Etoposide及其相關化合物生物分析之研究現狀   全文下載

Current Status of Bioanalysis of Etoposide and Related Compounds(1)

Etoposide （VP16） 於1983年經美國食品藥品管理局（FDA）批准上市，為治療睪丸腫瘤，Hodgkins氏及Hodgkins氏淋巴癌，小細胞肺癌，及其他各種惡性腫瘤之最有效藥物之一。VP16及其代謝產物的生物分析方法之開發，對其臨床藥物動力學，代謝降解和作用機理之研究都具有重要意義。本文討論了VP16及其代謝產物的生物分析方法之現狀及VP16的代謝途徑和作用機理研究之最新進展。目前，採用紫外，螢光或電化學檢出法的高效液相層析（HPLC）已廣泛應用於VP16及其代謝產物的生物分析，為臨床藥物動力學提供了靈敏及可靠的檢測手段。除此之外，利用現代免疫技術而開發的放射免疫測定法及酵素標記免疫吸附測定法也已相繼成功地應用於VP16及其代謝產物的生物分析。文末並討論了筆者實驗室新近開發成功的epipodophyllotoxin之新衍生物GL331的藥理及其臨床藥物動力學之研究進展。

Etoposide (VP16 or VP16-213) which was approved by the United States FDA for testicular cancer in 1983, is one of the most effective anticancer agents in the treatment of testicular teratoma, Hodgkin's and non-Hodgkin's lymphomas, small-cell lung cancer, and a variety of other malignancies. Development of bioanalytical methods for VP16 and its metabolites is critical for pharmacokinetic and metabolic studies as well as for mechanisms of action studies. In this review, the current status of the bioanalysis of VP16 and its metabolites are discussed. Recent progress in mechanism of action and metabolism studies is also presented. A number of HPLC methods employing UV, fluorescence, or electrochemical detection are available for the bioanalysis of VP16 and its metabolites. Most of these HPLC methods are sensitive and reliable enough for determining the parent drugs and their metabolites in biological fluids. In addition to radioimmunoassay, enzyme-linked immunosorbent assay (ELISA) for VP16, which is the most sensitive assay method to date, has been developed based on modern immunoassay technology. The primary pharmacological and pharmacokinetic data of GL331, a new derivative of epipodophyllotoxin discovered and developed in author's laboratory, which has shown superior antitumor activity to that of VP16, are also discussed.