{"id":304,"date":"2018-12-04T10:46:18","date_gmt":"2018-12-04T02:46:18","guid":{"rendered":"http:\/\/www.jsxtsw.com\/?p=304"},"modified":"2021-12-03T15:45:49","modified_gmt":"2021-12-03T07:45:49","slug":"%e7%94%98%e8%8d%89%e9%85%b8%e5%be%88%e6%9c%89%e5%8f%af%e8%83%bd%e6%88%90%e4%b8%ba%e8%82%9d%e8%84%8foatp1b1-1b3%e8%bd%ac%e8%bf%90%e4%bd%93%e4%bb%8b%e5%af%bc%e7%9a%84%e8%8d%af%e7%89%a9%e7%9b%b8%e4%ba%92","status":"publish","type":"post","link":"http:\/\/www.jsxtsw.com\/en\/304\/","title":{"rendered":"\u7518\u8349\u9178\u5f88\u6709\u53ef\u80fd\u6210\u4e3a\u809d\u810fOATP1B1\/1B3\u8f6c\u8fd0\u4f53\u4ecb\u5bfc\u7684\u836f\u7269\u76f8\u4e92\u4f5c\u7528\u7684\u201c\u53d7\u5bb3\u8005\u201d"},"content":{"rendered":"<section class=\"\">\n<section>\n<section><strong>\u6765\u6e90\uff1aBr J Pharmacol. 2018 Jun 16.<\/strong><\/section>\n<\/section>\n<\/section>\n<section class=\"\">\n<section>\n<section>\n<section><strong>\u539f\u6587\u4f5c\u8005<\/strong><\/section>\n<section>\n<section><\/section>\n<section><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<section class=\"\">\n<section>\n<section>Jiajia Dong<sup>1,2<\/sup>,Olajide E.Olaleye<sup>1<\/sup>, Rongrong Jiang<sup>1<\/sup>, Jing Li<sup>1<\/sup>,Chuang Lu<sup>3<\/sup>, Feifei Du<sup>1<\/sup>,Fang Xu<sup>1<\/sup>,Junling Yang<sup>1<\/sup>, Fengqing Wang<sup>1<\/sup>,Weiwei Jia<sup>1<\/sup>,Chuan Li<sup>1,2<\/sup><\/section>\n<\/section>\n<\/section>\n<p><sup>1<\/sup>\u4e2d\u56fd\u79d1\u5b66\u9662\u4e0a\u6d77\u836f\u7269\u7814\u7a76\u6240<\/p>\n<p><sup>2<\/sup>\u4e2d\u79d1\u9662<\/p>\n<p><sup>3<\/sup>\u8d5b\u8bfa\u83f2\u516c\u53f8\uff0c\u7f8e\u56fdDMPK\u90e8\u95e8<\/p>\n<section class=\"\">\n<section>\n<section>\n<section><strong>\u7ffb\u8bd1<\/strong><\/section>\n<section>\n<section><\/section>\n<section><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<section class=\"\">\n<section>\n<section>\u4f55\u7ea2\u6885\u00a0 \u51e1\u9ed8\u8c37\u6280\u672f\u90e8<\/section>\n<\/section>\n<\/section>\n<section class=\"\">\n<section>\n<section>\n<section><strong>\u5173\u952e\u8bcd<\/strong><\/section>\n<section>\n<section><\/section>\n<section><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<section class=\"\">\n<section>\n<section>\u4fdd\u809d\u7518\u8349\u9178\u8f6c\u8fd0\u4f53\u80c6\u6c41\u6392\u6cc4<\/p>\n<p>\u836f\u7269\u76f8\u4e92\u4f5c\u7528<\/p>\n<\/section>\n<\/section>\n<\/section>\n<section class=\"\">\n<section>\n<section>\n<section><strong>\u6458\u8981<\/strong><\/section>\n<section>\n<section><\/section>\n<section><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<section class=\"\">\n<section>\n<section><strong>\u7814\u7a76\u80cc\u666f\u4e0e\u76ee\u7684\uff1a<\/strong>\u9759\u8109\u6ce8\u5c04\u7518\u8349\u751c\u7d20\uff0c\u5177\u6709\u6297\u708e\u548c\u4fdd\u809d\u7684\u4f5c\u7528\uff1b\u7528\u4e8e\u809d\u75c5\u7684\u4e34\u5e8a\u6cbb\u7597\uff0c\u7ecf\u5e38\u4e0e\u5176\u4ed6\u836f\u7269\u8054\u5408\u4f7f\u7528\u3002\u672c\u6b21\u7814\u7a76\u65e8\u5728\u9610\u660e\u7518\u8349\u751c\u7d20\u809d\u80c6\u6392\u6cc4\u7684\u5206\u5b50\u673a\u5236\uff0c\u5e76\u7814\u7a76\u56e0\u6709\u673a\u9634\u79bb\u5b50\u8f6c\u8fd0\u4f53OATP1B\u4ecb\u5bfc\u5f15\u8d77\u7684\u6f5c\u5728\u836f\u7269\u76f8\u4e92\u4f5c\u7528DDI\u5bf9\u7518\u8349\u751c\u7d20\u7684\u5f71\u54cd\u3002<strong>\u5b9e\u9a8c\u65b9\u6cd5\uff1a<\/strong>\u5728\u7ec6\u80de\u548c\u56ca\u6ce1\u6c34\u5e73\u4e0a\u8868\u5f81\u809d\u8f6c\u8fd0\u86cb\u767d\uff0c\u5e76\u4e0e\u5927\u9f20\u8f6c\u8fd0\u4f53\u8fdb\u884c\u6bd4\u8f83\uff0c\u91c7\u7528\u5927\u9f20\uff08\u5927\u9f20\u4e3aOATP1B2\uff09\u7684\u5229\u798f\u5e73\uff08OATP1B\u6291\u5236\u5242\uff09\u6291\u5236\u5b9e\u9a8c\u8bc4\u4f30OATP1B2\u5728\u7518\u8349\u9178\u6e05\u9664\u548c\u836f\u52a8\u5b66\u4e2d\u7684\u4f5c\u7528\uff0c\u91c7\u7528\u6574\u5408\u4e86\u8f6c\u8fd0\u4f53\u4ecb\u5bfc\u7684\u80c6\u6c41\u6392\u6cc4\u7684\u7518\u8349\u9178\u7684PBPK\u6a21\u578b\uff0c\u5e76\u7528\u8be5\u6a21\u578b\u9884\u6d4b\u4e86\u4eba\u4f53\u5185\u7518\u8349\u9178\u7684\u6f5c\u5728\u836f\u7269\u76f8\u4e92\u4f5c\u7528\u3002<\/p>\n<p><strong>\u7ed3\u679c\uff1a<\/strong><\/p>\n<p>\u4ebaOATP1B1\/1B3\u6444\u53d6\u8f6c\u8fd0\u4f53\uff08\u5bf9\u5e94\u5927\u9f20OATP1B2\uff09\u5c06\u7518\u8349\u9178\u4ece\u8840\u6db2\u6444\u53d6\u8fdb\u5165\u809d\u810f\uff0c\u4eba\u5916\u6392\u8f6c\u8fd0\u4f53MRP2\u3001BCRP\u3001BSEP\u3001MDR-1\uff08\u5bf9\u5e94\u5927\u9f20MRP2\/BCRP\/BSEP\uff09\u4ecb\u5bfc\u836f\u7269\u5916\u6392\u8fdb\u5165\u80c6\u6c41\u4e2d\u3002\u5229\u798f\u5e73\uff08OATP1B\u6291\u5236\u5242\uff09\u5c06\u6291\u5236\u5927\u9f20\u809d\u810f\u6444\u53d6\u578b\u8f6c\u8fd0\u4f53\uff0c\u5bfc\u81f4\u7518\u8349\u9178\u7684\u7cfb\u7edf\u66b4\u9732\u91cf\u660e\u663e\u589e\u52a0\uff1b\u6b64\u5916\uff0c\u7518\u8349\u9178\u4e0e\u8840\u6d46\u86cb\u767d\u5e7f\u6cdb\u7ed3\u5408\uff0c\u5176\u80be\u5c0f\u7403\u6ee4\u8fc7\u7387\u8f83\u4f4e\u3002\u6700\u7ec8\u5bfc\u81f4\u7518\u8349\u9178\u4f53\u5185\u66b4\u9732\u91cf\u8f83\u9ad8\u3002PBPK\u6a21\u578b\u7684\u5b9a\u91cf\u5206\u6790\u8868\u660e\u5f53\u7518\u8349\u9178\u4e0e\u8f6c\u8fd0\u4f53\u6291\u5236\u5242\u8054\u5408\u7ed9\u836f\u65f6\uff0c\u7518\u8349\u9178\u836f\u52a8\u5b66\u8fc7\u7a0b\u4e2d\u53d1\u6325\u5173\u952e\u4f5c\u7528\u7684OATP1B1\/1B3\u5c06\u53d7\u5230\u6291\u5236\uff0c\u5e76\u5f15\u8d77\u6f5c\u5728\u7684\u836f\u7269\u76f8\u4e92\u4f5c\u7528DDI\u98ce\u9669\u3002<\/p>\n<p><strong>\u7ed3\u8bba\uff1a<\/strong><\/p>\n<p>\u8f6c\u8fd0\u4f53\u4ecb\u5bfc\u7518\u8349\u9178\u7684\u809d\u810f\u6444\u53d6\u4e0e\u80c6\u6c41\u6392\u6cc4\uff0c\u5f71\u54cd\u5176\u6d88\u9664\u4e0e\u836f\u4ee3\u52a8\u529b\u5b66\uff0c\u5b9a\u91cf\u5206\u6790OATP1B1\/1B3\u8f6c\u8fd0\u4f53\u4ecb\u5bfc\u7684\u7518\u8349\u9178\u6f5c\u5728DDI\u98ce\u9669\uff0c\u53ef\u4ee5\u589e\u5f3a\u7518\u8349\u9178\u4e0e\u5176\u4ed6\u836f\u7269\u5408\u7528\u6cbb\u7597\u809d\u810f\u75be\u75c5\u7684\u6210\u529f\u7387\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n<section class=\"\">\n<section>\n<section>\n<section><strong>Abstract<\/strong><\/section>\n<section>\n<section><\/section>\n<section><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<section class=\"\">\n<section>\n<section><strong>BACKGROUND AND PURPOSE<\/strong>Intravenous glycyrrhizin, having anti-inflammatory and hepatoprotective properties, is incorporated intothemanagement of liver diseases in China. This investigation was designed toelucidatethemolecular mechanism underlying hepatobiliary excretion of glycyrrhizin and toinvestigateits potentialfordrug-druginteractions on organic anion-transporting polypeptides (OATP)1B.<strong>EXPERIMENTAL APPROACH<\/strong>Human hepatic transporters were characterized forglycyrrhizin at the cellular and vesicular levelsand compared with rat hepatic transporters. A rifampin-based inhibition study in rats evaluated the role of Oatp1b2in glycyrrhizin\u2019selimination andpharmacokinetics.Aphysiologically-based pharmacokinetic(PBPK)modelfor glycyrrhizin,incorporating transporter-mediated hepatobiliary excretion,was established and applied to predicting potential drug-drug interactions relating to glycyrrhizinin humans.<\/p>\n<p><strong>KEY RESULTS<\/strong><\/p>\n<p>Hepatobiliary excretion of glycyrrhizin involved human OATP1B1\/1B3-(orOatp1b2inrats)mediated hepatic uptake from blood and human multidrug resistance-associated protein (MRP)2\/breast cancer resistance protein (BCRP)\/bile salt export pump (BSEP)\/multidrug resistance protein(MDR)1-(orMrp2\/Bcrp\/Bsepin rats)mediatedhepaticefflux into bile. Impairment of hepatic uptakein rats by rifampin resulted insignificantly increased systemic exposure to glycyrrhizin, which had slow glomerular-filtration-based renal excretion due to extensive protein-binding in plasma. Quantitative analysis using the PBPK model demonstrated the critical roles of OATP1B1\/1B3 in pharmacokinetics ofglycyrrhizin,which hadhigh likelihoodto be avictimof drug-drug interactions when coadministered with potent dual inhibitors of these transporters.<\/p>\n<p><strong>CONCLUSION AND IMPLICATIONS<\/strong><\/p>\n<p>Transporter-mediated hepatobiliary excretion governs glycyrrhizin\u2019selimination and pharmacokinetics. Understanding glycyrrhizin\u2019s potential drug-drug interactions on OATP1B1\/1B3 is expected to enhance success of glycyrrhizin-including combination drug therapies of liver diseases.<\/p>\n<p><img loading=\"lazy\" class=\"size-full wp-image-305 aligncenter\" src=\"http:\/\/www.jsxtsw.com\/wp-content\/uploads\/2018\/12\/\u5fae\u4fe1\u56fe\u7247_20181204104020.png\" alt=\"\" width=\"445\" height=\"434\" srcset=\"http:\/\/www.jsxtsw.com\/en\/wp-content\/uploads\/2018\/12\/\u5fae\u4fe1\u56fe\u7247_20181204104020.png 445w, http:\/\/www.jsxtsw.com\/en\/wp-content\/uploads\/2018\/12\/\u5fae\u4fe1\u56fe\u7247_20181204104020-300x293.png 300w, http:\/\/www.jsxtsw.com\/en\/wp-content\/uploads\/2018\/12\/\u5fae\u4fe1\u56fe\u7247_20181204104020-410x400.png 410w\" sizes=\"(max-width: 445px) 100vw, 445px\" \/><\/p>\n<p><strong>\u5706\u70b9\u4ee3\u8868\u4e0d\u7528\u5229\u798f\u5e73\u5904\u7406\u7a7a\u767d\u5bf9\u7167\u7ec4\u5927\u9f20\uff0c\u6b63\u65b9\u5f62\u70b9\u4ee3\u8868\u7528\u5229\u798f\u5e73\u5904\u7406\u7684\u5927\u9f20\uff0cA\u548cB\u56fe\u4ee3\u8868\u5927\u9f20\u9759\u8109\u6ce8\u5c042.6mg\/kg \u7682\u82f7\uff0c\u8840\u6d46\u4e2d\u7518\u8349\u751c\u7d20\u548c\u7518\u8349\u9178-3-O-\u7cd6\u919b\u9178\u7684\u6d53\u5ea6-\u65f6\u95f4\u66f2\u7ebf\u53ca\u5bf9\u6570\u56fe<\/strong><\/p>\n<p><img loading=\"lazy\" class=\"size-full wp-image-306 aligncenter\" src=\"http:\/\/www.jsxtsw.com\/wp-content\/uploads\/2018\/12\/\u5fae\u4fe1\u56fe\u7247_20181204104027.png\" alt=\"\" width=\"232\" height=\"312\" srcset=\"http:\/\/www.jsxtsw.com\/en\/wp-content\/uploads\/2018\/12\/\u5fae\u4fe1\u56fe\u7247_20181204104027.png 232w, http:\/\/www.jsxtsw.com\/en\/wp-content\/uploads\/2018\/12\/\u5fae\u4fe1\u56fe\u7247_20181204104027-223x300.png 223w\" sizes=\"(max-width: 232px) 100vw, 232px\" \/><\/p>\n<p><strong>A\u548cB\u56fe\u5206\u522b\u4ee3\u8868\u4eba\u9759\u8109\u6ef4\u6ce8\u7518\u8349\u751c\u7d2040mg\uff08\u7eff\u8272\u7ebf\uff09\u300180mg\uff08\u84dd\u8272\u7ebf\uff09\u3001120mg\uff08\u7ea2\u8272\u7ebf\uff09\u540e\uff0c\u8840\u6d46\u4e2d\u7518\u8349\u751c\u7d20\u7684\u6d53\u5ea6\u65f6\u95f4\u66f2\u7ebf\u56fe\u53ca\u5bf9\u6570\u56fe<\/strong><\/p>\n<\/section>\n<p>\u4e0b\u8f7d\u8be5\u7bc7\u6587\u7ae0\u7684\u82f1\u6587\u539f\u6587\u732ePDF\u6587\u4ef6\uff1a<a class=\"download-link filetype-icon filetype-pdf\"\n   title=\"\" href=\"http:\/\/www.jsxtsw.com\/en\/download\/308\/\" rel=\"nofollow\">\n\t002.Glycyrrhizin-has-a-high-likelihood-to-be-a-victim-of-drug-drug-interactions-mediated-by-hepatic-OATP1B1_1B3.pdf\t(674 downloads)\n<\/a><\/p>\n<\/section>\n<\/section>\n","protected":false},"excerpt":{"rendered":"<p>\u6765\u6e90\uff1aBr J Pharmacol. 2018 Jun 16. \u539f\u6587\u4f5c\u8005 Jiajia Dong1,2,Olajide E.Olaleye1, Rongrong Jiang1, Jing Li1,Chuang Lu3, Feifei Du1,Fang Xu1,Junling Yang1, Fengqing Wang1,Weiwei Jia1,Chuan Li1,2 1\u4e2d\u56fd\u79d1\u5b66\u9662\u4e0a\u6d77\u836f\u7269\u7814\u7a76\u6240 2\u4e2d\u79d1\u9662 3\u8d5b\u8bfa\u83f2\u516c\u53f8\uff0c\u7f8e\u56fdDMPK\u90e8\u95e8 \u7ffb\u8bd1 \u4f55\u7ea2\u6885\u00a0 \u51e1\u9ed8\u8c37\u6280\u672f\u90e8 \u5173\u952e\u8bcd \u4fdd\u809d\u7518\u8349\u9178\u8f6c\u8fd0\u4f53\u80c6\u6c41\u6392\u6cc4 \u836f\u7269\u76f8\u4e92\u4f5c\u7528 \u6458\u8981 \u7814\u7a76\u80cc\u666f\u4e0e\u76ee\u7684\uff1a\u9759\u8109\u6ce8\u5c04\u7518\u8349\u751c\u7d20\uff0c\u5177\u6709\u6297\u708e\u548c\u4fdd\u809d\u7684\u4f5c\u7528\uff1b\u7528\u4e8e\u809d\u75c5\u7684\u4e34\u5e8a\u6cbb\u7597\uff0c\u7ecf\u5e38\u4e0e\u5176\u4ed6\u836f\u7269\u8054\u5408\u4f7f\u7528\u3002\u672c\u6b21\u7814\u7a76\u65e8\u5728\u9610\u660e\u7518\u8349\u751c\u7d20\u809d\u80c6\u6392\u6cc4\u7684\u5206\u5b50\u673a\u5236\uff0c\u5e76\u7814\u7a76\u56e0\u6709\u673a\u9634\u79bb\u5b50\u8f6c\u8fd0\u4f53OATP1B\u4ecb\u5bfc\u5f15\u8d77\u7684\u6f5c\u5728\u836f\u7269\u76f8\u4e92\u4f5c\u7528DDI\u5bf9\u7518\u8349\u751c\u7d20\u7684\u5f71\u54cd\u3002\u5b9e\u9a8c\u65b9\u6cd5\uff1a\u5728\u7ec6\u80de\u548c\u56ca\u6ce1\u6c34\u5e73\u4e0a\u8868\u5f81\u809d\u8f6c\u8fd0\u86cb\u767d\uff0c\u5e76\u4e0e\u5927\u9f20\u8f6c\u8fd0\u4f53\u8fdb\u884c\u6bd4\u8f83\uff0c\u91c7\u7528\u5927\u9f20\uff08\u5927\u9f20\u4e3aOATP1B2\uff09\u7684\u5229\u798f\u5e73\uff08OATP1B\u6291\u5236\u5242\uff09\u6291\u5236\u5b9e\u9a8c\u8bc4\u4f30OATP1B2\u5728\u7518\u8349\u9178\u6e05\u9664\u548c\u836f\u52a8\u5b66\u4e2d\u7684\u4f5c\u7528\uff0c\u91c7\u7528\u6574\u5408\u4e86\u8f6c\u8fd0\u4f53\u4ecb\u5bfc\u7684\u80c6\u6c41\u6392\u6cc4\u7684\u7518\u8349\u9178\u7684PBPK\u6a21\u578b\uff0c\u5e76\u7528\u8be5\u6a21\u578b\u9884\u6d4b\u4e86\u4eba\u4f53\u5185\u7518\u8349\u9178\u7684\u6f5c\u5728\u836f\u7269\u76f8\u4e92\u4f5c\u7528\u3002 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\u7ed3\u8bba\uff1a \u8f6c\u8fd0\u4f53\u4ecb\u5bfc\u7518\u8349\u9178\u7684\u809d\u810f\u6444\u53d6\u4e0e\u80c6\u6c41\u6392\u6cc4\uff0c\u5f71\u54cd\u5176\u6d88\u9664\u4e0e\u836f\u4ee3\u52a8\u529b\u5b66\uff0c\u5b9a\u91cf\u5206\u6790OATP1B1\/1B3\u8f6c\u8fd0\u4f53\u4ecb\u5bfc\u7684\u7518\u8349\u9178\u6f5c\u5728DDI\u98ce\u9669\uff0c\u53ef\u4ee5\u589e\u5f3a\u7518\u8349\u9178\u4e0e\u5176\u4ed6\u836f\u7269\u5408\u7528\u6cbb\u7597\u809d\u810f\u75be\u75c5\u7684\u6210\u529f\u7387\u3002 Abstract BACKGROUND AND PURPOSEIntravenous glycyrrhizin, having anti-inflammatory and hepatoprotective properties, is incorporated intothemanagement of liver diseases in 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