CCMP95-TP-003

過去一般大眾對中藥的印象認為比起西藥較為溫和、較為安全，但是馬兜鈴酸事件卻提醒大家仍需注意中藥使用的安全性。世界各國傳統藥物引起安全性疑慮的例子在所多有，如2001年美國FDA因可能影響肝臟功能建議西門肺草(Comfrey)下架；石蠶(Germander)因引起肝傷害法、德相繼禁用；卡瓦(Kava)也有很多肝傷害案例甚至已有死亡案例故加拿大、德國、新加坡、南非及瑞士均已禁用。中藥中含有的成份會影響人體器官功能這個問題需要在短時間內釐清，以保障一般民眾用藥的安全。
影響肝功能的對象包括肝血流及肝代謝酵素，而Cytochrome P450 (CYP450)及Uridinyldiphosphate Glucuronosyl Transferase (UGT)酵素大量存在於腸胃道及肝中，近幾年來己被證實是藥物吸收產生初次代謝(first pass metabolism)的最主要的酵素之一。最近的一些研究，如despramine與fluoxetine在臨床具顯著交互作用，經研究証實，係因體內CYP450被fluoxetine抑制所致。導致藥物交互作用的原因不只是發生在不同藥物同時使用所造成，根據文獻報導某些天然物食品與藥品配服，同樣造成顯著交互作用，而追蹤其作用機轉乃因CYP450酵素受到調控使之，因此柑橘類水果或含中藥成分之食品不可配服治療藥品的理論甚囂塵上。中藥中含有影響肝臟代謝酵素活性成份，其影響肝臟代謝功能的可能性甚高，故極需評估中藥成份對肝臟各種代謝酵素活性之影響。
本計畫擬利用體外人類肝微粒體，以雞尾酒酵素活性試驗方法評估常用中藥製劑對肝臟代謝功能的影響，用來廣泛且大量對已上市的中藥進行篩檢，第一年將篩檢三家藥廠各30種常用中藥，第二年則為三家藥廠各15種常用中藥。體外篩檢的結果，進一步以大白鼠肝毒試驗、動物藥動試驗與人體臨床試驗來確認。未來中藥新藥上市前也可用以評估其安全性及藥物交互作用可能性。
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Chinese medicines are used for the thousands of years in orient. Toxicity are expected to be much mild than novel synthetic agents, but this image was broken by the reverse events caused by the aristolochic acid. And, because of causing hepatic injury, in 2001, Comfrey was suggested to withdraw from the market by the US FDA. Germander was forbidden by France and German due to its hepatic toxicity. The safety of the traditional medicines is become a public concerned issue that should be clarified as soon as possible.
The abundantly existed cytochrome P450 (CYP450) and uridinyldiphosphate glucuronosyl transferase (UGT) in intestine and liver which responsible for many drugs first-pass metabolism caused low and variable bioavailability triggers the worry that traditional medicines may significantly reduce or increase the activity of hepatic enzyme and then cause hepatic injury. These have been found in recent drug interaction studies such as despramine and fluoxetine. Up to date, how the Chinese medicines affect the hepatic enzymes dose not be researched systemically.
In this project, human liver microsomes will be used to construct the in vitro systems to test the activity of various and important hepatic enzymes in the cocktail test system. With the system, the effects of the Chinese medicines on various hepatic enzymes will be evaluated. Large scale screening should be conducted for all of the marketing Chinese medicines.
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