53ca\u4e3b\u52a8\u8f6c\u8fd0\u7684\u80be\u810f\u3001\u80c6\u6c41\u6392\u6cc4\u6e05\u9664\u4ece\u4f53\u5916\u6570\u636e\u8fdb\u884c\u673a\u5236\u6027\u7684\u9884\u6d4b\u4e5f\u5177\u6709\u4e00\u5b9a\u7684\u6311\u6218\uff0c\u901a\u5e38\u9884\u6d4b\u6d89\u53ca\u8f6c\u8fd0\u4f53\u4f5c\u7528\u7684\u5206\u5b50\u5728\u4eba\u4f53\u7684PK\u662f\u6709\u4e00\u5b9a\u7684\u56f0\u96be\uff0c\u56e0\u4e3a\u8be5\u60c5\u51b5\u4e0b\u836f\u7269\u7684\u5438\u6536\u3001\u5206\u5e03\u548c\u6d88\u9664\u90fd\u53d7\u5176\u5f71\u54cd\u3002<\/p>\n

\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/p>\n

Fig. 2 PBPK\u6a21\u578b\u6e05\u9664\u7387\u7684\u9884\u6d4b\u7b56\u7565\uff1a<\/span><\/strong>CLR<\/sub>–\u80be\u810f\u6e05\u9664\u7387\uff1b<\/span><\/strong>CLR,u<\/sub>–\u6e38\u79bb\u7684\u80be\u810f\u6e05\u9664\u7387\uff1b<\/span><\/strong>ECCS-\u6269\u5c55\u6e05\u9664\u5206\u7c7b\u7cfb\u7edf\uff1b<\/span><\/strong>fup-\u6e38\u79bb\u836f\u7269\u5206\u6570\uff1b<\/span><\/strong>GFR-\u80be\u5c0f\u7403\u6ee4\u8fc7\u7387\uff1b<\/span><\/strong>IVIVE-\u4f53\u5916\u4f53\u5185\u5916\u63a8<\/span><\/strong><\/span><\/span><\/strong><\/p>\n

\u4e0d\u8fc7\u73b0\u5728\u4e5f\u6709\u4e00\u4e9b\u4ee4\u4eba\u632f\u594b\u7684\u884c\u4e1a\u53d1\u5c55\uff1a\u6bd4\u5982\u5bf9\u4e8e\u80be\u810f\u5206\u6ccc\uff0c\u6709\u6587\u732e\u62a5\u9053\u91c7\u7528\u6d4b\u5b9a\u6709\u673a\u9634\u79bb\u5b50\u8f6c\u67d3\u7684\u4eba\u80da\u80ce\u80be\u7ec6\u80de\u7684\u52a8\u529b\u5b66\u6570\u636e\u6210\u529f\u9884\u6d4b\u4e8631\u4e2a\u7ed3\u6784\u591a\u6837\u836f\u7269\u7684\u80be\u810f\u6e05\u9664\uff0c\u867d\u7136\u9700\u8981\u91c7\u7528\u5927\u91cf\u836f\u7269\u6570\u636e\u96c6\u9a8c\u8bc1\u80be\u5c0f\u7ba1\u88ab\u52a8\u91cd\u5438\u6536\u7684\u673a\u5236\u6027\u6a21\u578b\uff1b\u5bf9\u4e8e\u809d\u810f\u6e05\u9664\uff0c\u8fd1\u671f\u6709\u6587\u732e\u8868\u660e\u6765\u81ea\u4e09\u660e\u6cbb\u6784\u578b\u57f9\u517b\u809d\u7ec6\u80de\u7684\u6570\u636e\u5e76\u4fdd\u6301\u76f8\u540c\u7684IVIVE\u65b9\u6cd5\uff0c\u53ef\u4ee5\u51c6\u786e\u9884\u6d4b17\u4e2a\u7ed3\u6784\u4e0d\u540c\u836f\u7269\u7684\u4eba\u4f53\u6e05\u9664\u7387\u3002<\/p>\n

\u6b64\u5916\uff0c\u91c7\u7528\u4f53\u5916\u548c\u4f53\u5185\u8f6c\u8fd0\u4f53\u8868\u8fbe\u6570\u636e\uff0c\u901a\u8fc7\u4e09\u660e\u6cbb\u6784\u578b\u7684\u673a\u5236\u6027IVIVE\u6a21\u578b\u53ef\u4ee5\u6539\u5584\u745e\u8212\u4f10\u4ed6\u6c40\u5927\u9f20\u6e05\u9664\u7387\u7684\u9884\u6d4b\u7ed3\u679c\u3002<\/p>\n

\u7814\u7a76\u8fd8\u62a5\u9053\u4e86\u7334\u5b50\u662f\u4e00\u4e2a\u975e\u5e38\u6709\u4ef7\u503c\u7684\u6a21\u578b\u53ef\u4ee5\u9a8c\u8bc1\u53d7\u8f6c\u8fd0\u4f53\u4f5c\u7528\u5316\u5408\u7269\u7684\u809d\u810f\u5904\u7f6e\u7279\u5f81\uff0c\u7279\u522b\u662f\u6709\u673a\u9633\u79bb\u5b50\u591a\u80bd\u8f6c\u8fd0\u86cb\u767d\u7684\u5e95\u7269\u3002\u73b0\u5728\u5df2\u7ecf\u5b58\u5728\u4e00\u4e9b\u5305\u542b\u4ece\u4f53\u5916\u7814\u7a76\u8868\u5f81\u4ee3\u8c22\u9176\u548c\u8f6c\u8fd0\u4f53\u52a8\u529b\u5b66\u7684\u590d\u6742PBPK\u6a21\u578b\u6848\u4f8b\uff0c\u8fd9\u4e5f\u5c06\u5728\u4eca\u540e\u7684\u6a21\u578b\u53d1\u5c55\u4e2d\u5e38\u5e38\u51fa\u73b0\u3002<\/p>\n

\u4e0d\u8003\u8651\u836f\u7269\u673a\u5236\u65f6\uff0c\u5982\u679c\u4e34\u5e8a\u524d\u79cd\u5c5e\u6e05\u9664\u7387\u7684\u9884\u6d4b\u7ed3\u679c\u5f97\u4ee5\u9a8c\u8bc1\uff0c\u90a3\u4e48\u5c06\u589e\u5f3a\u6210\u529f\u9884\u6d4bFIH PK\u7684\u4fe1\u5fc3\u3002<\/p>\n

\u5982\u679cIVIVE\u65b9\u6cd5\u5728\u4e34\u5e8a\u524d\u79cd\u5c5e\u4e0d\u80fd\u6210\u529f\u5efa\u7acb\uff0c\u90a3\u4e48\u9700\u8981\u91c7\u7528\u7ecf\u9a8c\u6027\u6bd4\u653e\u56e0\u5b50\u9884\u6d4b\u4eba\u4f53\u6e05\u9664(\u89c14.1\u7ae0\u8282\u7684Compound 1)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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2.3 \u5206\u5e03<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\n

\u7406\u89e3\u836f\u7269\u7684\u7ec4\u7ec7\u5206\u5e03\u5bf9\u4e8ePBPK\u5efa\u6a21\u662f\u5fc5\u9700\u7684\uff0c\u4e14\u80fd\u901a\u8fc7\u4e00\u4e9b\u673a\u5236\u6027\u516c\u5f0f\u8f85\u52a9\u52a0\u6df1\u8ba4\u8bc6\u3002\u56fe3\u8868\u793a\u4e86PBPK\u6a21\u578b\u8003\u5bdf\u5206\u5e03\u7ec4\u6210\u7684\u7b56\u7565\u3002<\/p>\n

GastroPlus\u5185\u5efa\u4e86Lukacova Kp (\u7ec4\u7ec7-\u8840\u6d46\u5206\u914d\u7cfb\u6570)\u8ba1\u7b97\u65b9\u6cd5\u8ba1\u7b97\u836f\u7269\u7684\u5206\u5e03\uff0c\u8be5\u65b9\u6cd5\u662f\u5efa\u7acb\u5728\u524d\u4eba\u5de5\u4f5c\u57fa\u7840\u4e0a\u7684\uff0c\u4f46\u540c\u65f6\u4e5f\u91c7\u7528\u4e86\u5176\u5b83\u65b9\u6cd5\u3002\u65e0\u8bba\u4f7f\u7528\u54ea\u79cd\u65b9\u6cd5\uff0c\u90fd\u5c06\u7528\u5230\u4f53\u5916\u5b9e\u6d4b\u7684log P, pKa, fup\u548cBPR\u7b49\u53c2\u6570\uff0c\u4ee5\u53ca\u5efa\u8bae\u901a\u8fc7\u4e34\u5e8a\u524d\u79cd\u5c5e\u8fdb\u884c\u9a8c\u8bc1\u4ee5\u4fdd\u8bc1\u9884\u6d4b\u7684\u51c6\u786e\u6027(Fig. 3)\u3002<\/p>\n

\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/p>\n

Fig. 3 PBPK\u6a21\u578b\u5206\u5e03\u4f53\u79ef\u7684\u9884\u6d4b\u7b56\u7565\uff1a<\/span><\/span><\/span><\/span>BPR-\u5168\u8840<\/span>\/\u8840\u6d46\u6d53\u5ea6\u6bd4\uff1b<\/span><\/span><\/span><\/span>fup-\u8840\u6d46\u6e38\u79bb\u836f\u7269\u5206\u6570\uff1b<\/span><\/span><\/span><\/span>Kp-\u7ec4\u7ec7<\/span>–\u8840\u6d46\u5206\u914d\u7cfb\u6570\uff1b<\/span><\/span><\/span><\/span>SpecPStc-\u6bcf\u6beb\u5347\u7ec4\u7ec7\u7ec6\u80de\u4f53\u79ef\u7684\u7279\u5b9a\u4f53\u5185\u6269\u6563\u6e05\u9664\u7387\u3002<\/span><\/span><\/strong><\/span><\/p>\n

\u5bf9\u4e8e\u88ab\u52a8\u6269\u6563\u5360\u4e3b\u5bfc\u4f5c\u7528\u7684\u5206\u5b50\uff0c\u5206\u5e03\u7684\u9884\u6d4b\u5e38\u91c7\u7528\u6807\u51c6\u7684\u8840\u6d41\u704c\u6ce8\u7ec4\u7ec7\u6a21\u578b\u3002<\/p>\n

\u5982Compound 2 (4.2\u7ae0\u8282)\u7684\u6848\u4f8b\uff0c\u91cd\u70b9\u7a81\u51fa\u4e86\u5b9e\u6d4bBPR\u7684\u6570\u636e\u5bf9\u4e8e\u9884\u6d4b\u78b1\u6027\u5316\u5408\u7269Vss\u7684\u5f71\u54cd\u3002<\/p>\n

\u7136\u800c\uff0c\u5bf9\u4e8e\u5927\u5206\u5b50\u4e14\u4ee5\u8f83\u6162\u7684\u901f\u5ea6\u88ab\u52a8\u6269\u6563\u900f\u8fc7\u7ec4\u7ec7\u7ec6\u80de\u819c(\u59824.4\u7ae0\u8282\u7684Compound 4)\uff0c\u53ef\u80fd\u9700\u8981\u91c7\u7528\u819c\u6e17\u900f\u9650\u901f\u578b\u7684\u7ec4\u7ec7\u5206\u5e03\uff0c\u4e14\u8fd8\u5305\u542b\u4e86\u6f5c\u5728\u7684\u8f6c\u8fd0\u4f53\u52a8\u529b\u5b66\u3002\u5728\u5176\u5b83\u7684\u4e00\u4e9b\u6848\u4f8b\u4e2d\uff0c\u8f93\u5165\u7684\u5b9e\u6d4bBPR\u6570\u636e\u6839\u636e\u89c2\u6d4b\u7684Vss\u8fdb\u884c\u4e86\u7ecf\u9a8c\u6027\u7684\u8c03\u6574\u3002\u8c03\u6574BPR\u4ee5\u8003\u8651\u78b1\u6027\u4eb2\u8102\u6027\u5316\u5408\u7269\u53d7\u78f7\u916f\u7c7b\u7ed3\u5408\u4ee5\u53ca\u6eb6\u9176\u4f53\u6355\u83b7\u4f5c\u7528\uff0c\u76ee\u524d\u8fd8\u57fa\u672c\u662f\u6839\u636e\u7ecf\u9a8c\u8fdb\u884c\u62df\u5408\uff0c\u4ee5\u8bf4\u660e\u542b\u6709\u5927\u91cf\u6eb6\u9176\u4f53\u7684\u7ec4\u7ec7\u4e2d\u5176\u89c2\u6d4b\u5230\u9178\u6027\u78f7\u916f\u7684\u542b\u91cf\u5f88\u9ad8\u3002<\/p>\n

\u6574\u5408\u516c\u5f0f\u4ee5\u63cf\u8ff0\u6eb6\u9176\u4f53\u5bf9Kp\u9884\u6d4b\u6570\u503c\u7684\u8d21\u732e\uff0c\u53ef\u80fd\u4f1a\u5305\u542b\u5728\u5c06\u6765\u7248\u672c\u7684GastroPlus\u4e2d\u3002<\/p>\n

\u5f53\u7ec4\u7ec7\u5206\u914d\u65b9\u7a0b\u4e0d\u80fd\u5f88\u597d\u9884\u6d4b\u65f6\uff0c\u5b9a\u91cf\u5168\u8eab\u653e\u5c04\u81ea\u663e\u5f71\u6280\u672f\u7684\u6570\u636e(\u82e5\u80fd\u53cd\u6620\u6bcd\u836f\u53d8\u5316)\u53ef\u4ee5\u7528\u4f5c\u4f30\u7b97Kp\u7684\u6570\u503c\uff0c\u4ee5\u53ca\u4ece\u5927\u9f20\u6570\u636e\u51c6\u786e\u5730\u9884\u6d4b\u4eba\u4f53PK\u3002<\/p>\n

\u6b64\u5916\uff0c\u53ef\u5047\u8bbe\u6e38\u79bbKp\u662f\u4e00\u81f4\u7684\uff0c\u4e14\u8003\u8651\u79cd\u5c5e\u95f4\u8840\u6d46\u86cb\u767d\u7684\u5dee\u5f02\uff0c\u53ef\u4ece\u52a8\u7269\u7684Kp\u6570\u636e\u653e\u5927\u5230\u4eba\u4f53\u6570\u636e\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

2.4 \u53e3\u670d\u5438\u6536<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u7531\u4e8e\u53e3\u670d\u5438\u6536\u662f\u4e00\u4e2a\u591a\u79cd\u56e0\u7d20\u4ea4\u4e92\u7684\u8fc7\u7a0b\uff0c\u56e0\u6b64\u4e34\u5e8a\u524d\u9884\u6d4b\u7ed3\u679c\u7684\u9a8c\u8bc1\u5bf9\u4e8e\u5efa\u7acb\u53ef\u9760\u7684FIH\u6a21\u578b\u975e\u5e38\u91cd\u8981\u3002\u5728\u5efa\u7acb\u4e34\u5e8a\u524d\u79cd\u5c5ePBPK\u6a21\u578b\u65f6\uff0c\u4e3a\u63d0\u9ad8\u53e3\u670d\u6a21\u578b\u7684\u9884\u6d4b\u51c6\u786e\u6027\uff0c\u4e00\u822c\u9700\u8981\u7528\u5230\u9759\u8109\u7ed9\u836f\u7684PK\u6570\u636e\u4ee5\u786e\u4fdd\u5904\u7f6e\u6a21\u578b\u7684\u51c6\u786e\u642d\u5efa\uff1b\u8be5\u6570\u636e\u53ef\u4ee5\u5e2e\u52a9\u6821\u6b63\u7cfb\u7edf\u7684PBPK\u6a21\u578b\u6216\u8005\u4f18\u5316\u7ecf\u5178\u623f\u5ba4\u6a21\u578b\u3002<\/p>\n

\u4e5f\u9700\u8981\u6d4b\u5b9a\u751f\u7406\u4ecb\u8d28\u4e2d\u7684\u6eb6\u89e3\u5ea6\u6570\u636e\uff0c\u9664\u975e\u4eb2\u6c34\u6027\u6eb6\u89e3\u5ea6\u975e\u5e38\u5927\u53ef\u4ee5\u4fdd\u8bc1\u5316\u5408\u7269\u5b8c\u5168\u3001\u5feb\u901f\u7684\u6eb6\u51fa\u3002\u5bf9\u4e8eFIH\u9884\u6d4b\uff0c\u63a8\u8350\u91c7\u7528\u6765\u81ea\u540c\u4e00\u4e2a\u5b9e\u9a8c\u4f53\u7cfb\u7684\u4f53\u5916\u6e17\u900f\u6570\u636e\u4e0e\u4f53\u5185\u6e17\u900f\u5efa\u7acb\u8f6c\u5316\u5173\u7cfb\u3002\u56fe4\u63d0\u4f9b\u4e86\u8bc4\u4f30\u4e0d\u540c\u56e0\u7d20\u5f71\u54cd\u53e3\u670d\u5438\u6536\u7684\u6846\u67b6\u3002<\/p>\n

\u5bf9\u4e8e\u4eb2\u8102\u6027\u5316\u5408\u7269\uff0c\u5438\u6536\u53ef\u80fd\u5bf9\u80c6\u9178\u76d0\u589e\u6eb6\u56e0\u5b50(BSSR)\u6bd4\u8f83\u654f\u611f\uff0c\u56e0\u6b64\u53ef\u4ee5\u91c7\u7528\u6a21\u62df\u7a7a\u8179\u72b6\u6001\u7684\u80a0\u6db2(FaSSIF)\u4ee5\u53ca\u6a21\u62df\u9971\u8179\u72b6\u6001\u7684\u80a0\u6db2(FeSSIF)\u7684\u6eb6\u89e3\u5ea6\u9884\u6d4bBSSR\uff0c\u8be5\u6570\u636e\u53c8\u53ef\u7528\u4e8e\u4e34\u5e8a\u524d\u79cd\u5c5e\u53e3\u670d\u6570\u636e\u7684\u9a8c\u8bc1\u6216\u4f18\u5316\u3002<\/p>\n

\u5f53\u524dGastroPlus\u6a21\u578b\u5728\u80c6\u9178\u76d0\u5bf9\u4e8e\u4f53\u5185\u6eb6\u89e3\u589e\u6eb6\u4f5c\u7528\u65b9\u9762\u7684\u8003\u8651\uff0c\u57fa\u4e8e\u4e86\u7a7a\u8179\u4e0e\u7a7a\u8179\u4ecb\u8d28\u4e2d\u80c6\u9178\u76d0\u6d53\u5ea6\u5bf9\u4eb2\u6c34\u6027\u6eb6\u89e3\u5ea6\u7684\u76f8\u5bf9\u6539\u53d8\u8fdb\u884c\u4f53\u73b0\u7684\u3002\u5982\u679c\u91c7\u7528FaSSIF\u6216FeSSIF\u4f30\u7b97\u7684BSSR\u6570\u503c\u4e0d\u4e00\u6837\uff0c\u90a3\u4e48\u53ef\u80fd\u6697\u793a\u53ef\u80fd\u8fd8\u9700\u5c06\u7b80\u5355\u80c6\u9178\u76d0\u589e\u6eb6\u4f5c\u7528\u4e4b\u5916\u7684\u56e0\u7d20\u8003\u8651\u8fdb\u6765\u3002\u5728\u4e00\u4e9b\u6848\u4f8b\u4e2d\uff0c\u4e34\u5e8a\u524d\u79cd\u5c5e\u4f53\u5185\u6a21\u578b\u7684\u9a8c\u8bc1\u53ef\u4ee5\u7528\u4e8e\u4f30\u7b97BSSR\u6570\u503c\u7684\u76f8\u5173\u6027\u3002<\/p>\n

\u6240\u4f7f\u7528\u7684\u57fa\u4e8e\u4e34\u5e8a\u524d\u79cd\u5c5e\u7684\u5efa\u6a21\u53bb\u5377\u79ef\u5f97\u5230\u7684\u751f\u7269\u4f53\u76f8\u5173\u6eb6\u89e3\u5ea6\uff0c\u53ef\u4ee5\u7ecf\u8fc7\u4e00\u7cfb\u5217\u5316\u5408\u7269(\u5305\u62ec\u6240\u6709BCS\u6216BDDCS\u7684\u5206\u7c7b)\u7684\u51c6\u786e\u9884\u6d4b\u5f97\u4ee5\u652f\u6301\u3002<\/span><\/p>\n

\u901a\u5e38\uff0c\u751f\u7406\u5b66\u53c2\u6570\u662f\u4e0d\u9700\u8981\u4f18\u5316\u7684\uff0c\u5efa\u8bae\u91c7\u7528GastroPlus ACAT\u6a21\u578b\u9ed8\u8ba4\u7684\u6570\u636e\uff0c\u867d\u7136\u6709\u65f6\u4f1a\u53d1\u751f\u4e00\u4e9b\u5fae\u5c0f\u7684\u8c03\u6574\u3002<\/p>\n

\u4f8b\u5982\uff0c\u6709\u4e9b\u6a21\u578b\u53c2\u6570(\u5982\u80c3\u80a0\u9053\u6db2\u4f53\u7684\u603b\u91cf)\u5177\u6709\u660e\u663e\u7684\u4e0d\u786e\u5b9a\u6027\u3002<\/p>\n

\u5bf9\u4e8eCompound 1 (BCS Class II)\uff0c\u5305\u62ec\u5df2\u77e5\u7684\u80c3\u80a0\u9053\u6db2\u4f53\u4f53\u79ef\u7684\u53d8\u5f02\u6027\u4ee5\u53ca\u5b9e\u9645\u5236\u5242\u7c92\u5f84\u6570\u636e\uff0c\u5bf9\u4e8e\u53e3\u670d\u5438\u6536\u9884\u6d4b\u90fd\u975e\u5e38\u91cd\u8981\u3002\u5176\u5b83\u7684\u4e00\u4e9b\u6848\u4f8b\u4e5f\u5c55\u793a\u4e86\u8fdb\u884c\u9002\u5f53\u7684ACAT\u6a21\u578b\u53c2\u6570\u8c03\u6574\uff0c\u5305\u62ec\u80c3\u8f6c\u8fd0\u65f6\u95f4(\u8be5\u53c2\u6570\u5c55\u73b0\u4e86\u968f\u65f6\u95f4\u7684\u53d8\u5f02)\uff0c\u80c3\u4e2dpH (\u5982\u540c\u65f6\u670d\u7528\u8d28\u5b50\u6cf5\u6291\u5236\u5242\u7684\u75c5\u4eba)\u4ee5\u53ca\u4fee\u6b63\u5185\u5efa\u7684\u79cd\u5c5e\u95f4\u6709\u6548\u6e17\u900f\u6027\u8f6c\u5316\u5173\u7cfb\u7b49\u3002<\/p>\n

\u5c3d\u7ba1\u62a5\u9053\u4e86\u4e00\u4e9b\u8c03\u6574\u79cd\u5c5e\u7279\u5f02\u6027\u5438\u6536\u653e\u5927\u56e0\u5b50\u7684\u7814\u7a76\uff0c\u4f46\u7ec6\u81f4\u5730\u8bc4\u4f30\u3001\u9a8c\u8bc1\u79cd\u5c5e\u7279\u5f02\u6027\u7684ACAT\u6a21\u578b\u7684\u5de5\u4f5c\u672a\u89c1\u62a5\u9053\u3002\u8fd9\u4e9b\u7814\u7a76\u91c7\u7528\u72d7\u7406\u8bba\u7684\u8868\u9762\u79ef-\u4f53\u79ef\u6bd4\u503c(SA\/V)\u6a21\u578b\u4ee5\u53ca\u4f7f\u7528\u8bbe\u7f6e\u7ed3\u80a0\u6e17\u900f\u901f\u7387\u4e0e\u4eba\u5c0f\u80a0\u76f8\u540c\u7684Opt-logD SA\/V Version 6.1\u6a21\u578b\u3002<\/p>\n

\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/p>\n

Fig. 4 PBPK<\/span>\u6a21\u578b\u53e3\u670d\u5438\u6536\u9884\u6d4b\u7684\u7b56\u7565\uff1a<\/span><\/span>ASF-<\/span>\u5438\u6536\u653e\u5927\u56e0\u5b50\uff1b<\/span><\/span>BSSR-<\/span>\u80c6\u9178\u76d0\u589e\u6eb6\u56e0\u5b50\uff1b<\/span><\/span>MPT-<\/span>\u5e73\u5747\u6c89\u6dc0\u65f6\u95f4\uff1b<\/span>\u5176\u5b83\u8fc7\u7a0b<\/span>–<\/span>\u8f6c\u8fd0\u4f53\uff0c\u53ef\u4ee5\u901a\u8fc7\u7b80\u5355\u7684\u65b9\u6cd5<\/span>(<\/span>\u5982\u57fa\u4e8e\u4e34\u5e8a\u524d\u89c2\u6d4b\u7ed3\u679c\u6216\u4f53\u5916\u6570\u636e\u8c03\u6574\u6e17\u900f\u6027<\/span>)<\/span>\u5230\u66f4\u590d\u6742\u7684\u65b9\u6cd5<\/span>(<\/span>\u8bbe\u7f6e\u7279\u5b9a\u8f6c\u8fd0\u4f53\u7684\u4f5c\u7528<\/span>)<\/span>\u5c06\u5916\u6392\u8f6c\u8fd0\u4f53\u7684\u4f5c\u7528\u6574\u5408\u5230<\/span>GastroPlus<\/span>\u6a21\u578b\u4e2d\u3002<\/span><\/strong><\/span><\/p>\n

\u7406\u60f3\u72b6\u6001\uff0c\u4e34\u5e8a\u524d\u53e3\u670dPK\u6570\u636e\u5e94\u5f53\u8986\u76d6\u4eba\u4f53\u76f8\u5173\u7684\u7ed9\u836f\u5242\u91cf\u548c\u5242\u578b\uff0c\u8fdb\u800c\u4f7f\u5f97\u9a8c\u8bc1\u7684\u76f8\u5173\u5242\u91cf\u4e0b\u7684\u5236\u5242\u6a21\u578b\u6709\u8f83\u9ad8\u7684\u53ef\u4fe1\u5ea6\u3002\u4e34\u5e8a\u524d\u79cd\u5c5e\u53ef\u4ee5\u7814\u7a76\u98df\u7269\u6548\u5e94\uff0c\u5e76\u6307\u5bfc\u4eba\u4f53PK\u7684\u9884\u6d4b\u3002<\/p>\n

\u5982\u679c\u4e00\u4e2a\u5316\u5408\u7269\u53d1\u73b0\u5728\u80a0\u58c1\u4e2d\u9176\u4ee3\u8c22\u73b0\u8c61\u8f83\u4e3a\u6d3b\u8dc3\uff0cFig. 5\u63d0\u4f9b\u4e86\u8003\u5bdf\u53e3\u670d\u66b4\u9732\u5f71\u54cd\u7684\u8bc4\u4f30\u6d41\u7a0b\u3002\u8be5\u56fe\u8868\u662f\u4e3a\u4e86\u7406\u89e3\u80a0\u58c1\u4ee3\u8c22\u5bfc\u81f4\u66b4\u9732\u51cf\u5c11(\u901a\u8fc7\u5229\u7528\u5df2\u7ecf\u83b7\u5f97\u809d\u810f\u4ee3\u8c22\u7684\u6570\u636e)\u7684\u6f5c\u5728\u98ce\u9669\u3002\u9ad8\u6e17\u900f\u53ef\u80fd\u4f1a\u62b5\u6d88\u90e8\u5206\u7684\u80a0\u58c1\u4ee3\u8c22\uff0c\u8be5\u73b0\u8c61\u53ef\u4ee5\u901a\u8fc7PSA\u8fdb\u884c\u5145\u5206\u7814\u7a76\u3002<\/p>\n

\u4e00\u822c\u521d\u59cb\u7684\u7814\u7a76\u4e3b\u8981\u5173\u6ce8\u9884\u6d4bCYP3A4\u7684\u80a0\u9053\u4ee3\u8c22\uff0c\u53ef\u80fd\u56e0\u4e3a\u4f7f\u7528\u8461\u8404\u67da\u6c41\u7814\u7a76\u7684\u6570\u636e\u80fd\u652f\u6301\u6a21\u578b\u7684\u9884\u6d4b\u3002GastroPlus\u8f6f\u4ef6\u53ef\u4ee5\u6574\u5408\u4ee3\u8c22\u8d21\u732e\u81f3ACAT\u6a21\u578b\u7684\u6bcf\u4e2a\u623f\u5ba4\u3002<\/p>\n

\u4f8b\u5982\u5bf9\u4e8e\u4e3b\u8981\u7ecfCYP3A4\u4ee3\u8c22\u7684\u5316\u5408\u7269\uff0c\u4f53\u5916\u809d\u5fae\u7c92\u4f53\u7684\u6e05\u9664\u6570\u636e\u53ef\u4ee5\u7528\u4e8e\u4f30\u7b97CYP3A4\u4ecb\u5bfc\u7684\u80a0\u9053\u4ee3\u8c22\u3002\u7c7b\u4f3c\u7684\u7b56\u7565\u5bf9\u4e8e\u8bc4\u4f30\u975eCYP\u80a0\u58c1\u4ee3\u8c22\u9176(\u5982UDP\u8461\u8404\u7cd6\u919b\u9178\u8f6c\u79fb\u9176\u548c\u78fa\u57fa\u8f6c\u79fb\u9176)\u4f5c\u7528\u7684\u5316\u5408\u7269\u4e5f\u662f\u975e\u5e38\u6709\u7528\u7684\u3002<\/p>\n

\u7136\u800c\u7531\u4e8e\u53d7\u5230\u80a0\u9053\u4ee3\u8c22\u9176\u4e30\u5ea6\u6570\u636e\u4ee5\u53ca\u80a0\u9053\u6392\u6cc4\u7684\u4f53\u5185\u4f30\u7b97(\u8fd8\u9700\u8981\u8fdb\u4e00\u6b65\u9a8c\u8bc1\u7684\u9014\u5f84)\u7684\u9650\u5236\uff0c\u9884\u6d4b\u975eCYP\u4ee3\u8c22\u9176\u7684\u8d21\u732e\u662f\u8f83\u4e3a\u590d\u6742\u7684\u3002<\/p>\n

Fig. 5\u4e2d\u6240\u5448\u73b0\u7684\u7b56\u7565\uff0c\u5177\u6709\u4f4e\u9003\u79bb\u80a0\u58c1\u4ee3\u8c22\u836f\u7269\u5206\u6570\u7684\u8d8b\u52bf\u3002<\/p>\n

\u56e0\u6b64\u5728\u8fdb\u884c\u9884\u6d4b\u76f8\u5173\u80a0\u58c1\u6392\u6cc4\u65f6\uff0c\u53ef\u80fd\u8fd8\u9700\u8981\u5e73\u884c\u5730\u4f7f\u7528\u4e00\u79cd\u5907\u9009\u65b9\u6848\u8bc4\u4f30\u80a0\u58c1\u4ee3\u8c22\uff0c\u4ee5\u652f\u6301\u6700\u540e\u7684\u51b3\u7b56\u3002<\/p>\n

\u8fd9\u4e9b\u8bc4\u4f30\u65b9\u6cd5\u4e5f\u4f53\u73b0\u5728Peters\u7b49\u4eba\u6587\u7ae0\u9610\u8ff0\u7684\u6a21\u578b\u5e94\u7528\u7b56\u7565\uff0c\u6587\u7ae0\u5efa\u8bae\u5c06\u52a8\u7269\u4e2d\u89c2\u6d4b\u5230\u80a0\u58c1\u4ee3\u8c22\uff0c\u8fde\u540c\u4eba\u80a0\u9053\u4ee3\u8c22\u7684\u76f8\u5173\u4f53\u5916\u6570\u636e\u548c\u5316\u5408\u7269\u7684\u751f\u7269\u836f\u5242\u5b66\u5206\u7c7b\u7b49\u56e0\u7d20\u8003\u8651\u5230\u4f4e\u9003\u79bb\u80a0\u58c1\u4ee3\u8c22\u5206\u6570\u7684\u836f\u7269\u98ce\u9669\u8bc4\u4f30\u4e2d\u3002<\/span><\/p>\n

\u6b64\u5916\uff0c\u540c\u65f6\u53d7\u80a0\u58c1\u4ee3\u8c22\u548c\u4e3b\u52a8\u8f6c\u8fd0\u7684\u5316\u5408\u7269\uff0c\u91c7\u7528\u7ecf\u9a8c\u6821\u6b63\u7684\u4ee3\u8c22\u548c\u8f6c\u8fd0IVIVE\u6bd4\u653e\u56e0\u5b50\u53ef\u80fd\u4f1a\u66f4\u52a0\u51c6\u786e\u8868\u5f81\u3002<\/span><\/p>\n

\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/p>\n

Fig. 5 PBPK<\/span>\u6a21\u578b\u8bc4\u4f30\u80a0\u58c1\u4ee3\u8c22\u7684\u7b56\u7565\uff1a<\/span><\/span>Clint-<\/span>\u809d\u810f\u56fa\u6709\u6e05\u9664\u7387\uff1b<\/span><\/span>Fg-<\/span>\u9003\u79bb\u80a0\u58c1\u4ee3\u8c22\u7684\u836f\u7269\u5206\u6570\uff1b<\/span><\/span>Km-Vmax<\/span>\u4e00\u534a\u65f6\u5e95\u7269\u7684\u6d53\u5ea6\uff1b<\/span><\/span>Vmax-<\/span>\u4ee3\u8c22\u9176\u6700\u5927\u4ee3\u8c22\u53cd\u5e94\u901f\u7387\uff1b<\/span>\u6ce8\uff1a\u80a0\u58c1\u4ee3\u8c22\u7ecf\u5e38\u4f1a\u51fa\u73b0\u9971\u548c\u73b0\u8c61\uff0c\u5982\u679c\u6709<\/span>Km<\/span>\u548c<\/span>Vmax<\/span>\u7684\u6570\u636e\u53ef\u4ee5\u8bc4\u4f30\u5242\u91cf\u4f9d\u8d56\u578b\u7684\u9971\u548c\u73b0\u8c61\u3002<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

2.5 \u4e0d\u786e\u5b9a\u6027\u548c\u53d8\u5f02\u5206\u6790<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5c3d\u7ba1\u7ecf\u5e38\u5f00\u5c55FIH\u5242\u91cf\u7684\u6a21\u62df\u9884\u6d4b\uff0c\u4f46\u8be5\u65b9\u6cd5\u53ef\u80fd\u4f1a\u5f71\u54cd\u6240\u5f97\u7684\u6570\u636e\u7ed3\u679c\uff0c\u56e0\u4e3a\u5728PBPK\u6a21\u578b\u8f93\u5165\u7684\u53c2\u6570\u5177\u6709\u4e0d\u786e\u5b9a\u6027\u4e14\u6240\u6a21\u62df\u7684\u4eba\u7fa4\u6709\u4e00\u5b9a\u7684\u53d8\u5f02\u6027\u3002\u7279\u522b\u662f\u4ece\u76d1\u7ba1\u90e8\u95e8\u7684\u89c6\u89d2\u6765\u770b\uff0c\u540c\u65f6\u8003\u8651\u5230\u4e0d\u786e\u5b9a\u6027\u548c\u53d8\u5f02\u6027\u662f\u975e\u5e38\u91cd\u8981\u7684\u3002\u5f53\u91c7\u7528PBPK\u6a21\u578b\u9884\u6d4bFIH\u5242\u91cf\u65f6\uff0c\u63a2\u5bfb\u6a21\u578b\u53c2\u6570\u7684\u4e0d\u786e\u5b9a\u662f\u975e\u5e38\u5173\u952e\u7684\uff1a\u56e0\u4e3a\u5728\u8fd9\u4e2a\u9636\u6bb5\u6709\u5f88\u591a\u672a\u77e5\u7684\u56e0\u7d20\uff0cCompound 3 (\u89c1\u5e94\u7528\u6848\u4f8b\u76844.3\u7ae0\u8282)\u4e13\u95e8\u4e3e\u4f8b\u8bf4\u660e\u4e86\u8be5\u60c5\u51b5\u3002<\/p>\n

PSA\u5206\u6790\u53ef\u7528\u4e8e\u786e\u5b9a\u4e3b\u8981\u7684\u4e0d\u786e\u5b9a\u56e0\u7d20\uff0c\u65e0\u8bba\u662f\u56e0\u4e3a\u6570\u636e\u7684\u9650\u5236\uff0c\u673a\u5236\u7406\u89e3\u7684\u7f3a\u5c11\uff0c\u4e0d\u80fd\u9884\u6d4b\u4ee3\u8c22\u9971\u548c\u6216\u5438\u6536\u673a\u5236\uff0c\u6216\u8005\u662f\u4f53\u5916\u548c\u4f53\u5185\u6570\u636e\u7684\u5dee\u5f02\u3002EMA\u9f13\u52b1\u91c7\u7528PSA\u4ee5\u8868\u5f81PBPK\u6a21\u578b\u53c2\u6570\u4e0d\u786e\u5b9a\u6027\u7684\u7a0b\u5ea6\u3002<\/p>\n

\u4e0d\u786e\u5b9a\u6027\u53ef\u4ee5\u8f6c\u79fb\u5230\u6c47\u603b\u7684PBPK\u6a21\u578b\u7ed3\u679c\u4e2d\uff0c\u5e76\u5bfc\u81f4\u4e34\u5e8aPK\u9884\u671f\u7ed3\u679c\u7684\u9650\u5236\u3002\u6709\u65f6\uff0c\u5173\u6ce8\u5355\u4e2a\u5173\u952e\u6a21\u578b\u53c2\u6570\u4e5f\u662f\u975e\u5e38\u6709\u4ef7\u503c\u7684\u3002\u4f8b\u5982\uff0c\u6e05\u9664\u7387\u7ecf\u5e38\u662f\u4e00\u4e2a\u654f\u611f\u53c2\u6570\u4e14\u6ca1\u6709\u975e\u5e38\u53ef\u9760\u7684\u4fe1\u5fc3\uff0c\u56e0\u4e3a\u6765\u81ea\u5fae\u7c92\u4f53\u548c\u809d\u7ec6\u80de\u6240\u9884\u6d4b\u6e05\u9664\u7387\u7684\u4e0d\u4e00\u81f4\uff0c\u6216\u8005\u4e34\u5e8a\u524d\u79cd\u5c5e\u4f53\u5916\u548c\u4f53\u5185\u6e05\u9664\u7387\u7684\u5dee\u5f02\u3002\u4e00\u79cd\u65b9\u5f0f\u662f\u5bf9\u4e8e\u4e0d\u786e\u5b9a\u7684\u6a21\u578b\u53c2\u6570\u7ed9\u51fa\u4e00\u4e2a\u9884\u6d4b\u8303\u56f4\uff0c\u6216\u8005\u662f\u9884\u6d4b\u4e00\u4e2a\u6700\u6709\u53ef\u80fd\u7684\u4f30\u7b97\u503c\u548c\u6700\u5dee\u60c5\u51b5\u7684\u7ed3\u679c\u3002\u6e05\u6670\u5730\u8868\u8ff0\u9884\u6d4b\u8303\u56f4\u6240\u4ee3\u8868\u7684\u5185\u5bb9\u6bd4\u8f83\u91cd\u8981\uff0c\u4ee5\u4fbf\u53ef\u4ee5\u5408\u9002\u5730\u5904\u7406\u76f8\u5173\u4fe1\u606f\u3002<\/p>\n

\u6709\u65f6\uff0c\u591a\u4e2a\u53c2\u6570\u7684\u4e0d\u786e\u5b9a\u6027\u4f20\u8f93\u4e5f\u5f88\u91cd\u8981\uff0c\u6bd4\u5982\u5f53\u6e05\u9664\u7387\u548c\u5438\u6536\u7684\u9884\u6d4b\u90fd\u5b58\u5728\u4e0d\u786e\u5b9a\u65f6\u3002\u8fd9\u79cd\u60c5\u51b5\u4e0b\uff0c\u4e09\u7ef4\u7684PSA (\u4e09\u7ef4\u7ed3\u679c\u5c55\u793a\u9884\u6d4b\u7684PK\u53c2\u6570)\u6240\u5448\u73b0\u7684\u6a21\u62df\u7ed3\u679c\u5bf9\u4e8e\u786e\u5b9a\u53ef\u80fd\u7684\u4e0d\u786e\u5b9a\u56e0\u7d20\u662f\u975e\u5e38\u6709\u7528\u7684\u53c2\u8003\u3002<\/p>\n

\u5bf9\u4e8e\u9884\u6d4b\u7684\u53d8\u5f02\u6027\uff0cGastroPlus\u7684\u7fa4\u4f53\u6a21\u62df\u529f\u80fd\u53ef\u4ee5\u7528\u4e8e\u6a21\u62df\u591a\u4e2a\u6a21\u578b\u53c2\u6570(\u5e38\u662f\u751f\u7406\u5b66)\u5728\u6240\u5b9a\u4e49\u7684\u53d8\u5f02\u5206\u5e03\u8303\u56f4\u5185\u53d8\u5316\u65f6\u7684\u4e34\u5e8a\u8868\u73b0\u3002\u8fd9\u4e00\u5f3a\u5927\u7684\u6280\u672f\u5df2\u7ecf\u5728\u786e\u5b9a\u7279\u5b9aP450\u57fa\u56e0\u4e9a\u578b\/\u57fa\u56e0\u591a\u6001\u6027\u7684\u5f71\u54cd\uff0c\u7406\u89e3\u9884\u671f\u836f\u7269\u836f\u7269\u76f8\u4e92\u4f5c\u7528\u7684\u8303\u56f4\u548c\u6a21\u62df\u75be\u75c5\u5bf9\u75c5\u4ebaPK\u5f71\u54cd\u7b49\u65b9\u9762\u5f97\u5230\u4e86\u5e94\u7528\u3002\u5f53\u7136\uff0c\u4e00\u4e9b\u7b80\u5355\u7684\u9014\u5f84(\u5982\u5bf9\u6bd4\u4e00\u4e2a\u5178\u578b\u7684\u75c5\u4eba\u5728\u7a7a\u8179\u548c\u9971\u8179\u72b6\u6001\u4e0b\u6240\u9884\u6d4bPK\u7684\u53d8\u5316\uff0c\u6216\u8005\u5bf9\u6bd4\u4e00\u4e2a\u5065\u5eb7\u4eba\u548c\u75c5\u4ebaPK\u9884\u6d4b\u7684\u5dee\u5f02\u7b49)\u5bf9\u7406\u89e3\u53d8\u5f02\u6027\u4e5f\u662f\u975e\u5e38\u6709\u7528\u7684\u3002\u53d8\u5f02\u6027\u7684\u9884\u6d4b\u5728\u4eba\u4f53\u6570\u636e\u83b7\u5f97\u540e\u53ef\u80fd\u4f1a\u66f4\u52a0\u6709\u7528\uff0c\u8fd9\u4e5f\u53ef\u4ee5\u6539\u5584\u201c\u81ea\u9876\u5411\u4e0b\u201d\u7684PBPK\u6a21\u578b\u9884\u6d4b\u80fd\u529b\u3002<\/p>\n

\u5982Compound 1 (\u89c1\u5e94\u7528\u6848\u4f8b\u76844.1\u7ae0\u8282)\uff0c\u66f4\u52a0\u5168\u9762\u5730\u8bc4\u4f30\u4e0d\u786e\u5b9a\u6027\u548c\u6f5c\u5728\u7684\u53d8\u5f02\u53ef\u4ee5\u5e2e\u52a9\u907f\u514d\u9700\u8981\u589e\u52a0\u989d\u5916\u6837\u54c1\u91c7\u96c6\u70b9\u7684\u4e34\u5e8a\u65b9\u6848\u4fee\u8ba2\u3002\u56fe6\u63d0\u4f9b\u4e86\u4e00\u4e2aPBPK\u6a21\u578b\u7684\u8f93\u5165\u53c2\u6570\u6e05\u5355\uff0c\u540c\u65f6\u4e5f\u5e94\u7528\u4e8e\u8003\u8651\u4e0d\u786e\u5b9a\u7684\u8bc4\u4f30\u3002\u4ec5\u6765\u81eaFig. 6\u7684\u4e00\u7cfb\u5217\u53c2\u6570(\u7531\u5316\u5408\u7269\u6027\u8d28\u51b3\u5b9a\u7684)\u5bf9\u4e8e\u4e00\u4e2a\u7279\u5b9a\u7684PBPK\u6a21\u578b\u662f\u975e\u5e38\u91cd\u8981\u7684\u3002<\/p>\n

\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/p>\n

Fig. 6 <\/span>\u901a\u8fc7\u5206\u5b50\u6027\u8d28\u548c\u4e0d\u786e\u5b9a\u8bc4\u4f30\u9a71\u52a8\u7684<\/span>PSA<\/span>\u5206\u6790\u6307\u5bfc<\/span>PBPK<\/span>\u5efa\u6a21\u7b56\u7565\uff1a<\/span><\/span>3D-<\/span>\u4e09\u7ef4\uff1b<\/span><\/span>ADME-<\/span>\u5438\u6536\uff0c\u5206\u5e03\uff0c\u4ee3\u8c22\u548c\u6392\u6cc4\uff1b<\/span><\/span>APL-<\/span>\u9178\u6027\u78f7\u916f\uff1b<\/span><\/span>ASF-<\/span>\u5438\u6536\u653e\u5927\u56e0\u5b50\uff1b<\/span><\/span>BCS-<\/span>\u751f\u7269\u836f\u5242\u5b66\u5206\u7c7b\uff1b<\/span><\/span>BPR-<\/span>\u5168\u8840\u8840\u6d46\u6d53\u5ea6\u6bd4\uff1b<\/span><\/span>BSSR-<\/span>\u80c6\u9178\u76d0\u589e\u6eb6\u56e0\u5b50\uff1b<\/span><\/span>Capt-<\/span>\u9178\u6027\u78f7\u916f\u5728\u7ec4\u7ec7\u4e2d\u7684\u6d53\u5ea6\uff1b<\/span><\/span>Clint-<\/span>\u809d\u810f\u56fa\u6709\u6e05\u9664\u7387\uff1b<\/span><\/span>FIH-<\/span>\u9996\u6b21\u4eba\u4f53\uff1b<\/span><\/span>fup-<\/span>\u8840\u6d46\u6e38\u79bb\u836f\u7269\u5206\u6570\uff1b<\/span><\/span>Km-Vmax<\/span>\u4e00\u534a\u65f6\u5e95\u7269\u7684\u6d53\u5ea6\uff1b<\/span><\/span>MPT-<\/span>\u5e73\u5747\u6c89\u6dc0\u65f6\u95f4\uff1b<\/span><\/span>PSA-<\/span>\u53c2\u6570\u654f\u611f\u6027\u5206\u6790\uff1b<\/span><\/span>Peff-<\/span>\u6709\u6548\u6e17\u900f\u6027\uff1b<\/span><\/span>SI-<\/span>\u5c0f\u80a0\uff1b<\/span><\/span>SolFactor-<\/span>\u6eb6\u89e3\u56e0\u5b50\uff1b<\/span><\/span>Vmax-<\/span>\u4ee3\u8c22\u9176\u6700\u5927\u4ee3\u8c22\u53cd\u5e94\u901f\u7387<\/span><\/span><\/strong><\/p>\n

\u53e6\u5916\uff0c\u539f\u6587\u4f5c\u8005\u5217\u4e3e\u4e86\u53ef\u4ee5\u6539\u5584PBPK\u5efa\u6a21\u9884\u6d4bFIH\u7ed3\u679c\u7684\u4e00\u4e9b\u673a\u4f1a\u533a\u57df(Table 1)\uff0c\u8fd9\u4e9b\u4e5f\u5e94\u5f53\u4e00\u5e76\u8003\u8651\u5230\u4e0d\u786e\u5b9a\u8bc4\u4f30\u5185\u5bb9\u4e2d\u3002
<\/p>\n

Table 1 \u57fa\u4e8e<\/span>PBPK\u5efa\u6a21\u65b9\u6cd5\u7684\u673a\u4f1a\u533a\u57df<\/span><\/strong><\/span><\/p>\n

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

\u4ee3\u8c22\u548c\u6e05\u9664<\/span><\/p>\n<\/td>\n

\n

\u5f53\u628a\u8f6c\u8fd0\u4f53\u7684\u4f5c\u7528<\/span>(<\/span>\u5982\u80c6\u6c41\u6392\u6cc4\u6216\u6444\u53d6\u9650\u5236\u7684\u809d\u810f\u6e05\u9664<\/span>)<\/span>\u8003\u8651\u8fdb\u6765\u540e\u6a21\u578b\u7684\u9884\u6d4b\u80fd\u529b\uff1b<\/span><\/p>\n

\u809d\u5916\u4ee3\u8c22\u5bf9\u6e05\u9664\u7387\u7684\u9884\u6d4b\u80fd\u529b\uff1b<\/span><\/p>\n

\u4e0d\u540c\u79cd\u5c5e\u95f4\u809d\u80a0\u5faa\u73af\u7684\u8f6c\u5316\u3002<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

\u5206\u5e03<\/span><\/p>\n<\/td>\n

\n

\u5f53\u8840\u6d46\u86cb\u767d\u7ed3\u5408\u7387\u5f88\u9ad8\u800c\u65e0\u6cd5\u51c6\u786e\u6d4b\u5b9a\u65f6\uff0c\u53ef\u91c7\u7528\u6539\u5584\u7684\u65b9\u6cd5\u9884\u6d4b<\/span>Vss;<\/span><\/p>\n

\u5f53\u8f6c\u8fd0\u4f53\u8d77\u5230\u4e00\u5b9a\u4f5c\u7528\u65f6\u53ef\u91c7\u7528\u5305\u62ec\u9884\u6d4b\u7684\u7ec4\u7ec7\u4e2d\u836f\u7269\u6d53\u5ea6\u8fdb\u884c\u9a8c\u8bc1\u3002<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

\u53e3\u670d\u5438\u6536<\/span><\/p>\n<\/td>\n

\n

\u91c7\u7528\u9664\u4e86<\/span>CYP3A4  (<\/span>\u5982<\/span>UGT1A1<\/span>\u6216<\/span>UGT2B7)<\/span>\u7684\u6570\u636e\u9884\u6d4b\u548c\u9a8c\u8bc1\u80a0\u9053\u4ee3\u8c22\u3002<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

CYP-<\/span>\u7ec6\u80de\u8272\u7d20<\/span>P450<\/span>\uff1b<\/span>UGT-UDP<\/span>\u8461\u8404\u7cd6\u919b\u9178\u8f6c\u79fb\u9176\uff1b<\/span>Vss-<\/span>\u7a33\u6001\u5206\u5e03\u4f53\u79ef<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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


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

<\/section>\n<\/section>\n
<\/section>\n<\/section>\n
\n
\n
\n
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3. \u6750\u6599\u4e0e\u65b9\u6cd5<\/p>\n

4. \u5e94\u7528\u6848\u4f8b
<\/p>\n

5. \u8ba8\u8bba\u4e0e\u7ed3\u8bed<\/p>\n

\u8bf7\u89c1\u540c\u5929\u53d1\u5e03\u7684\u300a\uff08\u4e0b\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565-\u5e94\u7528\u6848\u4f8b\u300b<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n


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

\n
\n
\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/p>\n
\n

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

\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/section>\n

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

Neil A. Miller, Micaela B. Reddy, Aki T. Heikkinen, et al., Physiologically Based Pharmacokinetic Modelling for First-In-Human Predictions: An UpdatedModel Building Strategy Illustrated with Challenging Industry Case Studies. Clin Pharmacokinet. 2019 Feb 7.   <\/p>\n

IF: 4.464<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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

\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\u672c\u6587\u5185\u5bb9\u7531\u6280\u672f\u56e2\u961f\u539f\u521b\u89e3\u8bfb\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
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<\/section>\n
<\/section>\n
<\/section>\n<\/section>\n<\/section>\n
\n

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

\n
\n
\n

\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
\n


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

\n
\n
\"\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b\u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565\"<\/section>\n<\/section>\n<\/section>\n<\/section>\n


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

\uff08\u4e0a\uff09\u57fa\u4e8e\u751f\u7406\u836f\u4ee3\u52a8\u529b\u5b66\u6a21\u578b \u9884\u6d4b\u9996\u6b21\u4eba\u4f53PK\u7684\u65b0\u7b56\u7565 \u5bfc\u8bfb \u5404\u5927\u5236\u836f\u4f01\u4e1a\u90fd\u5728\u5e7f\u6cdb\u5730\u4f7f\u7528PBPK\u6a21\u578b\uff0c\u539f\u6587\u4f5c\u8005 […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[2],"tags":[],"_links":{"self":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/86601"}],"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=86601"}],"version-history":[{"count":1,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/86601\/revisions"}],"predecessor-version":[{"id":86624,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/86601\/revisions\/86624"}],"wp:attachment":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media?parent=86601"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/categories?post=86601"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/tags?post=86601"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}