{"id":2297,"date":"2026-11-10T09:55:53","date_gmt":"2026-11-10T01:55:53","guid":{"rendered":"https:\/\/www.millibuff.com\/?p=2297"},"modified":"2026-11-10T09:57:33","modified_gmt":"2026-11-10T01:57:33","slug":"%e5%b0%8f%e7%89%9b%e6%b4%9e%e5%af%9f-%e9%a6%96%e6%ac%a1%e4%ba%ba%e4%bd%93%e8%af%95%e9%aa%8c%e7%9a%84%e8%b5%b7%e5%a7%8b%e5%89%82%e9%87%8f%ef%bc%8c%e7%a9%b6%e7%ab%9f%e6%98%af%e6%80%8e%e4%b9%88","status":"publish","type":"post","link":"https:\/\/www.millibuff.com\/?p=2297","title":{"rendered":"\u5c0f\u725b\u6d1e\u5bdf | \u9996\u6b21\u4eba\u4f53\u8bd5\u9a8c\u7684\u8d77\u59cb\u5242\u91cf\uff0c\u7a76\u7adf\u662f\u600e\u4e48\u7b97\u51fa\u6765\u7684\uff1f"},"content":{"rendered":"\n<h5 class=\"wp-block-heading\"><strong>\u4e00\u3001FIH\u5242\u91cf<\/strong><\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">\u8d77\u59cb\u5242\u91cf\u7684\u9009\u62e9\u672c\u8d28\u4e0a\u662f\u4e00\u4e2a\u201c\u7a97\u53e3\u95ee\u9898\u201d\uff1a\u5fc5\u987b\u4f4e\u5230\u8db3\u4ee5\u4fdd\u8bc1\u53d7\u8bd5\u8005\u5b89\u5168\uff0c\u53c8\u5fc5\u987b\u9ad8\u5230\u907f\u514d\u8fc7\u5ea6\u5197\u957f\u7684\u5242\u91cf\u9012\u589e\u2014\u2014\u6bcf\u4e00\u6b21\u9012\u589e\u90fd\u610f\u5473\u7740\u66f4\u591a\u7684\u5242\u91cf\u961f\u5217\u3001\u66f4\u957f\u7684\u5468\u671f\u3001\u66f4\u9ad8\u7684\u6210\u672c\u3002\u51c6\u786e\u7684\u4e34\u5e8a\u524d\u4eba\u4f53PK\u9884\u6d4b\uff0c\u5e73\u5747\u53ef\u4e3a\u5242\u91cf\u722c\u5761\u9636\u6bb5\u8282\u77011\uff5e6\u4e2a\u6708\u7684\u5f00\u53d1\u65f6\u95f4\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u6ca1\u6709\u54ea\u4e00\u79cd\u65b9\u6cd5\u88ab\u516c\u8ba4\u6700\u51c6\uff0c\u76ee\u524d\u7684\u4e3b\u6d41\u505a\u6cd5\u662f\u201c\u591a\u6cd5\u5e76\u7b97\u3001\u4ea4\u53c9\u9a8c\u8bc1\u201d\u3002\u5f52\u7eb3\u4e3a\u4e94\u5927\u6d41\u6d3e\uff1a<\/p>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><tbody><tr><td><strong>\u65b9\u6cd5<\/strong><\/td><td><strong>\u6838\u5fc3\u601d\u8def<\/strong><\/td><td><strong>\u4f18\u52bf<\/strong><\/td><td><strong>\u5c40\u9650<\/strong><\/td><\/tr><tr><td><strong>NOAEL\u6cd5<\/strong><\/td><td>\u52a8\u7269NOAEL\u6309\u4f53\u8868\u9762\u79ef\u6362\u7b97\u4eba\u4f53\u7b49\u6548\u5242\u91cf\uff08HED\uff09\uff0c\u9664\u4ee5\u5b89\u5168\u56e0\u5b50\u5f97MRSD<\/td><td>\u5c0f\u5206\u5b50\u836f\u7269\u5b89\u5168\u6027\u8bb0\u5f55\u826f\u597d\uff0c\u7b80\u5355\u5b9e\u7528<\/td><td>\u5b89\u5168\u56e0\u5b50\u504f\u7ecf\u9a8c\u3001\u6574\u4f53\u4fdd\u5b88\uff1b\u5ffd\u89c6\u836f\u7406\u5b66\u6d3b\u6027\u5242\u91cf\u4e0e\u79cd\u5c5e\u95f4\u836f\u6548\u5b66\u5dee\u5f02<\/td><\/tr><tr><td><strong>MABEL\u6cd5<\/strong><\/td><td>\u4ee5\u4ea7\u751f\u4efb\u4f55\u751f\u7269\u5b66\u6548\u5e94\uff08\u6bd2\u6027\u6216\u9884\u671f\u836f\u7406\u4f5c\u7528\uff09\u7684\u6700\u4f4e\u5242\u91cf\u4e3a\u8d77\u70b9<\/td><td>\u57fa\u4e8e\u836f\u7406\u5b66\u77e5\u8bc6\u800c\u975e\u7ecf\u9a8c\u56e0\u5b50\uff0c\u9002\u7528\u4e8e\u751f\u7269\u836f\u4e0e\u6fc0\u52a8\u5242<\/td><td>\u9700\u8981\u5927\u91cf\u673a\u5236\u6570\u636e\uff08\u9776\u70b9\u7ed3\u5408\u3001\u53d7\u4f53\u5360\u7528\u3001\u66b4\u9732-\u54cd\u5e94\uff09<\/td><\/tr><tr><td><strong>\u7c7b\u4f3c\u836f\u7269\u6bd4\u8f83\u6cd5<\/strong><\/td><td>\u501f\u7528\u7ed3\u6784\u7c7b\u4f3c\u3001\u5df2\u6709\u4e34\u5e8a\u6570\u636e\u836f\u7269\u7684\u5242\u91cf\u6309NOAEL\u6bd4\u503c\u6298\u7b97<\/td><td>\u7b80\u5355\uff0c\u6240\u9700\u6570\u636e\u6781\u5c11<\/td><td>\u4ec5\u9002\u7528\u4e8e\u6781\u5c11\u6570\u6709\u201c\u5b6a\u751f\u201d\u836f\u7269\u7684\u5019\u9009\u5206\u5b50<\/td><\/tr><tr><td><strong>PK\u5bfc\u5411\u6cd5<\/strong><\/td><td>\u9884\u6d4b\u4eba\u4f53\u6e05\u9664\u7387\u4e0e\u751f\u7269\u5229\u7528\u5ea6\uff0c\u53cd\u63a8\u8fbe\u5230\u76ee\u6807\u66b4\u9732\u6240\u9700\u7684\u5242\u91cf<\/td><td>\u57fa\u4e8e\u836f\u4ee3\u52a8\u529b\u5b66\u6027\u8d28\u800c\u975e\u7ecf\u9a8c\u56e0\u5b50\uff0c\u673a\u5236\u6027\u66f4\u5f3a<\/td><td>\u5ffd\u89c6\u79cd\u5c5e\u95f4\u836f\u6548\u5b66\u5dee\u5f02\uff1b\u4f9d\u8d56\u4eba\u4f53PK\u9884\u6d4b\u7684\u51c6\u786e\u6027<\/td><\/tr><tr><td><strong>PK\/PD\u5efa\u6a21\u6cd5<\/strong><\/td><td>\u6574\u5408\u66b4\u9732-\u54cd\u5e94\u5173\u7cfb\u7684\u6570\u5b66\u6a21\u578b\uff0c\u6a21\u62df\u4eba\u4f53\u5242\u91cf-\u66b4\u9732-\u54cd\u5e94-\u65f6\u95f4\u5168\u8fc7\u7a0b<\/td><td>\u540c\u65f6\u8003\u8651PK\u4e0ePD\u7684\u79cd\u5c5e\u5dee\u5f02\uff0c\u51cf\u5c11\u5bf9\u7ecf\u9a8c\u5b89\u5168\u56e0\u5b50\u7684\u4f9d\u8d56<\/td><td>\u5efa\u6a21\u4e0e\u9a8c\u8bc1\u5de5\u4f5c\u91cf\u5927<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">\u8868&nbsp; \u4e94\u79cdFIH\u5242\u91cf\u4f30\u7b97\u65b9\u6cd5\u5bf9\u6bd4<\/p>\n\n\n\n<h6 class=\"wp-block-heading\"><strong>1. NOAEL\u6cd5<\/strong><\/h6>\n\n\n\n<p class=\"wp-block-paragraph\">2005\u5e747\u6708\uff0cFDA\u53d1\u5e03\u884c\u4e1a\u6307\u5357\u300aEstimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers\u300b\uff0c\u786e\u7acb\u4e86\u5982\u4e0b\u6d41\u7a0b\uff1a\u2460\u786e\u5b9a\u5404\u52a8\u7269\u79cd\u5c5e\u7684NOAEL \u2192 \u2461\u6309\u4f53\u8868\u9762\u79ef\u6362\u7b97\u4e3aHED \u2192 \u2462\u9009\u62e9\u6700\u654f\u611f\u79cd\u5c5e\u7684\u6700\u4f4eHED \u2192 \u2463\u9664\u4ee5\u5b89\u5168\u56e0\u5b50\uff08\u4e00\u822c\u4e0d\u4f4e\u4e8e10\uff09\u5f97\u5230\u4eba\u4f53\u6700\u5927\u63a8\u8350\u8d77\u59cb\u5242\u91cf\uff08MRSD\uff09\u2192\u2464\u5fc5\u8981\u65f6\u8fd8\u9700\u6839\u636e\u836f\u7406\u5b66\u6d3b\u6027\u5242\u91cf\uff08PAD\uff09\u5411\u4e0b\u8c03\u6574\u3002<\/p>\n\n\n\n<figure class=\"wp-block-image aligncenter size-full is-resized\"><img fetchpriority=\"high\" decoding=\"async\" width=\"508\" height=\"551\" src=\"https:\/\/www.millibuff.com\/wp-content\/uploads\/2026\/11\/image-8.png\" alt=\"\" class=\"wp-image-2299\" style=\"width:713px;height:auto\" srcset=\"https:\/\/www.millibuff.com\/wp-content\/uploads\/2026\/11\/image-8.png 508w, https:\/\/www.millibuff.com\/wp-content\/uploads\/2026\/11\/image-8-277x300.png 277w\" sizes=\"(max-width: 508px) 100vw, 508px\" \/><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">\u56fe1\uff1a\u4ee5\u6bd2\u7406\u8bd5\u9a8c\u5242\u91cf\u4e3a\u57fa\u7840\u4f30\u7b97 MRSD \u7684\u6d41\u7a0b<sup>[2]<\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u4e00\u4e2a\u7b80\u5355\u7684\u8ba1\u7b97\u793a\u4f8b\uff1a<\/strong><\/p>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><tbody><tr><td><strong>\u6b65\u9aa4<\/strong><\/td><td><strong>\u5185\u5bb9<\/strong><\/td><td><strong>\u7ed3\u679c<\/strong><\/td><\/tr><tr><td>Step 1<\/td><td>\u5927\u9f20 NOAEL 50 mg\/kg\uff1b\u72ac NOAEL 15 mg\/kg<\/td><td>\u2014<\/td><\/tr><tr><td>Step 2<\/td><td>\u4f7f\u7528\u4f53\u8868\u9762\u79ef\u6cd5\u5c06NOAEL\u6362\u7b97\u81f3HED\uff1a\u5927\u9f20HED = 50\u00f7(36.88\/6.04)\u22488.2&nbsp;mg\/kg\uff1b\u72ac HED = 15\u00f7(36.88\/21.47)\u22488.7&nbsp;mg\/kg<\/td><td>\u2014<\/td><\/tr><tr><td>Step 3<\/td><td>\u5927\u9f20\u6362\u7b97\u5f97\u5230\u7684 HED \u66f4\u4f4e\uff0c\u9ed8\u8ba4\u9009\u62e9\u5927\u9f20\u6765\u6e90\u6570\u636e<\/td><td>HED=8.2&nbsp;mg\/kg<\/td><\/tr><tr><td>Step 4<\/td><td>\u65e0\u7279\u6b8a\u98ce\u9669\u4fe1\u53f7\uff0c\u5b89\u5168\u7cfb\u6570 SF \u53d6\u9ed8\u8ba4\u503c 10<\/td><td>MRSD=8.2\u00f710=0.82&nbsp;mg\/kg<\/td><\/tr><tr><td>Step 5<\/td><td>\u5047\u8bbe\u836f\u7406\u5b66 HED \u4e3a 5 mg\/kg\uff0c\u5927\u4e8e 0.82 mg\/kg\uff0c\u65e0\u9700\u8fdb\u4e00\u6b65\u4e0b\u8c03\u5242\u91cf<\/td><td>\u6700\u7ec8MRSD\u22480.82&nbsp;mg\/kg<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">\u4e00\u4e2a\u5e38\u88ab\u5ffd\u89c6\u7684\u7ec6\u8282\uff1a\u6362\u7b97\u57fa\u51c6\u7684\u9009\u62e9\u4f1a\u5267\u70c8\u5f71\u54cd\u7ed3\u679c\u3002\u82e5\u5c0f\u9f20\u3001\u5927\u9f20\u3001\u72ac\u6539\u6309\u4f53\u91cd\u800c\u975e\u4f53\u8868\u9762\u79ef\u6362\u7b97\uff0cHED\u5c06\u5206\u522b\u88ab\u653e\u592712\u500d\u30016\u500d\u548c2\u500d\u3002\u6307\u5357\u4e4b\u6240\u4ee5\u9009\u62e9\u4f53\u8868\u9762\u79ef\uff0c\u6b63\u662f\u4e3a\u4e86\u4fdd\u5b88\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u4f46TGN1412\u4e8b\u4ef6\u66b4\u9732\u4e86NOAEL\u6cd5\u7684\u6839\u672c\u76f2\u533a\u2014\u2014\u5b83\u56de\u7b54\u7684\u662f<\/strong><strong>\u201c<\/strong><strong>\u52a8\u7269\u6ca1\u51fa\u4e8b\u7684\u5242\u91cf<\/strong><strong>\u201d<\/strong><strong>\uff0c\u800c\u4e0d\u662f<\/strong><strong>\u201c<\/strong><strong>\u4eba\u4f53\u5f00\u59cb\u8d77\u6548\u7684\u5242\u91cf<\/strong><strong>\u201d<\/strong>\u3002\u5f53\u836f\u7269\u7684\u836f\u6548\u5b66\u654f\u611f\u6027\u5b58\u5728\u5de8\u5927\u79cd\u5c5e\u5dee\u5f02\uff08\u6bd4\u5982TGN1412\u9776\u5411\u7684CD28\u901a\u8def\uff0c\u4eba\u7c7bT\u7ec6\u80de\u7684\u5e94\u7b54\u8fdc\u6bd4\u7334\u654f\u611f\uff09\u65f6\uff0c\u518d\u5927\u7684\u5b89\u5168\u7cfb\u6570\u4e5f\u53ef\u80fd\u5931\u7075\u3002<\/p>\n\n\n\n<h6 class=\"wp-block-heading\"><strong>2. MABEL<\/strong><strong>\u6cd5<\/strong><\/h6>\n\n\n\n<p class=\"wp-block-paragraph\">TGN1412\u4e8b\u4ef6\u540e\uff0c\u6b27\u6d32\u836f\u54c1\u7ba1\u7406\u5c40\uff08\u539fEMEA\uff0c\u73b0EMA\uff09\u4e8e2007\u5e74\u53d1\u5e03FIH\u8bd5\u9a8c\u98ce\u9669\u7ba1\u7406\u6307\u5357\uff0c\u5f15\u5165MABEL\uff08\u6700\u4f4e\u9884\u671f\u751f\u7269\u6548\u5e94\u6c34\u5e73\uff09\u6982\u5ff5\uff1a\u4ee5\u5f15\u8d77\u4efb\u4f55\u751f\u7269\u5b66\u6548\u5e94\u2014\u2014\u65e0\u8bba\u6bd2\u6027\u8fd8\u662f\u9884\u671f\u836f\u7406\u4f5c\u7528\u2014\u2014\u7684\u6700\u4f4e\u5242\u91cf\u4f5c\u4e3a\u8d77\u70b9\u3002\u5176\u8ba1\u7b97\u4f9d\u6258\u56db\u7c7bPK\/PD\u6570\u636e\uff1a\u2460\u9776\u70b9\u5728\u4eba\u4e0e\u52a8\u7269\u7ec6\u80de\u4e0a\u7684\u7ed3\u5408\u4e0e\u53d7\u4f53\u5360\u7528\uff1b\u2461\u4f53\u5916\u6d53\u5ea6-\u6548\u5e94\u66f2\u7ebf\uff1b\u2462\u52a8\u7269\u4f53\u5185\u5242\u91cf-\u66b4\u9732-\u6548\u5e94\uff1b\u2463\u52a8\u7269\u836f\u7406\u6d3b\u6027\u5242\u91cf\u4e0b\u7684\u66b4\u9732\u6c34\u5e73\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u5bf9\u4e8eTGN1412\uff0c\u91c7\u7528\u57fa\u4e8eMABEL\u7684\u65b9\u6cd5\u4f30\u7b97\u7684FIH\u5242\u91cf\u4e3a0.001 mg\/kg\uff0831\uff09\u3002\u76f8\u6bd4\u4e4b\u4e0b\uff0c\u91c7\u7528\u57fa\u4e8e NOAEL \u7684\u65b9\u6cd5\u4f30\u7b97\u7684TGN1412\u7684FIH\u5242\u91cf\u4e3a0.1 mg\/kg\uff0c\u8fd9\u5c06\u5bfc\u81f4\u53d7\u4f53\u5360\u636e\u7387\u8d85\u8fc790%\uff0c\u6781\u53ef\u80fd\u5bfc\u81f4\u4e0d\u826f\u53cd\u5e94\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u5bf9\u4e8e\u4f5c\u7528\u4e8e\u5173\u952e\u751f\u7406\u7cfb\u7edf\u7684\u6fc0\u52a8\u578b\u751f\u7269\u836f\uff0c\u6307\u5357\u5efa\u8bae\u9996\u6b21\u7ed9\u836f\u7684\u53d7\u4f53\u5360\u7528\u4e0d\u8d85\u8fc710%\u3002EMA\u5f3a\u70c8\u63a8\u8350\u540c\u65f6\u8ba1\u7b97NOAEL\u6cd5\u4e0eMABEL\u6cd5\u7ed3\u679c\uff0c\u79d1\u5b66\u8bba\u8bc1\u540e\u9009\u62e9\u66f4\u4f4e\u5b89\u5168\u8d77\u59cb\u5242\u91cf\u3002MABEL\u6cd5\u5728\u540e\u7eed\u7684\u751f\u7269\u836f\u5f00\u53d1\u4e2d\u5df2\u6210\u4e3a\u6807\u51c6\u64cd\u4f5c\u3002<\/p>\n\n\n\n<h6 class=\"wp-block-heading\"><strong>3<\/strong><strong>. PK\u5bfc\u5411\u6cd5<\/strong><\/h6>\n\n\n\n<p class=\"wp-block-paragraph\">Dose = (CL<sub>human<\/sub> \u00d7 AUC<sub>animal<\/sub>) \/ F<sub>human<\/sub><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u8d77\u59cb\u53e3\u670d\u5242\u91cf = \u9884\u6d4b\u4eba\u4f53\u6e05\u9664\u7387 \u00d7 \u6307\u793a\u52a8\u7269NOAEL\u66b4\u9732\u91cf\uff08AUC\uff09\u00f7 \u9884\u6d4b\u4eba\u4f53\u53e3\u670d\u751f\u7269\u5229\u7528\u5ea6\uff1b\u4ea6\u53ef\u7528 C<sub>ss<\/sub> \u6216 C<sub>max<\/sub> \u66ff\u4ee3AUC\u4f5c\u4e3a\u76ee\u6807\u66b4\u9732\u6307\u6807<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u5177\u4f53\u64cd\u4f5c\u4e2d\uff0c\u5148\u5728\u591a\u4e2a\u52a8\u7269\u79cd\u5c5e\u4e2d\u786e\u5b9aNOAEL\u53ca\u5bf9\u5e94AUC\uff0c\u9009\u62e9NOAEL\u6700\u4f4e\u7684\u79cd\u5c5e\u4f5c\u4e3a\u201c\u6307\u793a\u52a8\u7269\u201d\uff1bMahmood\u7b49\u4eba\u5219\u5efa\u8bae\u9009\u62e9\u6e05\u9664\u7387\uff08\u6309\u5343\u514b\u4f53\u91cd\uff09\u4e0e\u9884\u6d4b\u4eba\u4f53\u503c\u6700\u63a5\u8fd1\u7684\u79cd\u5c5e\uff0c\u518d\u4ee5\u52a8\u7269CL\u4e0e\u4eba\u4f53\u9884\u6d4bCL\u4e4b\u6bd4\u4f5c\u4e3a\u6821\u6b63\u56e0\u5b50\u3002Collins\u7b49\u4eba\u5c06\u6b64\u6cd5\u7528\u4e8e3\u4e2a\u6297\u80bf\u7624\u836f\uff0c\u6bcf\u4e2a\u836f\u7684I\u671f\u8bd5\u9a8c\u7f29\u77ed\u4e8612\uff5e24\u4e2a\u6708\u2014\u2014\u8fd9\u6b63\u662fPK\u5bfc\u5411\u6cd5\u7684\u6838\u5fc3\u5438\u5f15\u529b\uff1a\u5408\u7406\u7684\u4eba\u4f53\u5242\u91cf\u9884\u4f30\u53ef\u4ee5\u76f4\u63a5\u780d\u6389\u591a\u4e2a\u5242\u91cf\u722c\u5761\u961f\u5217\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u4f46\u5b83\u6709\u4e24\u4e2a\u5185\u5d4c\u5047\u8bbe\uff1a\u2460\u53ea\u6709\u539f\u5f62\u836f\u6709\u6d3b\u6027\uff1b\u2461\u76f8\u540c\u8840\u836f\u6d53\u5ea6\u4e0b\uff0c\u836f\u7269\u5728\u4eba\u4e0e\u5176\u4ed6\u79cd\u5c5e\u4e2d\u4ea7\u751f\u76f8\u540c\u7684\u836f\u7406\/\u6bd2\u7406\u6548\u5e94\u3002\u7b2c\u4e8c\u4e2a\u5047\u8bbe\u6070\u6070\u5728TGN1412\u8fd9\u7c7b\u79cd\u5c5e\u654f\u611f\u6027\u5dee\u5f02\u5de8\u5927\u7684\u573a\u666f\u4e0b\u5931\u6548\u3002<\/p>\n\n\n\n<h6 class=\"wp-block-heading\"><strong>4<\/strong><strong>. PK\/PD\u5efa\u6a21\u6cd5<\/strong><\/h6>\n\n\n\n<p class=\"wp-block-paragraph\">Lowe\u7b49\u4eba\u63d0\u51fa\u7684\u56db\u6b65\u6cd5\u662f\u76ee\u524d\u516c\u8ba4\u7684\u7cfb\u7edf\u5316\u6846\u67b6\uff1a<\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li>\u901a\u8fc7\u4f53\u5916\/\u4f53\u5185\u836f\u7406\u5b9e\u9a8c\u5efa\u7acb\u6d53\u5ea6-\u6548\u5e94\u5173\u7cfb\uff0c\u786e\u5b9a\u751f\u7269\u6807\u5fd7\u7269\u4e0ePD\u53c2\u6570\uff08\u5982EC50\uff09\uff1b<\/li>\n\n\n\n<li>\u523b\u753b\u79cd\u5c5e\u5dee\u5f02\u2014\u2014\u7ec4\u7ec7\u5206\u5e03\u3001\u7ec4\u7ec7\/\u8840\u6d46\u86cb\u767d\u7ed3\u5408\u3001\u8840\u7ec6\u80de\u7ed3\u5408\u3001\u9776\u53d7\u4f53\u5360\u7528\u7684\u5dee\u5f02\uff1b<\/li>\n\n\n\n<li>\u9884\u6d4b\u4eba\u4f53PK\u53c2\u6570\uff08CL\u3001F\u3001\u8840\u836f\u6d53\u5ea6-\u65f6\u95f4\u66f2\u7ebf\uff09\uff1b<\/li>\n\n\n\n<li>\u6574\u5408\u4eba\u4f53PK\u4e0ePD\u6a21\u578b\uff0c\u6a21\u62df\u5242\u91cf-\u66b4\u9732-\u54cd\u5e94-\u65f6\u95f4\u8fc7\u7a0b\uff1a\u7b80\u5355\u60c5\u5f62\u7528\u9608\u503c\u6a21\u578b\uff08\u6d53\u5ea6\u7ef4\u6301\u5728EC50\u4e4b\u4e0a\u3001\u6bd2\u6027\u9608\u503c\u4e4b\u4e0b\uff09\uff0c\u590d\u6742\u60c5\u5f62\u7528\u5b8c\u6574PK\/PD\u4eff\u771f\u3002<\/li>\n<\/ol>\n\n\n\n<p class=\"wp-block-paragraph\">Heimbach\u7b49\u4eba\u8fdb\u4e00\u6b65\u628a\u5236\u5242\u4e0e\u751f\u7269\u836f\u5242\u5b66\u53c2\u6570\uff08\u5982BCS\u5206\u7c7b\uff09\u7eb3\u5165\u6a21\u578b\uff0c\u4f7f\u4e0d\u540c\u5242\u578b\u3001\u4e0d\u540c\u6eb6\u89e3\u7279\u6027\u836f\u7269\u7684PK\/PD\u6295\u5f71\u6210\u4e3a\u53ef\u80fd\uff0c\u5e76\u8bc1\u660e\u4ec5\u7528\u5355\u4e00\u79cd\u5c5e\u6570\u636e\u5373\u53ef\u5b8c\u6210\u4eba\u4f53PK\/PD\u6295\u5f71\u3002\u5bf9\u4e8e\u836f\u4ee3\u884c\u4e3a\u9ad8\u5ea6\u53ef\u9884\u6d4b\u7684\u5355\u514b\u9686\u6297\u4f53\uff08PK\u6027\u8d28\u7531\u4e9a\u578b\u51b3\u5b9a\u3001\u5747\u4e00\u6027\u597d\uff09\uff0cPK\/PD\u5efa\u6a21\u5c24\u5176\u6210\u529f\uff1b\u4ee5\u53ef\u4f53\u5916\u6d4b\u5b9a\u7684\u53d7\u4f53\u5360\u7528\uff08RO\uff09\u4e3a\u751f\u7269\u6807\u5fd7\u7269\u65f6\uff0c\u6fc0\u52a8\u5242\u8d77\u59cb\u5242\u91cf\u53d6\u4f4eRO\u3001\u62ee\u6297\u5242\u53ef\u53d6\u9ad8RO\u3002<\/p>\n\n\n\n<h5 class=\"wp-block-heading\"><strong>\u4e8c\u300117\u79cd\u4eba\u4f53\u6e05\u9664\u7387\u9884\u6d4b\u65b9\u6cd5<\/strong><\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">PK\/PD\u5bfc\u5411\u65b9\u6cd5\u7684\u7cbe\u5ea6\uff0c\u6700\u7ec8\u53d6\u51b3\u4e8e\u80fd\u5426\u51c6\u786e\u9884\u6d4b\u4e24\u4e2a\u5173\u952ePK\u53c2\u6570\uff1a\u6e05\u9664\u7387\uff08CL\uff09\u548c\u751f\u7269\u5229\u7528\u5ea6\uff08F\uff09\u300217\u79cd\u6e05\u9664\u7387\u9884\u6d4b\u65b9\u6cd5\u5206\u5c5e\u4e09\u5927\u95e8\u6d3e\uff1a\u79cd\u5c5e\u95f4\u5f02\u901f\u653e\u5927\uff08\u7ecf\u9a8c\u6d3e\uff09\u3001\u4f53\u5916-\u4f53\u5185\u5916\u63a8\uff08IVIVE\uff09\uff08\u673a\u5236\u6d3e\uff09\u4e0e\u8ba1\u7b97\u673a\u9884\u6d4b\uff08\u6570\u636e\u6d3e\uff09\u3002<\/p>\n\n\n\n<h6 class=\"wp-block-heading\"><strong>\u95e8\u6d3e\u4e00\uff1a\u5f02\u901f\u653e\u5927\u2014\u2014\u201c\u52a8\u7269\u5373\u5c0f\u53f7\u4eba\u7c7b\u201d<\/strong><\/h6>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2460<\/strong><strong>\u7b80\u5355\u5f02\u901f\u653e\u5927<\/strong><strong>\u3002<\/strong>\u5f02\u901f\u653e\u5927\u7684\u5e95\u5c42\u4fe1\u5ff5\u662f\uff1a\u89e3\u5256\u4e0e\u751f\u7406\u529f\u80fd\u5728\u54fa\u4e73\u52a8\u7269\u95f4\u9075\u5faa\u76f8\u4f3c\u7684\u89c4\u6a21\u6cd5\u5219\u3002\u6700\u57fa\u7840\u7684\u5f62\u5f0f\u662f\u7b80\u5355\u5f02\u901f\u653e\u5927\uff08SA\uff09\uff1a<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">CL = a \u00d7 W^b<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">W\u4e3a\u4f53\u91cd\uff0ca\u4e3a\u7cfb\u6570\uff0cb\u4e3a\u6307\u6570\uff1b\u81f3\u5c11\u9700\u8981\u4e24\u79cd\u52a8\u7269\u7684\u6570\u636e\u62df\u5408<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">SA\u7684\u9002\u7528\u6027\u9ad8\u5ea6\u4f9d\u8d56\u836f\u7269\u7684\u809d\u810f\u63d0\u53d6\u7387\u3002\u5bf9\u9ad8\u63d0\u53d6\u7387\u836f\u7269\uff0c\u809d\u6e05\u9664\u7387\u53d7\u809d\u8840\u6d41\u9650\u5236\uff0c\u800c\u809d\u8840\u6d41\u6070\u4e0e\u4f53\u91cd\u8de8\u79cd\u5c5e\u76f8\u5173\uff0c\u56e0\u6b64\u9884\u6d4b\u8f83\u51c6\u3002Tang\u7b49\u5bf957\u4e2a\u809d\u6d88\u9664\u836f\u7269\u7684\u5168\u666f\u5206\u6790\u663e\u793a\uff1a\u9884\u6d4b\u7cbe\u5ea6\u5448\u9ad8CL\uff08n=11\uff09\uff1e\u4e2dCL\uff08n=17\uff09\uff1e\u4f4eCL\uff08n=29\uff09\u7684\u68af\u5ea6\u3002\u5bf9\u6cbb\u7597\u6027\u86cb\u767d\uff08n=10\uff09\uff0cSA\u7684\u53ef\u9760\u6027\u4e5f\u663e\u8457\u4f18\u4e8e\u5c0f\u5206\u5b50\uff08n=102\uff09\u3002\u4e00\u4e2a\u91cd\u8981\u7684\u65b9\u6cd5\u8bba\u6559\u8bad\uff1a\u591a\u6570\u5f02\u901f\u653e\u5927\u7814\u7a76\u559c\u6b22\u62a5\u544a\u51b3\u5b9a\u7cfb\u6570r\u00b2\u6765\u5c55\u793a\u62df\u5408\u4f18\u5ea6\uff0c\u4f46Tang\u4e0eMayersohn\u7528\u6570\u5b66\u6a21\u578b\u548c\u6587\u732e\u6570\u636e\u8bc1\u660e\u2014\u2014r\u00b2\u4e0e\u4eba\u4f53CL\u9884\u6d4b\u51c6\u786e\u6027\u4e4b\u95f4\u5e76\u65e0\u76f8\u5173\u5173\u7cfb\u3002\u66f2\u7ebf\u62df\u5408\u5f97\u597d\uff0c\u4e0d\u7b49\u4e8e\u5916\u63a8\u5f97\u51c6\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2461<\/strong><strong> \u6e38\u79bb\u578bCL\u6362\u7b97\u3002<\/strong>\u7531\u4e8e\u8840\u6d46\u86cb\u767d\u7ed3\u5408\u5b58\u5728\u663e\u8457\u79cd\u5c5e\u5dee\u5f02\u3001\u4e14\u53ea\u6709\u6e38\u79bb\u578b\u836f\u7269\u624d\u80fd\u88ab\u6d88\u9664\uff0c\u5bf9\u6e38\u79bbCL\uff08CL<sub>u<\/sub>\uff09\u505a\u5f02\u901f\u653e\u5927\u7406\u8bba\u4e0a\u66f4\u5408\u7406\u3002Obach\u7b49\u5bf914\u4e2a\u836f\u7269\u7684\u56de\u987e\u5206\u6790\uff1a\u603bCL\u9884\u6d4b\u5e73\u5747\u500d\u6570\u8bef\u5dee\uff08AFE\uff091.91\u300164%\u843d\u5728\u4e24\u500d\u8bef\u5dee\u5185\uff1b\u6e38\u79bbCL\u5219\u4e3aAFE 1.79\u300169%\u2014\u2014\u6539\u5584\u771f\u5b9e\u4f46\u5e45\u5ea6\u6709\u9650\u3002\u53e6\u4e00\u987924\u4e2a\u5316\u5408\u7269\u7684\u7814\u7a76\u5bf9\u6bd4\u66f4\u60ac\u6b8a\uff1aSA\u4ec517%\u843d\u5728\u4e24\u500d\u8bef\u5dee\u5185\uff0c\u6e38\u79bbCL\u6cd5\u5219\u8fbe62%\u3002\u4e0d\u8fc7\u82e5\u4ee530%\u8bef\u5dee\u4e3a\u6210\u529f\u7ebf\uff0c\u4e24\u8005\u65e0\u663e\u8457\u5dee\u5f02\uff0c\u5224\u5b9a\u6807\u51c6\u7684\u9009\u62e9\u5bf9\u4e8e\u8bc4\u4f30\u4e0d\u540c\u65b9\u6cd5\u7684\u53ef\u9884\u6d4b\u6027\u81f3\u5173\u91cd\u8981\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2462<\/strong><strong>\u4e8c\u9879\u5f0f\u5e42\u65b9\u7a0b<\/strong><strong>\u3002<\/strong>\u9488\u5bf9\u4f4e\u809d\u63d0\u53d6\u836f\u7269(\u5176CL\u4e0e\u4f53\u91cd\u4e0d\u76f8\u5173)\uff0cBoxenbaum &amp;Fertig\u5c06\u4eba\u4f53CL\u4e0e\u8111\u91cd\u91cf(BrW)\u3001\u6700\u5927\u5bff\u547d\u6f5c\u80fd(MLP)\u5173\u8054\uff1b\u6216\u4ee5CL\u00d7MLP\u4e0e\u4f53\u91cd\u505a\u5f02\u901f\u653e\u5927\u3002\u76f8\u5173\u9884\u6d4b\u7814\u7a76\u8f83\u5c11\uff0c\u4e0d\u5e38\u7528\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2463<\/strong><strong> \u6307\u6570\u6cd5\u5219\uff08RoE\uff09\u3002<\/strong>Mahmood\u4e0eBalian\u57fa\u4e8e50\u4e2a\u836f\u7269\uff08\u22653\u79cd\u5c5e\uff09\u7684\u6570\u636e\uff0c\u6839\u636eSA\u6307\u6570b\u7684\u5927\u5c0f\u5f15\u5165\u8111\u91cd\uff08BrW\uff09\u6216\u6700\u5927\u5bff\u547d\u6f5c\u80fd\uff08MLP\uff09\u6821\u6b63\u3002\u539f\u59cb\u9a8c\u8bc1\u4e2d\uff0c45\u4e2a\u836f\u7269\u670942\u4e2a\u843d\u5728\u4e24\u500d\u8bef\u5dee\u5185\uff0c\u4f18\u4e8eSA\u768435\/45\u3002\u540e\u7eed68\u4e2a\u5316\u5408\u7269\u7684\u7814\u7a76\u4e5f\u652f\u6301RoE\u4f18\u4e8e\u5176\u4ed6\u5f02\u901f\u65b9\u6cd5\u3001\u4e0eIVIVE\u76f8\u5f53\uff08\u5c24\u5176\u5bf9\u4f4e\u8102\u6eb6\u6027\u3001\u4e2d\u9ad8\u6e05\u9664\u7387\u5316\u5408\u7269\uff09\u3002\u4f46Nagilla\u4e0eWard\u7528103\u4e2a\u5316\u5408\u7269\u7684\u5927\u6570\u636e\u96c6\u53d1\u73b0\u6240\u6709\u6821\u6b63\u56e0\u5b50\uff08BrW\u3001MLP\u3001GFR\u3001UDPGT\u3001\u80c6\u6c41\u6d41\u7387\uff09\u90fd\u4e0d\u80fd\u6539\u5584\u9884\u6d4b\u2014\u2014RoE\u7684\u6027\u80fd\u5b58\u7591\uff0c\u53ef\u80fd\u9ad8\u5ea6\u4f9d\u8d56\u6570\u636e\u96c6\u6784\u6210\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2464<\/strong><strong> \u80be\/\u80c6\u6392\u6cc4\u836f\u7269\u7684\u6821\u6b63\u653e\u5927\u3002<\/strong>\u80be\u810f\u6e05\u9664\u6d89\u53ca\u6ee4\u8fc7\u3001\u91cd\u5438\u6536\u4e0e\u4e3b\u52a8\u5206\u6ccc\u4e09\u79cd\u673a\u5236\uff0cSA\u5bf9\u9ad8\u80be\u6e05\u9664\u836f\u7269\u5e38\u5e38\u5931\u7075\u3002Mahmood\u63d0\u51fa\u4ee5GFR\u3001\u80be\u8840\u6d41\u91cf\u3001\u80be\u91cd\u6216\u80be\u91cd\u91cf\u4e3a\u6821\u6b63\u56e0\u5b50\uff1b\u5bf9\u80c6\u6c41\u6392\u6cc4\u836f\u7269\u5219\u4ee5\u80c6\u6c41\u6d41\u7387\u6216UDPGT\u9176\u6d3b\u6027\u6821\u6b63\u3002\u4e24\u4e2a\u6570\u636e\u96c6\u867d\u5c0f\uff08n=8\u548cn=10\uff09\uff0c\u4f46\u5747\u663e\u793a\u4f18\u4e8eSA\u548cRoE\u3002\u80a0\u809d\u5faa\u73af\u836f\u7269\u4ecd\u662f\u9884\u6d4b\u7684\u786c\u9aa8\u5934\u2014\u2014\u79cd\u5c5e\u95f4\u809d\u80c6\u8f6c\u8fd0\u4f53\u8868\u8fbe\u7684\u5dee\u5f02\u6240\u77e5\u751a\u5c11\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2465<\/strong><strong> \u4f53\u5916\u56fa\u6709\u6e05\u9664\u7387\u5f52\u4e00\u5316\u3002<\/strong>Lave\u7b49\u7528\u52a8\u7269\u4e0e\u4eba\u7684\u4f53\u5916\u56fa\u6709CL\u6821\u6b63\u52a8\u7269\u4f53\u5185CL\u540e\u518d\u505a\u5f02\u901f\u653e\u5927\uff0c11\u4e2a\u809d\u6d88\u9664\u836f\u7269\u4e2d9\u4e2a\uff0882%\uff09\u843d\u5728\u4e24\u500d\u8bef\u5dee\u5185\uff0c\u5e73\u5747\u6298\u53e0\u8bef\u5deeAFE\u4e3a 1.6\u500d\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2466<\/strong><strong> \u591a\u6307\u6570\u5f02\u901f\uff08MA\uff09\u3002<\/strong>\u4e3a\u6d88\u9664\u201c\u9009\u54ea\u4e2a\u6821\u6b63\u56e0\u5b50\u201d\u7684\u4e0d\u786e\u5b9a\u6027\uff0cGoteti\u7b49\u5047\u8bbeCL\u540c\u65f6\u5173\u8054\u4f53\u91cd\u4e0e\u6d88\u9664\u5668\u5b98\uff08\u809d\u3001\u80be\uff09\u4f53\u79ef\uff1aCL = a\u00d7W^b + c\u00d7W^d\uff0c\u5176\u4e2d\u5668\u5b98\u4f53\u79ef\u5bf9\u4f53\u91cd\u7684\u659c\u7387\u7ea6\u4e3a0.9\uff0c\u6545d\u56fa\u5b9a\u4e3a0.9\u3002\u8bad\u7ec3\u96c676%\u4e24\u500d\u5185\u8bef\u5dee\uff1b\u6d4b\u8bd5\u96c654%\u4e24\u500d\u5185\u8bef\u5dee\u2014\u2014\u4f18\u4e8eSA\u3001\u7565\u900a\u4e8eRoE\uff1b\u4f46\u5f53SA\u6307\u6570b\uff1c0.7\u65f6\uff0cSA\u53cd\u800c\u66f4\u51c6\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2467<\/strong><strong> \u809d\u8840\u6d41\u6cd5\uff08LBF\uff09\u3002<\/strong>\u7528\u79cd\u5c5e\u95f4\u809d\u8840\u6d41\u6bd4\u503c\u76f4\u63a5\u5916\u63a8\u3002Ward\u4e0eSmith\u5bf9103\u4e2a\u836f\u7269\u7684\u7efc\u5408\u8bc4\u4f30\uff1a\u7334LBF\u6cd5\u662f\u6700\u51c6\u7684\u5355\u9879\u65b9\u6cd5\uff0872%\u4e24\u500d\u5185\uff09\uff0c\u4f18\u4e8e\u4e09\u7269\u79cd\u53ca\u4e24\u7269\u79cd\u7684\u5404\u79cd\u5f02\u901f\u653e\u5927\uff0862%\uff5e66%\uff09\uff0c\u4e5f\u4f18\u4e8e\u5927\u9f20LBF\u548c\u72acLBF\uff08\u5747\u4e3a66%\uff09\u3002\u540e\u7eed\u7814\u7a76\u8fdb\u4e00\u6b65\u53d1\u73b0\u5c0f\u9f20\u4e0e\u7334LBF\u4f18\u4e8e\u5927\u9f20\u4e0e\u72acLBF\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2468<\/strong><strong> \u4e00\/\u4e24\u79cd\u5c5e\u5916\u63a8\u3002<\/strong>Tang\u7b49\u57fa\u4e8e102\u4e2a\u836f\u7269\u7684\u6570\u636e\u5e93\uff0c\u76f4\u63a5\u7ed9\u51fa\u4e86\u4ece\u5355\u4e00\u7269\u79cd\uff08\u5927\u9f20\u3001\u72ac\u6216\u7334\uff09\u6216\u4e24\u7269\u79cd\u7ec4\u5408\u5916\u63a8\u4eba\u7684\u56fa\u5b9a\u7cfb\u6570\u7ecf\u9a8c\u65b9\u7a0b\uff08\u5982CL<sub>human <\/sub>= 0.152\u00d7CL<sub>rat<\/sub>\uff0c0.410\u00d7CL<sub>dog<\/sub>\uff0c0.407\u00d7CL<sub>monkey<\/sub>\uff0c\u5355\u4f4d\u5747\u4e3akg\u89c4\u683c\uff09\u3002\u572826\u4e2a\u5316\u5408\u7269\u7684\u6d4b\u8bd5\u96c6\u4e2d\uff0c\u6027\u80fd\u81f3\u5c11\u4e0eRoE\/SA\u76f8\u5f53\u3002\u4f46Mahmood\u752845\u4e2a\u836f\u7269\u7684\u6570\u636e\u63d0\u51fa\u5f02\u8bae\u2014\u2014RoE\u4ecd\u66f4\u4f18\u3002\u4e89\u8bae\u7684\u4eae\u70b9\u5728UGT\u4ee3\u8c22\u9176\u5e95\u7269\uff1a12\u4e2aUGT\u836f\u7269\u7684\u5bf9\u6bd4\u4e2d\uff0c\u7334\u5355\u79cd\u5c5e\u5916\u63a8\uff08\u56fa\u5b9a\u6307\u65700.75\uff09\u4f18\u4e8eRoE\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2469<\/strong><strong> \u5782\u76f4\u5f02\u901f\u4e0eFCIM\u3002<\/strong>\u90e8\u5206\u5316\u5408\u7269\u7ecf\u5f02\u901f\u653e\u5927\u540e\u4eba\u4f53CL\u88ab\u4e25\u91cd\u9ad8\u4f30\uff08\u53ef\u8fbe\u6570\u5341\u500d\uff09\uff0c\u79f0\u4e3a\u201c\u5782\u76f4\u5f02\u901f\u201d\u3002Tang\u4e0eMayersohn\u7ed9\u51fa\u4e86\u8bc6\u522b\u6807\u51c6\uff1aClogP\uff1e2\u3001\u5927\u9f20\u4e0e\u4eba\u8840\u6d46\u6e38\u79bb\u5206\u6570\u4e4b\u6bd4R<em>f<\/em><sub><em>u<\/em><\/sub>\uff1e5\u3001\u7ecf\u4ee3\u8c22\u6d88\u9664\u3002\u8bc6\u522b\u4e4b\u540e\u8fdb\u4e00\u6b65\u5efa\u7acb\u4e86<em>fu<\/em>\u6821\u6b63\u622a\u8ddd\u6cd5\uff08FCIM\uff09\uff1a<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">CL = 33.35mL\/min \u00d7 (a \/ R<em>fu<\/em>)^0.77<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">a\u4e3aSA\u7cfb\u6570\uff0cR<em>f<\/em><sub><em>u<\/em><\/sub>\u4e3a\u5927\u9f20\/\u4eba\u8840\u6d46\u6e38\u79bb\u5206\u6570\u6bd4<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u5b9e\u7528\u7b56\u7565\uff1aSA\u6307\u6570b\uff1c0.5\u6216b\uff1e1.2\u65f6\u7528FCIM\uff0c0.5\uff1cb\uff1c1.2\u65f6\u7528\u6e38\u79bbCL\u6cd5\uff0c\u4e24\u500d\u8bef\u5dee\u7387\u53ef\u8fbe79%\u3002<\/p>\n\n\n\n<h6 class=\"wp-block-heading\"><strong>\u95e8\u6d3e\u4e8c\uff1aIVIVE\u2014\u2014\u4ece\u8bd5\u7ba1\u76f4\u63a5\u5916\u63a8\u5230\u4eba\u4f53<\/strong><\/h6>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2460 <\/strong><strong>\u57fa\u4e8e\u751f\u7406\u5b66\u653e\u5927\u56e0\u5b50(PB-SF)\u7684\u7ecf\u5178IVIVE<\/strong><strong>\u3002<\/strong>IVIVE\u7684\u54f2\u5b66\u5b8c\u5168\u4e0d\u540c\uff1a\u4e0d\u4f9d\u8d56\u52a8\u7269\u4f53\u5185\u6570\u636e\uff0c\u800c\u662f\u7528\u4eba\u6e90\u4f53\u5916\u7cfb\u7edf\uff08\u809d\u5fae\u7c92\u4f53\u3001\u809d\u7ec6\u80de\u3001\u91cd\u7ec4CYP450\u9176\uff09\u6d4b\u5f97\u56fa\u6709\u6e05\u9664\u7387\uff0c\u518d\u7528\u751f\u7406\u5b66\u653e\u5927\u56e0\u5b50\u6362\u7b97\u809d\u810f\u6e05\u9664\u7387\uff08CL<sub>H<\/sub>\uff09\uff1a<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>\u751f\u7406\u5b66\u653e\u5927\u56e0\u5b50\uff08PB-SF\uff09\uff1a\u6bcf\u5343\u514b\u4f53\u91cd3.1\u00d710\u2079\u4e2a\u809d\u7ec6\u80de\uff081.2\u00d710<sup>8<\/sup>\u7ec6\u80de\/\u514b\u00a0\u809d\u00d725.7\u514b\u809d\/\u5343\u514b\u00a0\u4f53\u91cd\uff09\u62161028 mg\u809d\u5fae\u7c92\u4f53\uff1b<\/li>\n\n\n\n<li>\u809d\u5904\u7f6e\u6a21\u578b\uff1awell-stirred\uff08\u5145\u5206\u6405\u62cc\uff0c\u56e0\u8ba1\u7b97\u7b80\u4fbf\u6700\u5e38\u7528\uff09\u3001parallel tube\uff08\u5e76\u884c\u7ba1\uff09\u3001dispersion\uff08\u5f25\u6563\uff09\u2014\u2014\u540e\u4e24\u8005\u9884\u6d4b\u7cbe\u5ea6\u76f8\u8fd1\u4e14\u5747\u4f18\u4e8ewell-stirred\uff1b\u9ad8\u6e05\u9664\u7387\u836f\u7269\u4ee5dispersion\u6a21\u578b\u6700\u53ef\u9760\u3002<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">\u7136\u800c\u201c\u88f8\u201dIVIVE\u6709\u4e00\u4e2a\u8457\u540d\u7684\u7cfb\u7edf\u6027\u95ee\u9898\uff1a\u4f4e\u9884\u6d4b\u3002Ito\u4e0eHouston\u7528\u809d\u5fae\u7c92\u4f53\u6570\u636e\u9884\u6d4b55\u4e2a\u5316\u5408\u7269\uff0cCL<sub>int,<\/sub><sub>&nbsp;<\/sub><sub>in vivo<\/sub>\u5e73\u5747\u88ab\u4f4e\u4f309\u500d\uff1bBrown\u7b49\u7528\u809d\u7ec6\u80de\u6570\u636e\uff0c\u4ecd\u5e73\u5747\u4f4e\u4f304.5\u500d\u3002Chiba\u7b49\u603b\u7ed3\u4e86\u56db\u4e2a\u539f\u56e0\uff1a\u4f53\u5916\u7ec4\u7ec7\u5236\u5907\u4e0e\u50a8\u5b58\u8fc7\u7a0b\u635f\u5931\u4ee3\u8c22\u6d3b\u6027\uff1b\u809d\u5916\u4ee3\u8c22\uff08\u80a0\u3001\u80be\uff09\u8d21\u732e\u88ab\u5ffd\u7565\uff1b\u836f\u7269\u4e0e\u5fae\u7c92\u4f53\u8102\u8d28\/\u7ec6\u80de\u6210\u5206\u7684\u975e\u7279\u5f02\u6027\u7ed3\u5408\u672a\u6821\u6b63\uff1b\u809d\u6444\u53d6\u8f6c\u8fd0\u4f53\u4ecb\u5bfc\u7684\u6e05\u9664\u88ab\u4f4e\u4f30\u2014\u2014\u8f6c\u8fd0\u4f53\u5e95\u7269\u7684\u4f4e\u4f30\u5c24\u5176\u4e25\u91cd\u3002\u7531\u6b64\u884d\u751f\u51fa\u4e00\u7cfb\u5217\u6821\u6b63\u7b56\u7565\uff1a<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2461<\/strong><strong>\u836f\u7269\u7279\u5f02\u6027\u653e\u5927\u56e0\u5b50\u6821\u6b63\u7684IVIVE<\/strong><strong>\u3002<\/strong>\u7528\u540c\u4e00\u836f\u7269\u5728\u52a8\u7269\u4f53\u5185\u7684CL<sub>int,in vivo<\/sub><sub>&nbsp;<\/sub>\/<sub>&nbsp;<\/sub>C<sub>Lint,in vitro<\/sub>\u6bd4\u503c\u4f5c\u4e3a\u6821\u6b63\u3002Ito\u4e0eHouston\uff0833\u4e2a\u5316\u5408\u7269\uff0c\u5927\u9f20\uff09\u5c06AFE\u4ece6.17\u964d\u52302.33\uff0c\u4e24\u500d\u5185\u547d\u4e2d\u7387\u4ece15.2%\u5347\u81f339.4%\uff1bNaritomi\u7b49\uff088\u4e2a\u836f\u7269\uff0c\u5927\u9f20\/\u72ac\u56e0\u5b50\uff09\u5c06AFE\u4ece4.02\u964d\u81f31.57\/1.68\uff0c\u4e24\u500d\u5185\u547d\u4e2d\u7387\u4ece25%\u8dc3\u5347\u81f369%\/77%\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2462<\/strong><strong>\u7ecf\u9a8c\u653e\u5927\u56e0\u5b50\u6821\u6b63\u7684IVIVE<\/strong><strong>\u3002<\/strong>\u4e0d\u7528\u52a8\u7269\u5b9e\u9a8c\uff0c\u76f4\u63a5\u56de\u5f52\u4ebaCL<sub>int,in vivo<\/sub>\u4e0eCL<sub>int,in vitro<\/sub>\u5f97\u5230\u5e73\u5747\u7cfb\u6570\u3002Lave\u7b49\u5c06\u5176\u7eb3\u5165\u540e\uff0c\u4e24\u500d\u5185\u547d\u4e2d\u7387\u4ece15.2%\u5347\u81f345.5%\uff08n=33\uff09\uff1bZuegge\u7b49\u62a5\u544aAFE\u4ece2.01\u964d\u81f31.64\u3001\u4e09\u500d\u5185\u547d\u4e2d\u7387\u4ece77.3%\u5347\u81f395.5%\u3002Fagerholm\u8fdb\u4e00\u6b65\u6309\u836f\u7269\u7c7b\u522b\uff08\u9178\/\u78b1\/\u4e2d\u6027\u00d7\u4f4e\/\u9ad8CLint\uff09\u5206\u7ec4\u5efa\u7acb\u7c7b\u522b\u7279\u5f02\u6027\u56e0\u5b50\uff08CD-SF\uff09\uff0c\u8fbe\u5230AFE 1.3\u3001\u4e24\u500d\u518576%\uff08n=29\uff09\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2463<\/strong><strong>\u86cb\u767d\u7ed3\u5408\u6821\u6b63\u7684IVIVE<\/strong><strong>\u3002<\/strong>\u53ea\u6709\u6e38\u79bb\u836f\u7269\u624d\u80fd\u88ab\u4ee3\u8c22\uff0c\u56e0\u6b64\u7eb3\u5165\u8840\u6d46\u6e38\u79bb\u5206\u6570<em>f<\/em><sub><em>u,p<\/em><\/sub>\u3001\u5fae\u7c92\u4f53\u6e38\u79bb\u5206\u6570<em>f<\/em><sub><em>u,micro<\/em><\/sub>\u6216\u809d\u7ec6\u80de\u6e38\u79bb\u5206\u6570<em>f<\/em><sub><em>u,hepa<\/em><\/sub>\u3002Obach\u5bf929\u4e2a\u5316\u5408\u7269\u7684\u7ecf\u5178\u5206\u6790\u7ed9\u51fa\u4e86\u7cbe\u7ec6\u7684\u7ed3\u8bba\uff1a\u78b1\u6027\u548c\u4e2d\u6027\u5316\u5408\u7269\u4ec5\u6821\u6b63<em>f<\/em><sub><em>u,p<\/em><\/sub>\u53cd\u800c\u9884\u6d4b\u53d8\u5dee\uff0c\u9700\u540c\u65f6\u6821\u6b63<em>f<\/em><sub><em>u,p<\/em><\/sub>\u4e0e<em>f<\/em><sub><em>u,micro<\/em><\/sub>\uff1b\u9178\u6027\u5316\u5408\u7269\u5219\u5fc5\u987b\u53cc\u91cd\u6821\u6b63\u624d\u53ef\u9760\u3002\u53e6\u4e00\u5de7\u5999\u505a\u6cd5\uff1a\u5728\u5fae\u7c92\u4f53\u5b75\u80b2\u6db2\u4e2d\u76f4\u63a5\u52a0\u5165\u4eba\u8840\u6d46\uff0c\u4e24\u500d\u5185\u547d\u4e2d\u7387\u4ece57%\u63d0\u9ad8\u523071%\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2464<\/strong><strong>\u91cd\u7ec4\u9176(\u5355\u4e2a\u4ee3\u8c22\u9176)IVIVE<\/strong><strong>\u3002<\/strong>\u7528\u91cd\u7ec4\u4ebaCYP450\u9176\u66ff\u4ee3\u809d\u5fae\u7c92\u4f53\/\u809d\u7ec6\u80de\uff0c\u901a\u8fc7\u76f8\u5bf9\u4e30\u5ea6\u6cd5\uff08\u6309\u514d\u75ab\u5b9a\u91cf\u86cb\u767d\u6c34\u5e73\u52a0\u6743\uff09\u6216\u76f8\u5bf9\u6d3b\u6027\u56e0\u5b50\u6cd5\uff08RAF\uff09\u6574\u5408\u5404\u540c\u5de5\u9176\u8d21\u732e\u3002Stringer\u7b49\u5bf972\u4e2a\u836f\u7269\u7684\u8bc4\u4f30\uff1a\u91cd\u7ec4\u9176AFE 1.53\uff0c\u663e\u8457\u4f18\u4e8e\u809d\u5fae\u7c92\u4f53\uff08AFE 2.32, n=41\uff09\u548c\u809d\u7ec6\u80de\uff08AFE 5.21, n=57\uff09\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2465<\/strong><strong>\u80be\u6e05\u9664\u7387\u7684\u751f\u7406\u5b66\u9884\u6d4b\u6cd5<\/strong><strong>\u3002<\/strong>\u4e0a\u8ff0IVIVE\u5747\u4e0d\u9002\u7528\u4e8e\u80be\u6392\u6cc4\u836f\u7269\u3002Fagerholm\u57fa\u4e8e\u4f53\u5916\u88ab\u52a8\u6e17\u900f\u6027\uff08Pe\uff09\u5efa\u7acb\u6e17\u900f\u6027\u5206\u7c7b\u7cfb\u7edf\uff0c\u7528GFR\u3001\u80be\u8840\u6d41\u91cf\u3001<em>f<\/em><sub><em>u,p<\/em><\/sub>\u3001\u91cd\u5438\u6536\u5206\u6570\u63a8\u7b97\u80be\u6e05\u9664\uff0c\u4f46\u5c1a\u672a\u7ecf\u5927\u89c4\u6a21\u6570\u636e\u96c6\u9a8c\u8bc1\u3002<\/p>\n\n\n\n<h6 class=\"wp-block-heading\"><strong>\u95e8\u6d3e\u4e09\uff1a\u8ba1\u7b97\u673a\u9884\u6d4b\u2014\u2014\u5206\u5b50\u7ed3\u6784\u76f4\u901a\u4eba\u4f53CL<\/strong><\/h6>\n\n\n\n<p class=\"wp-block-paragraph\">\u7eafin silico\u65b9\u6cd5\uff08MLR\u591a\u5143\u7ebf\u6027\u56de\u5f52\u3001PLS\u504f\u6700\u5c0f\u4e8c\u4e58\u3001ANN\u4eba\u5de5\u795e\u7ecf\u7f51\u7edc\u3001kNN k\u8fd1\u90bb\uff09\u53ea\u9700\u5206\u5b50\u63cf\u8ff0\u7b26\u5373\u53ef\u9884\u6d4b\uff0c\u80fd\u5728\u5316\u5408\u7269\u672a\u5408\u6210\u4e4b\u524d\u5b8c\u6210\u865a\u62df\u7b5b\u9009\u2014\u2014\u8fd9\u662f\u6240\u6709\u5b9e\u9a8c\u65b9\u6cd5\u505a\u4e0d\u5230\u7684\u3002Wajima\u7b49\u7528\u5927\u9f20\/\u72acCL\u3001\u5206\u5b50\u91cf\u3001ClogP\u3001\u6c22\u952e\u53d7\u4f53\u6570\u5efa\u7acb\u7684MLR\u65b9\u7a0b\u58f0\u79f0\u4f18\u4e8e\u5f02\u901f\u653e\u5927\uff0c\u4f46\u88abMahmood\u6307\u51fa\u8bad\u7ec3\u96c6\u4e0e\u8bc4\u4f30\u96c6\u662f\u540c\u4e00\u6279\u6570\u636e\uff0c\u5c5e\u4e8e\u5faa\u73af\u8bba\u8bc1\u3002Yu\u5efa\u7acb\u7684kNN\u6a21\u578b\uff08370\u4e2a\u5316\u5408\u7269\u8bad\u7ec3\u300192\u4e2a\u6d4b\u8bd5\uff09\u6d4b\u8bd5\u96c6\u5e73\u5747\u843d\u5728\u4e24\u500d\u8bef\u5dee\u5185\uff0c\u7528\u4e8e\u6587\u732e\u4e2d20\u4e2a\u836f\u7269\u65f6\u900a\u4e8eRoE\u3001\u4f18\u4e8eSA\u3002\u603b\u4f53\u800c\u8a00\uff0c\u8fd9\u7c7b\u201c\u9ed1\u7bb1\u201d\u65b9\u6cd5\u9002\u5408\u65e9\u671f\u9ad8\u901a\u91cf\u7c97\u7b5b\uff0c\u4e0d\u80fd\u4f5c\u4e3aFIH\u5242\u91cf\u51b3\u7b56\u7684\u72ec\u7acb\u4f9d\u636e\u3002<\/p>\n\n\n\n<h5 class=\"wp-block-heading\"><strong>\u4e09\u3001\u751f\u7269\u5229\u7528\u5ea6\u9884\u6d4b<\/strong><\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">\u53e3\u670d\u662f\u6700\u53d7\u9752\u7750\u7684\u7ed9\u836f\u9014\u5f84\uff0c\u4f46\u5927\u91cf\u5019\u9009\u5206\u5b50\u6070\u6070\u5012\u5728\u751f\u7269\u5229\u7528\u5ea6\u8fd9\u4e00\u5173\u3002\u751f\u7269\u5229\u7528\u5ea6\u53ef\u62c6\u89e3\u4e3a\u4e09\u4e2a\u73af\u8282\u7684\u4e58\u79ef\uff1a<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">F = F<sub>A<\/sub> \u00d7 F<sub>G<\/sub> \u00d7 F<sub>H<\/sub><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">F<sub>A<\/sub>\uff1a\u5438\u6536\u5206\u6570\uff1bF<sub>G<\/sub>\uff1a\u9003\u8fc7\u80a0\u9053\u9996\u8fc7\u4ee3\u8c22\u7684\u5206\u6570\uff1bF<sub>H<\/sub>\uff1a\u9003\u8fc7\u809d\u810f\u9996\u8fc7\u4ee3\u8c22\u7684\u5206\u6570\uff08F<sub>H<\/sub> = 1 \u2212 CL<sub>H<\/sub>\/Q<sub>H<\/sub>\uff09<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u7531\u4e8e\u80a0\u9053CYP\u9176\u542b\u91cf\u4f4e\u3001\u80a0\u9053\u8840\u6d41\u91cf\u5c0f\uff0c\u80a0\u9053\u4ee3\u8c22\u4e00\u822c\u53ef\u5ffd\u7565\u2014\u2014\u4f46\u5bf9\u7ed3\u5408\u53cd\u5e94\u5e95\u7269\uff08\u786b\u9178\u5316\/\u8461\u8404\u7cd6\u919b\u9178\u5316\uff09\u4e0eCYP3A4\u5e95\u7269\u4f8b\u5916\uff0cF<sub>G<\/sub>\u53ef\u80fd\u6210\u4e3a\u51b3\u5b9a\u6027\u74f6\u9888\u3002\u76d8\u70b9\u4e866\u7c7b\u9884\u6d4b\u5de5\u5177\uff1a<\/p>\n\n\n\n<h6 class=\"wp-block-heading\"><strong>\u4f53\u5916\u4e09\u4ef6\u5957\uff1aCaco-2\u3001PAMPA\u3001IAM<\/strong><\/h6>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2460 Caco-2\u5355\u5206\u5b50\u5c42\u3002<\/strong>\u4eba\u7ed3\u80a0\u817a\u764c\u7ec6\u80de\u5728\u8de8\u5b54\u819c\u4e0a\u957f\u6210\u81f4\u5bc6\u5355\u5c42\uff0c\u6d4b\u5f97\u8868\u89c2\u6e17\u900f\u7cfb\u6570P<sub>app<\/sub>\u3002Artursson\u4e0eKarlsson\u7684\u7ecf\u5178\u7814\u7a76\u663e\u793a\u5176\u4e0e\u4eba\u4f53\u80a0\u9053\u5438\u6536\u9ad8\u5ea6\u76f8\u5173\uff08n=35\uff0cr=0.95\uff09\uff0c\u5e76\u6709\u7ecf\u9a8c\u65b9\u7a0b\uff1aF<sub>A<\/sub>% = 1.95\u00d7ln(P<sub>app<\/sub>) + 24.4\u3002\u77ed\u677f\uff1a\u4e3b\u52a8\u8f6c\u8fd0\u4f53\u5728Caco-2\u4e2d\u8868\u8fbe\u5931\u5e38\uff0c\u65e0\u6cd5\u53ef\u9760\u9884\u6d4b\u4e3b\u52a8\u8f6c\u8fd0\u836f\u7269\u7684\u5438\u6536\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2461 PAMPA\uff08\u5e73\u884c\u4eba\u5de5\u819c\u6e17\u900f\uff09\u3002<\/strong>\u4eff\u80a0\u9053\u5237\u72b6\u7f18\u819c\u8102\u8d28\u7ec4\u6210\u7684\u6ee4\u819c\u652f\u6491\u4eba\u5de5\u819c\u7cfb\u7edf\uff0c\u4e0eCaco-2\u7684F<sub>A<\/sub>\u9884\u6d4b\u7cbe\u5ea6\u76f8\u5f53\uff0c\u4f46\u901a\u91cf\u66f4\u9ad8\u3001\u6210\u672c\u66f4\u4f4e\uff1b\u540c\u6837\u53ea\u80fd\u8bc4\u4f30\u88ab\u52a8\u8de8\u7ec6\u80de\u6e17\u900f\uff0c\u5bf9\u65c1\u8def\u8f6c\u8fd0\u548c\u4e3b\u52a8\u8f6c\u8fd0\u65e0\u80fd\u4e3a\u529b\u3002<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u2462 IAM\u8272\u8c31\u3002<\/strong>\u7845\u80f6\u7c92\u8868\u9762\u5171\u4ef7\u63a5\u679d\u78f7\u8102\u5355\u5c42\uff0c\u6a21\u62df\u7ec6\u80de\u819c\u8102\u73af\u5883\uff0c\u4ee5\u5bb9\u91cf\u56e0\u5b50K\u2032<sub>IAM<\/sub>\u4e0e\u5438\u6536\u5206\u6570\u5efa\u7acb\u5b9a\u91cf\u5173\u7cfb\u3002\u5b9a\u4f4d\u4e0ePAMPA\u7c7b\u4f3c\u3002<\/p>\n\n\n\n<h6 class=\"wp-block-heading\"><strong>\u4f53\u5185\u65b9\u6cd5<\/strong><\/h6>\n\n\n\n<p class=\"wp-block-paragraph\">\u8fd9\u662f\u6587\u732e\u4e2d\u6781\u5177\u8b66\u793a\u610f\u4e49\u7684\u4e00\u7ec4\u6570\u636e\uff1aCao\u7b49\u53d1\u73b0\u5927\u9f20\u4e0e\u4eba\u5c0f\u80a0\u836f\u7269\u6e17\u900f\u6027\u76f8\u5173\u6027\u826f\u597d\uff08r\u00b2=0.8\uff09\uff0c\u4f46\u53e3\u670d\u751f\u7269\u5229\u7528\u5ea6\u51e0\u4e4e\u65e0\u5173\uff08r\u00b2=0.29\uff09\u2014\u2014\u7f6a\u9b41\u662f\u80a0\u9053\u4ee3\u8c22\u9176\u8868\u8fbe\u7684\u79cd\u5c5e\u5dee\u5f02\u3002Akabane\u7b49\u8fdb\u4e00\u6b65\u53d1\u73b0\uff0c13\u4e2a\u53d7\u8bd5\u5316\u5408\u7269\u4e2d\u67098\u4e2a\u5728\u7334\u4f53\u5185\u7684\u751f\u7269\u5229\u7528\u5ea6\u663e\u8457\u4f4e\u4e8e\u4eba\u4f53\uff0c\u56e0\u4e3a\u7334\u7684\u80a0\u9053\u4ee3\u8c22\u66f4\u5f3a\u3002\u7ed3\u8bba\uff1a\u52a8\u7269\u6a21\u578b\u53ef\u4ee5\u4f30\u8ba1\u201c\u5438\u6536\u201d\uff0c\u4f46\u201c\u5438\u6536\u00d7\u9996\u8fc7\u4ee3\u8c22\u201d\u7684\u4e58\u79ef\uff0c\u522b\u6307\u671b\u52a8\u7269\u3002<\/p>\n\n\n\n<h6 class=\"wp-block-heading\"><strong>\u8ba1\u7b97\u673a\u6a21\u578b<\/strong><\/h6>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>QSBR\u6a21\u578b\uff08Andrews\u7b49\uff09<\/strong><strong>\uff1a<\/strong>591\u4e2a\u836f\u7269\u00d782\u4e2a\u5b50\u7ed3\u6784\u63cf\u8ff0\u7b26\u7684\u9010\u6b65\u56de\u5f52\uff0c\u9884\u6d4b\u4eba\u53e3\u670d\u751f\u7269\u5229\u7528\u5ea6\u4f18\u4e8eLipinski\u7c7b\u836f\u4e94\u89c4\u5219\uff08\u6700\u65e9\u7684\u53e3\u670d\u5438\u6536\u5b9a\u6027\u6a21\u578b\uff09\uff0c\u4e14\u80fd\u6307\u51fa\u5f71\u54cdF\u7684\u5173\u952e\u5b50\u7ed3\u6784\u3001\u53cd\u54fa\u836f\u7269\u8bbe\u8ba1\uff1bYoshida\u7b49\u7684\u6709\u5e8f\u591a\u5206\u7c7bQSAR\u5728232\u4e2a\u836f\u7269\u4e0a\u6b63\u786e\u738771%\uff0c\u5bf940\u4e2a\u5916\u90e8\u836f\u7269\u9884\u6d4b\u51c6\u786e\u738760%\uff1b<\/li>\n\n\n\n<li><strong>PBPK\u6a21\u578b\uff1a<\/strong>\u4ece\u5f25\u6563\u6a21\u578b\u3001\u623f\u5ba4\u6a21\u578b\u5438\u6536\u4e0e\u8f6c\u8fd0\uff08CAT\uff09\u5230\u9ad8\u7ea7\u623f\u5ba4\u5438\u6536\u4e0e\u8f6c\u8fd0\uff08ACAT\uff09\u6a21\u578b\uff089\u4e2a\u80c3\u80a0\u8282\u6bb5\u7684\u751f\u7406\u6a21\u578b\uff0c\u53ef\u63cf\u8ff0\u91ca\u653e\u3001\u6eb6\u89e3\u3001\u964d\u89e3\u3001\u4ee3\u8c22\u3001\u6444\u53d6\u3001\u5438\u6536\u5168\u8fc7\u7a0b\uff09\uff0c\u5df2\u5f62\u6210GastroPlus\u2122\u3001PKSim<sup>\u00ae<\/sup>\u3001IDEA\u2122\u3001Simcyp<sup>\u00ae<\/sup>\u7b49\u5546\u4e1a\u5316\u8f6f\u4ef6\u751f\u6001\u3002<\/li>\n<\/ul>\n\n\n\n<h5 class=\"wp-block-heading\"><strong>\u56db\u3001\u836f\u65f6\u66f2\u7ebf\u9884\u6d4b<\/strong><\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">FIH\u5242\u91cf\u8bbe\u8ba1\u771f\u6b63\u5173\u5fc3\u7684\uff0c\u662f\u7ed9\u836f\u540e\u7684AUC\u3001\u6d88\u9664\u534a\u8870\u671f\u3001\u5cf0\u8c37\u6d53\u5ea6\u6bd4\u2014\u2014\u65e2\u8981\u4fdd\u8bc1\u66b4\u9732\u91cf\u8db3\u591f\u6709\u6548\uff0c\u53c8\u8981\u9760C<sub>max<\/sub>\u548cC<sub>min<\/sub>\u7684\u9884\u5224\u6765\u89c4\u907f\u6bd2\u6027\u3001\u7ef4\u6301\u6709\u6548\u6d53\u5ea6\u3002\u603b\u7ed3\u4e3a\u4e09\u79cd\u66f2\u7ebf\u7ea7\u9884\u6d4b\u5de5\u5177\uff1a<\/p>\n\n\n\n<h6 class=\"wp-block-heading\"><strong>\u2460 \u79cd\u5c5e\u4e0d\u53d8\u65f6\u95f4\u6cd5\uff08Dedrick\u56fe\uff09<\/strong><\/h6>\n\n\n\n<p class=\"wp-block-paragraph\">\u6e90\u4e8e\u5f02\u901f\u653e\u5927\u601d\u60f3\uff1a\u628a\u6d53\u5ea6\u8f74\u6309\u5242\u91cf\u6216\u4f53\u91cd\u5f52\u4e00\u3001\u628a\u5b9e\u9645\u65f6\u95f4\u53d8\u6362\u4e3a\u751f\u7406\u65f6\u95f4\uff08\u4ee5\u5fc3\u8df3\u6570\/\u547c\u5438\u6570\u5b9a\u4e49\uff09\uff0c\u4e0d\u540c\u79cd\u5c5e\u7684\u8840\u836f\u6d53\u5ea6\u66f2\u7ebf\u7406\u8bba\u4e0a\u53ef\u4ee5\u53e0\u52a0\uff0c\u518d\u53cd\u53d8\u6362\u56de\u4eba\u4f53\u3002<\/p>\n\n\n\n<h6 class=\"wp-block-heading\"><strong>\u2461 C<\/strong><sub><strong>ss<\/strong><\/sub><strong>\u2013MRT\u6cd5<\/strong><\/h6>\n\n\n\n<p class=\"wp-block-paragraph\">Wajima\u7b49\u63d0\u51fa\uff1a\u5c06\u65f6\u95f4\u8f74\u9664\u4ee5\u5e73\u5747\u6ede\u7559\u65f6\u95f4\uff08MRT\uff09\u3001\u6d53\u5ea6\u8f74\u9664\u4ee5\u7a33\u6001\u6d53\u5ea6\uff08C<sub>ss<\/sub> = \u5242\u91cf\/V<sub>d,ss<\/sub>\uff09\uff0c\u5404\u52a8\u7269\u79cd\u5c5e\u7684\u836f\u65f6\u66f2\u7ebf\u53ef\u4ee5\u826f\u597d\u53e0\u52a0\u2014\u2014\u8fd9\u89c4\u907f\u4e86Dedrick\u56fe\u4e2d\u66f2\u7ebf\u53e0\u52a0\u4e0d\u4f73\u7684\u95ee\u9898\u3002\u518d\u7528\u9884\u6d4b\u7684\u4eba\u4f53C<sub>ss<\/sub>\u4e0eMRT\u53cd\u53d8\u6362\uff0c\u5373\u5f97\u4eba\u4f53\u9759\u8109\u66f2\u7ebf\uff1b\u7ed3\u5408\u5438\u6536\u901f\u7387\u5e38\u6570\u4e0e\u751f\u7269\u5229\u7528\u5ea6\u53ef\u8fdb\u4e00\u6b65\u6a21\u62df\u53e3\u670d\u66f2\u7ebf\u3002<\/p>\n\n\n\n<h6 class=\"wp-block-heading\"><strong>\u2462 PBPK\u6a21\u578b<\/strong><\/h6>\n\n\n\n<p class=\"wp-block-paragraph\">PBPK\u6a21\u578b\u5c06\u4eba\u4f53\u62c6\u5206\u4e3a\u80ba\u3001\u813e\u3001\u809d\u3001\u80a0\u3001\u8102\u80aa\u3001\u808c\u8089\u3001\u5fc3\u3001\u8111\u3001\u80be\u3001\u76ae\u80a4\u3001\u7ea2\/\u9ec4\u9aa8\u9ad3\u7b49\u591a\u4e2a\u7ec4\u7ec7\u5ba4\uff0c\u4ee5\u8840\u6db2\u5faa\u73af\u4e32\u8054\uff0c\u5047\u8bbe\u836f\u7269\u5728\u5404\u5ba4\u5185\u77ac\u95f4\u5747\u5300\u5206\u5e03\u3001\u6444\u53d6\u53d7\u8840\u6d41\/\u6269\u6563\u9650\u5236\u3002\u7ec4\u7ec7-\u8840\u6d46\u5206\u914d\u7cfb\u6570K<sub>p<\/sub>\u53ef\u7528\u7ec4\u7ec7\u7ec4\u6210\u6a21\u578b\uff08Poulin\u2013Theil\u3001Berezhkovskiy\u3001Rodgers\u7b49\u65b9\u7a0b\uff09\u9884\u6d4b\uff1bCL<sub>H<\/sub>\u7531IVIVE\u6216\u5f02\u901f\u653e\u5927\u800c\u6765\uff0cCL<sub>R<\/sub>\u7531\u5f02\u901f\u653e\u5927\u6216GFR\u6bd4\u503c\u6cd5\u4f30\u8ba1\uff1b\u53e3\u670d\u5438\u6536\u7528GastroPlus\u2122\uff08ACAT\u6a21\u578b\uff09\u7b49\u8f6f\u4ef6\u6a21\u62df\u3002<\/p>\n\n\n\n<h5 class=\"wp-block-heading\"><strong>\u4e94\u3001<\/strong><strong>\u7ed3\u8bed<\/strong><\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">\u56de\u5230\u6700\u521d\u7684\u95ee\u9898\uff1a\u7b2c\u4e00\u6b21\u4eba\u4f53\u7ed9\u836f\u7684\u5242\u91cf\u600e\u4e48\u5b9a\uff1f\u2014\u2014\u6ca1\u6709\u4efb\u4f55\u4e00\u79cd\u65b9\u6cd5\u80fd\u5728\u6240\u6709\u573a\u666f\u4e0b\u80dc\u51fa\uff0c\u5242\u91cf\u4f30\u7b97\u7684\u6bcf\u4e00\u6b21\u8fdb\u6b65\uff0c\u90fd\u6765\u81ea\u751f\u7406\u673a\u5236\u7684\u66f4\u6df1\u7406\u89e3\u4e0e\u591a\u6e90\u8bc1\u636e\u7684\u66f4\u4e25\u6574\u5408\uff0c\u800c\u4e0d\u662f\u67d0\u4e00\u4e2a\u6f02\u4eae\u516c\u5f0f\u7684\u6a2a\u7a7a\u51fa\u4e16\u3002\u5bf9\u4ece\u4e1a\u8005\u7684\u542f\u793a\u6216\u8bb8\u6b63\u662f\u5982\u6b64\uff1a\u628a\u6bcf\u4e00\u4e2a\u9884\u6d4b\u90fd\u5f53\u4f5c\u5047\u8bbe\uff0c\u628a\u6bcf\u4e00\u9488\u8d77\u59cb\u5242\u91cf\u90fd\u5f53\u4f5c\u9700\u8981\u5168\u6570\u636e\u94fe\u8fa9\u62a4\u7684\u51b3\u7b56\u3002<\/p>\n\n\n\n<h5 class=\"wp-block-heading\"><strong>\u53c2\u8003\u6587\u732e<\/strong><\/h5>\n\n\n\n<ol class=\"wp-block-list\">\n<li>Zou P, Yu Y, Zheng N, Yang Y, Paholak HJ, Yu LX, Sun D. Applications of Human Pharmacokinetic Prediction in First-in-Human Dose Estimation. The AAPS Journal, 2012, 14(2): 262\u2013281.<\/li>\n\n\n\n<li>\u56fd\u5bb6\u98df\u54c1\u836f\u54c1\u76d1\u7763\u7ba1\u7406\u5c40\u836f\u54c1\u5ba1\u8bc4\u4e2d\u5fc3\u3002\u5065\u5eb7\u6210\u5e74\u5fd7\u613f\u8005\u9996\u6b21\u4e34\u5e8a\u8bd5\u9a8c\u836f\u7269\u6700\u5927\u63a8\u8350\u8d77\u59cb\u5242\u91cf\u7684\u4f30\u7b97\u6307\u5bfc\u539f\u5219 [S]. \u5317\u4eac\uff1a\u56fd\u5bb6\u98df\u54c1\u836f\u54c1\u76d1\u7763\u7ba1\u7406\u5c40\uff0c2012.<\/li>\n<\/ol>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u64b0\u6587\uff1a\u8042\u8339\u4f73 \u79e6\u96e8<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u5ba1\u6838\uff1a\u5bab\u96ea<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n","protected":false},"excerpt":{"rendered":"<p>2006\u5e743\u670813\u65e5\uff0c\u4f26\u6566\u3002\u4e00\u5bb6\u533b\u9662\u91cc\uff0c8\u540d\u5065\u5eb7\u7684\u5e74\u8f7b\u5fd7\u613f\u8005\u53c2\u52a0\u4e86\u4ee3\u53f7TGN1412\uff08\u6297CD28\u5355\u514b\u9686\u6297\u4f53\uff09\u7684\u4e00\u671f\u4e34\u5e8a\u8bd5\u9a8c\u3002\u7ed9\u836f\u540e\u77ed\u77ed\u6570\u5c0f\u65f6\u5185\uff0c6\u4eba\u53d1\u751f\u5267\u70c8\u7684\u7ec6\u80de\u56e0\u5b50\u98ce\u66b4\u4e0e\u591a\u5668\u5b98\u8870\u7aed\uff0c\u88ab\u9001\u8fdb\u91cd\u75c7\u76d1\u62a4\u5ba4\u2014\u2014\u8fd9\u5c31\u662f\u65b0\u836f\u53f2\u4e0a\u8457\u540d\u7684\u201c\u5927\u8c61\u4eba\u8bd5\u9a8c\u201d\u4e8b\u4ef6\u3002<br \/>\n\u503c\u5f97\u6df1\u601d\u7684\u662f\uff1a\u8fd9\u4e2a\u5242\u91cf\u5e76\u975e\u8349\u7387\u62cd\u677f\u3002\u8bd5\u9a8c\u524d\uff0c\u7533\u529e\u65b9\u4f9d\u636e\u98df\u87f9\u7334\u7684NOAEL\uff08\u672a\u89c2\u5bdf\u5230\u6709\u5bb3\u4f5c\u7528\u5242\u91cf\uff0950 mg\/kg\uff0c\u6309\u4f53\u91cd\u6362\u7b97\u51fa\u4eba\u4f53\u7b49\u6548\u5242\u91cf16 mg\/kg\uff0c\u53c8\u53e0\u52a0\u4e86\u9ad8\u8fbe160\u500d\u7684\u5b89\u5168\u7cfb\u6570\uff0c\u6700\u7ec8\u7ed9\u51fa0.1 mg\/kg\u7684\u8d77\u59cb\u5242\u91cf\u2014\u2014\u7ed3\u679c\u5728\u4eba\u4f53\u5185\u4ecd\u9020\u6210\u4e86\u8d85\u8fc790%\u7684\u53d7\u4f53\u5360\u7528\uff0c\u8db3\u4ee5\u5f15\u53d1\u707e\u96be\u6027\u4e0d\u826f\u53cd\u5e94\u3002\u800c\u5982\u679c\u7528\u540e\u6765\u6b27\u6d32\u63a8\u884c\u7684MABEL\u65b9\u6cd5\u4f30\u7b97\uff0c\u5b89\u5168\u8d77\u59cb\u5242\u91cf\u5e94\u4e3a0.001 mg\/kg\uff0c\u4ec5\u4e3a\u5b9e\u9645\u7ed9\u836f\u91cf\u7684\u767e\u5206\u4e4b\u4e00\u3002<br \/>\n\u8fd9\u573a\u60b2\u5267\u628a\u4e00\u4e2a\u95ee\u9898\u63a8\u5230\u4e86\u6240\u6709\u836f\u7269\u7814\u53d1\u8005\u9762\u524d\uff1a\u7b2c\u4e00\u6b21\u628a\u4e00\u4e2a\u65b0\u5206\u5b50\u653e\u8fdb\u4eba\u4f53\uff0c\u7b2c\u4e00\u9488\u5230\u5e95\u8be5\u6253\u591a\u5c11\uff1f<br \/>\n\u672c\u6587\u57fa\u4e8e\u7ecf\u5178\u7efc\u8ff0\uff08Zou et al., AAPS J, 2012\uff09[1]\u53ca\u76f8\u5173\u6307\u5bfc\u539f\u5219\uff0c\u7cfb\u7edf\u68b3\u7406FIH\u5242\u91cf\u4f30\u7b97\u7684\u65b9\u6cd5\u5b66\u5168\u666f\uff1a5\u79cd\u5242\u91cf\u4f30\u7b97\u65b9\u6cd5\u300117\u79cd\u4eba\u4f53\u6e05\u9664\u7387\u9884\u6d4b\u65b9\u6cd5\u30016\u79cd\u751f\u7269\u5229\u7528\u5ea6\u9884\u6d4b\u65b9\u6cd5\u30013\u79cd\u836f\u65f6\u66f2\u7ebf\u9884\u6d4b\u5de5\u5177\u2014\u2014\u4ee5\u53ca\u5b83\u4eec\u7684\u51c6\u786e\u6027\u8fb9\u754c\u3002<\/p>\n","protected":false},"author":1,"featured_media":2298,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[147],"tags":[44,35,86,15,32,34,29],"class_list":["post-2297","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-147","tag-44","tag-35","tag-86","tag-15","tag-32","tag-34","tag-29"],"_links":{"self":[{"href":"https:\/\/www.millibuff.com\/index.php?rest_route=\/wp\/v2\/posts\/2297","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.millibuff.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.millibuff.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.millibuff.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.millibuff.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2297"}],"version-history":[{"count":3,"href":"https:\/\/www.millibuff.com\/index.php?rest_route=\/wp\/v2\/posts\/2297\/revisions"}],"predecessor-version":[{"id":2302,"href":"https:\/\/www.millibuff.com\/index.php?rest_route=\/wp\/v2\/posts\/2297\/revisions\/2302"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.millibuff.com\/index.php?rest_route=\/wp\/v2\/media\/2298"}],"wp:attachment":[{"href":"https:\/\/www.millibuff.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2297"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.millibuff.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2297"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.millibuff.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2297"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}