中西藥併用之利基或風險探索（I）— 藥物併服時間之影響
李珮端
中國醫藥大學
Methotrexate (MTX) 為一重要的免疫抑制劑與抗癌藥，臨床上廣用於類風濕關節炎、牛皮癬與抗癌等，但其治療指數狹窄，是唯一使用時必需進行血中濃度監測的癌症用藥。本研究室過去在中醫藥委員會支持的一系列研究成果中顯示，MTX同時併服富含多酚的中藥，如大黃、黃芩、三黃瀉心湯與葛根芩連湯等皆顯著增加MTX的全身暴露及滯留時間，並導致大白鼠致死率提高。一般於臨床藥物諮詢時，醫療人員常教導病人於服用西藥2小時後，再服用中藥或其他藥物。而此一併服方式對MTX是否安全，亟須探討。本計畫擬以大白鼠於口服MTX後1.5小時及3.0小時分別給予大黃、黃芩、三黃瀉心湯、葛根芩連湯水煎劑，控制組大白鼠給予同體積的水。每組大白鼠定時自心臟穿刺採血，血中MTX濃度以螢光偏極免疫測定法定量，以WINNONLIN軟體之無室模型分析動力學參數，並以ANOVA統計組間差異。對於交互作用顯著的中藥，將再進行MTX併服中藥對腎功能、腎小管間質損傷的評估，以了解併服中藥時對腎臟的影響。中西藥併用時之安全性是醫療安全中很重要的一環，透過研究提供相關實證依據，將能提供臨床醫療人員正確的資訊，協助解決病患相關藥物併用諮詢之問題，建構優質的用藥安全環境。
關鍵字：大黃；黃芩；三黃瀉心湯；葛根芩連湯；交互作用
The Benefit or Risk of Concurrent Use with Chinese Herb and Western Medicine — Effect of Timimg of Dosing
Chao Lee, Pei-Dawn
China Medical University
Methotrexate (MTX) is an important immunosuppressant with narrow therapeutic index. The transport of MTX was associated with MRP 1, MRP 2, MRP 3 and MRP 4. Our previous studies supported by CCMP indicated that coadministration of polyphenol-rich herbs including Dahuang, Huangchin, Sanhuang-Sheishin Tang and Gergen-Chinlien Tang resulted in the systemic exposure and residence time of MTX, which led to increased mortality of rats. In general practice of drug information consultation, the patients are suggested to take Chinese medicine at 2 hour after the administration of western medicine. Whether this way of combined therapy is safe or not await further study. This project attempts to administer MTX and then administered Chinese herbs including Dahuang, Huangchin, Sanhuang-Sheishin Tang and Gergen-Chinlien Tang at 1.5 and 3 h after MTX dosing. The pharmacokinetic parameters of MTX will be compared with those after dosing with MTX alone. The blood samples will be collected via cardiopuncture and the concentrations of MTX will be determined using FPIA method. The pharmacokinetic parameters will be calculates using noncompartment model of WINNONLIN and compared statistically using ANOVA. This study will provide useful information for the efficacy and safety of MTX in clinical use.
關鍵字：Dahuang；Huangchin；Sanhuang-Sheishin Tang；Gergen-Chinlien Tang
