Thalidomide 在1950 年代的時候被使用於鎮靜安眠的藥物，以及用於孕婦在懷孕時期改善噁心及嘔吐的症狀。但是到了1960 年時，因為會對孕婦造成畸胎及神經毒性的形成而禁用。最近幾年，許多的研究學者調查發現到，thalidomide 在生物上的影響包含了免疫調節作用，以及經由抑制tumor necrosis factor (TNF-a)這個生長因子來抑制血管新生作用。因此現在這個藥物被重新拿來作為許多惡性疾病的相關研究，包括erythem nodosum leprosum (ENL)、黑色素瘤、卡波西肉瘤、多發性骨隨瘤，以及其他種類的癌症疾病，並且thalidomide 在許多的臨床試驗中展現出相當顯著的治療效果。而從兔子及老鼠眼睛的實驗中，已經知道thalidomide是屬於抗血管新生作用的藥物，但是在雞胚胎絨毛膜試驗(Chicken chorioallantoic membrane assays，CAM)中卻無法看到這樣的結果。這是否意味著thalidomide 是需要經由代謝才能產生作用的前驅藥物？然而thalidomide 的作用機轉到目前為止並不是非常的清楚。所以在藥物動態學方面，從臨床試驗中分析肝癌病人的血液，我們可以定量thalidomide的血中濃度。但從病人血液中分析thalidomide 的主要代謝產物5-hydroxythalidomide，則因為濃度太低而無法測得。在尿液分析上5-hydroxythalidomide 的濃度則約為thalidomide 濃度的10%。
　　我們為了要了解到thalidomide 是否為形成活性藥物的前驅藥物而展現出抑制血管新生的作用，所以進行雞胚胎絨毛膜試驗(Chicken chorioallantoic membrane assays，CAM)。在單純的處理thalidomide 時，確實沒看到抑制血管生長的情形； 而在處理其主要代謝產物5-hydroxythalidomide 時，隨著劑量的增加但是都沒有產生抑制血管生長的情形。利用人類肝臟微粒體先將thalidomide 進行代謝而萃取出的產物作試驗，隨著萃取產物處理劑量的增加，也都沒發現到有抑制血管新生的情形。因此，我們結論，5-hydroxythalidomide 並不是thalidomide 產生抗血管新生作用活性代謝物，而thalidomide 產生抗血管新生的作用，有可能是其在代謝的過程中產生的其他的中間活性代謝產物所產生的結果。

　　Thalidomide was introduced as an oral sedative-hypotic drug and used to ameliorate nausea and vomiting during pregnancy in the late 1950s. But in 1960, it was forbidden because of its teratogenicity and neuropathy to the pregnant mothers. Recently, the investigators discovered that the biological effects of thalidomide include immunomodulation and the inhibition of angiogenesis about the suppression of tumor necrosis factor alpha (TNF-a). It has now returned to practices as an effective oral agent in the management of various disease states including erythem nodosum leprosum (ENL), melanoma, Kaposi’s sarcoma, multiple myeloma and other kinds of cancer. Thalidomide expressed its remarkably therapeutic effects in the clinical trails of thease disease. It was known that thalidomide is an antiangiogenetic drug in the rabbit and mouse corneal assay, but the same result can’t be observed in the CAM (Chicken chorioallantoic membrane) assay. It suggested that thalidomide might be a prodrug to show the antiangiogenesis. However, the thalidomide’s mechanism of action remains unknown. From the analysis of the blood concentrations of hepatoma patients in the clinical trail, we detected thalidomide, but not its major metabolite, 5-hydroxythalidomide. From the urine, the concentration is about the 10% of the thalidomide. On the CAM study, we try to figure out whether thalidomide is a prodrug to form the active drug to induce antiangiogenesis. In the CAM assay, we couldn’t find the antiangiogenesis of the thalidomide. We also found that with the increasing dose, the major metabolite 5-hydroxythalidomide has no effect on the antiangiogenesis. We incubated the human microsome and the thalidomide. After treating the extracted products with the increasing amount, we couldn’t find the antiangiogenic effect on the CAM assay either. We therefore concluded that the 5-hydroxythalidomide is not the active metabolite of thalidomide. Thalidomide might be metabolized to form the other intermediate metabolite to exert the antiangiogenesis.

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