含柚皮中藥對Cyclosproin之藥品動力學影響

李珮端
中國醫藥學
近年來臨床上發現葡萄柚汁會影響多種為cytochrome 3A4所代謝的西藥之動力學，甚而發生嚴重之副作用。目前懷疑此交互作用與其獨特的主成分柚皮有關，但尚未完全證實。中藥中富含柚皮的藥材有枳殼、枳實、化橘紅等，其煎劑中柚皮之含量遠高於葡萄柚汁，這些中藥是否也會改變為cytochrome 3A4所代謝的西藥之動力學，甚至影響其安全性，值得探究。

Cyclosporin為一免疫抑制劑，廣泛使用於預防器官或骨髓移植之排斥及治療葡萄膜炎、乾癬等自體免疫疾病。口服溶液之絕對生體利用率為 20-50 %，主要為腸管及肝臟之CYP 3A4所代謝。許多研究顯示併服葡萄柚汁會明顯增高cyclosporin之血中濃度。任何增高cyclosporin血中濃度之因素會導致臨床上嚴重之副作用，諸如腎毒性、高血壓、肝毒性、神經毒性等。本計畫擬探討併服富含柚皮之中藥是否也會影響 cyclosporin 之動力學。

動物試驗擬以紐西蘭白兔進行交叉設計，一組給予cyclosporin，一組給予cyclosporin及中藥煎劑。兩組均於給完 cyclosporin 後於特定之時間由耳靜脈取血，經FPIA法定量 cyclosporin之血中濃度。利用PCNONLIN 計算 AUC並以paired Student‘s test比較兩組間AUC、Cmax及Tmax之差異。

本計畫之研究成果可瞭解富含柚皮的中藥煎劑對 cyclosporin藥品動力學之影響，以提高中、西藥併用時危險性之警覺。同時可以進一步證實柚皮是否為葡萄柚汁與cyclosporin發生交互作用之主因。

關鍵字：柚皮、環胞素、藥物交互作用、藥品動力學

The influence of Naringin-Containing Chinese Herbs on Cyclosporin Pharmacokinetics

Pei-Down Lee
China Medical College
In recent decade, many reports stated that concomitant intake of grapefruit juice altered the pharmacokinetics of a variety of drugs which were metabolized by cytochrome 3A4. It was suspected the major causative factor was naringin, however, it was still not well understood. The even higher content of naringin in several Chinese herbs than grapefruit juice make us to suspect possible pharmacokinetic interactions between naringin-containing Chinese herbs and those drugs. 

Cyclosporin is an immunosuppressive agent, widely used for the prevention of rejection after transplantation and for autoimmune diseases.The oral bioavailability of cyclosporin is 20-50 %, mainly metabolized by CYP 3A4 in gut wall or liver.. Many grapefruit juice-cyclosporin interaction studies reported that grapefruit juice significantly increased the blood concentration of cyclosporin and might resulted in serious side effects, e.g. renal toxicity, hypertention, hepatoxicity, neurotoxivity etc. This proposal i
關鍵字：naringin、cyclosporin、drug interaction、pharmacokinetic