含柚皮甘中藥對Cyclostorin之藥品動力學影響

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题名:	含柚皮甘中藥對Cyclostorin之藥品動力學影響 The Influence of Naringin-Containing Chinese Herbs on Cyclosporin Pharmacokinetics
作者:	李珮端;徐素蘭
贡献者:	中國醫藥學院藥學系
关键词:	柚皮？;環孢靈;中草藥;藥物動力學;葡萄柚汁;藥物交互作用;柚皮？元;柚皮芸香？;Naringin;Cyclosporin;Chinese herbal medicine;Pharmacokinetics;Grapefruit juice;Drug interaction;Naringenin;Narirutin
日期:	1999-06
上传时间:	2010-09-06 23:33:29 (UTC+8)
摘要:	枳殼、化州橘紅與葡萄柚之基原同為柑橘屬植物,柚皮？為其共同之主要成分且其他化學成分組成亦頗類似,因此葡萄柚汁與抗排斥藥環孢靈(Cyclosporin)所產生之交互作用,亦極有可能在此兩種中藥與環孢靈併用時發生。本研究以豬為模型,探討枳殼、化州橘紅對環孢靈動力學之影響。血中環孢靈濃度之定量,係採用臨床使用之螢光偏極免疫法 (Fluorescence polarization immuno assay, FPIA),結果顯示此兩種中藥水煎劑均會造成環孢靈之血峰濃度(C/sub max/)增高,化州橘紅水煎劑亦使環孢靈血藥曲線下面積(AUC/sub 0-t/)顯著提高了95%,兩種水煎劑並可造成環孢靈之急性毒性反應,如震顫、胃腸脹氣、厭食及倦怠等。因此環孢靈與此兩種中藥併用時,其安全性堪慮, 此現象值得臨床醫療人員與病患注意。柚皮？(Naringin)、柚皮？元(Naringenin)及柚皮芸香？(Narirutin)是常用中藥枳殼、枳實、化州橘紅及柚子、葡萄柚之活性成分。柚皮？具抗胃潰瘍、抗炎止痛、抗氧化與抗癌之作用。而柚皮？與柚皮芸香？之代謝物柚皮？元則具抗氧化、抗胃潰瘍、抑制乳房腫瘤細胞增生及延緩發生與抑制CYP1A2及3A4等藥理作用。本研究開發以HPLC定量枳殼、化州橘紅藥材水煎劑中柚皮？、柚皮芸香？與柚皮？元含量之方法,其精確度良好,可供中藥品管之應用。另外從本研究之定量結果中亦發現,柚皮？等成分之含量多寡與環孢靈血藥曲線下面積之增加程度並無相關,故柚皮？與柚皮？元應非造成上述血藥濃度增加之主因,而真正之肇因成分則值得針對枳殼、化州橘紅與葡萄柚之其他共同成分進一步研究探索。 The origins of zhiqiao and huajuhong are Citrus fruits as grapefruit. They contain the same major constituent-naringin and their many other constituents are quite similar. Because the interaction of grapefruit juice on cyclosporin absorption has been documented, this prompted us to investigated the interactions of these Citrus decoctions with cyclosporin in swines. FPIA method (Fluorescence Polarization Immuno Assay) was employed to determine the blood cyclosporin concentrations. The results showed these two decoctions raised the peak blood concentration of cyclosporin (C/sub max/). The decoction of huajuhong significantly increased the AUC/sub 0-t/ of cyclosporin by 95%. Acute intoxication of cyclosporin was observed when the decoction of zhiqiao or huajuhong was coadministered. It is suggested that blood cyclosporin concentration should be carefully monitored when cyclosporin was coadministered with these two Citrus herbal decoctions. Naringin, narirutin and naringenin are active constituents in zhiqiao, huajuhong and grapefruit juice. The contents of these dihydroflavones in these Citrus herbal decoctions and grapefruit juice were determined by an HPLC method developed in our laboratory. This assay method could be applicable to quality control of Chinese medicinal products. In addition, our results indicated there was no correlation between the ingested dose of naringin and the extent of AUC increase. Therefore, naringin and naringenin should not be the causative agents for the interaction. It is worthy to further investigate the other common constituents among zhiqiao, huajuhong and grapefruit juice to find out the major causative compound which is responsible for the interaction with cyclosporin.
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