羧胺三唑胶丸I期临床研究  

Phase I clinical trial of a gelcap formulation of carboxyamidotriazole

作　　者：杨林[1] 王金万[1] 李全胜[2] 刘昌孝[2] 叶菜英[3] 杜春霞[1] 李树婷[1] 张和平[1] 董英[1] 张德昌[3] 

机构地区：[1]中国医学科学院肿瘤医院内科,北京100021 [2]天津药物研究院药代与临床药理研究室,天津300193 [3]中国医学科学院基础医学研究所药理室,北京100021

出　　处：《中国新药杂志》2008年第22期1972-1976,1979,共6页Chinese Journal of New Drugs

摘　　要：目的：在晚期恶性肿瘤患者中观察羧胺三唑（CAI）胶丸的安全性、耐受性和药动学特点,确定最大耐受剂量（MTD）,为Ⅱ期临床研究确定合适的剂量。方法：本研究分为单次给药（n=12）和连续给药（n=18）试验两部分。进行了50,100,150和200 mg 4个剂量组的评估。单次给药者口服1次不同剂量的CAI胶丸后进行药动学研究;连续给药患者每天1次口服羧胺三唑胶丸,连续服用28 d为1周期,观察药物的耐受性,并进行连续给药药动学研究。结果：共20例晚期恶性肿瘤患者入选。恶心、呕吐是最常见的不良反应,单次给药后4/12例患者发生了呕吐,与剂量关系不大。连续给药后11/18例发生了呕吐,与剂量相关。150 mg组7例患者中2例出现了剂量限制性毒性（DLT）。轻到中度疲乏也较常见（11/18例）。口服给药后血药浓度达峰时间约为2 h,平均清除半衰期为35-61 h,个体间血浆稳态谷浓度水平差别较大。结论：晚期恶性肿瘤患者对CA I胶丸的耐受性较好,MTD为100 mg·d^-1,恶心、呕吐和疲乏为最常见的不良反应。Objective： To investigate the tolerability and pharmacokinetic characteristics of carboxy- amidotriazole （CAI） gelatin capsule （geleap） in patients with advanced malignant tumors, and to determine the maximal tolerated dose （MTD） and recommend the appropriate dosage for phase II trial. Methods： This trial was divided into two parts, namely single dose（n = 12） and continuous doses（n = 18）. Single test dose was administered to determine the pharmacokinetic characteristics; continuous doses （once-daily CAI given in cycles of 28 days） to determine the tolerability. Results： Totally 20 patients were entered, and respectively took 50,100,150 and 200 mg. The most common adverse effects were nausea and vomiting. After single test dose, 4 of 12 patients experienced vomiting which was not related to the dose level. After continuous daily doses, 11 of 18 patients experienced vomiting that seemed to be related to the dose level; 2 of 7 patients taking 150 mg experienced dose limiting toxicity（DLT）. Mild and moderate degree of fatigue was another frequent complaint （11/18）. Peak plasma con- centration appeared at about 2 h after administration of the oral gelcap dose. The mean plasma half-life time was 35 to 61 h. Steady-state trough plasma concentrations varied among individual patients. Conclusion： The gelcap formulation of CAI is well tolerated in advanced cancer patients. The MTD is 100 mg·d^-1. Nausea and vomiting are the most frequent adverse effects.

关 键 词：羧胺三唑 最大耐受剂量 剂量限制性毒性 药动学 耐受性 

分 类 号：R730.5[医药卫生—肿瘤] R979.1[医药卫生—临床医学]