Kreis W, Woodcock T M, Gordon C S, Krakoff I H
Cancer Treat Rep. 1977 Oct;61(7):1347-53.
[14C]-tetrahydrouridine (THU), a strong inhibitor of cytidine (CR) deaminase, was, after iv administration, rapidly and quantitatively cleared from the blood with a plasma half-life of about 1 hour. The main pathway of excretion was through the kidneys: most of a dose of 50 mg/kg was excreted within 12 hours and excretion was essentially complete within 48 hours. Oral administration of the same dose revealed absorption of about 10% from the gastrointestinal tract. THU at 10, 25, and 50 mg/kg given 15 minutes before [3H]-cytosine arabinoside (ara-C) at a dose of 0.003 mg/kg produced about a two fold increase in ara-C blood levels at all times measured from 5 minutes to 4 hours, with only slight increases in the half-life of ara-C. A dose-related effect of THU upon the deamination of ara-C was obvious only during the time from 15 minutes to 1 hour after the injection of 3H-ara-C. The inhibitory effect of THU upon CR deaminase was also reflected in a considerably increased ratio of ara-C/uracil arabinoside in the urine.
[14C] - 四氢尿苷（THU）是胞苷（CR）脱氨酶的强效抑制剂，静脉注射后，它能迅速且定量地从血液中清除，血浆半衰期约为1小时。排泄的主要途径是通过肾脏：50mg/kg剂量的大部分在12小时内排出，48小时内排泄基本完成。口服相同剂量时，胃肠道吸收约10%。在给予0.003mg/kg剂量的[3H] - 阿糖胞苷（ara - C）前15分钟，分别给予10mg/kg、25mg/kg和50mg/kg的THU，在5分钟至4小时的所有测量时间点，ara - C的血药浓度均升高约两倍，而ara - C的半衰期仅略有增加。仅在注射3H - ara - C后15分钟至1小时内，THU对ara - C脱氨的剂量相关效应明显。THU对CR脱氨酶的抑制作用还体现在尿中ara - C/阿糖尿苷的比例显著增加。
