常用中西藥同時併用之交互作用風險評估

胡幼圃
國防醫學院
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。
計畫主持人94~95年在中醫藥委員會的資助下進行了「已上市中藥對體內肝臟酵素活性之影響研究」，此研究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，結果發現1.挑選了30種常用濃縮中藥來做測試，結果即發現至少有一半以上會對人體肝臟代謝酵素有顯著的影響，比例非常高，其中蒼耳散抑制CYP1A2之活性達99.2 ± 1.4%; 正骨紫金丹抑制CYP2D6活性達85.4 ± 7.7%; 甘露飲抑制CYP2C9活性達82.2 ± 8.7%; 正骨紫金丹抑制CYP3A4活性達89.6 ± 6.1%; 清心蓮子飲抑制UGT2B7活性達92.8 ± 1.8%。2.龍膽瀉肝湯經人類肝微粒體體外試驗及大白鼠體內藥動試驗、病理切片觀察，發現在併服nalbuphine後會對大白鼠肝有所損傷HAI score顯著上升(1.6 ± 0.89上升至 4.40 ± 2.07)，代謝酵素活性也顯著下降，nalbuphine在體內的吸收量(AUCtotal)大幅增加25至40倍，體內最高濃度(Cmax)也大幅升高12至15倍，排除半衰期也增長3至6倍，已明顯產生藥物-藥物交互作用。
關鍵字：中西藥併用；中西藥交互作用；CYP450; UGT

Risk Evaluation of Herb-Drug Interaction

Oliver Yoa-Pu Hu
National Defense Medical Center
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.
關鍵字：Drug-drug interaction, Herb-drug interaction, CYP450, UGT