Adolphe A B, Glasofer E D, Troetel W M, Ziegenfuss J, Stambaugh J E, Weiss A J, Manthei R W
Cancer Chemother Rep. 1975 May-Jun;59(3):547-56.
We have investigated the distribution, biotranformation, and excretion of streptozotocin and its 14C- and 3H-labeled metabolities in 15 patients with advanced cancer. Streptozotocin was detected in the plasma during the first 3 hours after administration while radioactive products were present for longer than 24 hours. No unchanged streptozotocin was detected in the cerebrospinal fluid (CSF); however, 14C-labeled metabolites were detected in the 2-hour CSF sample in a concentration equivalent to the 2-hour plasma level. H activity is the CSF was not detected at this time period. Radioactivity measured in biopsied tissues indicated that streptozotocin labeled with 14C and 3H or its metabolites penetrated tumor tissue. 14C tissue levels were found to approximate plasma levels; however, 3H levels were found to be greater than the corresponding plasma levels. Fifteen percent of the total dose of streptozotocin administered was recovered in the urine. 3H-labeled metabolites were recovered in excess of 60% in the urine, and approximately 30% of the 14C-labeled metabolites were recovered in the urine during a similar interval. Less than 1% of the administered 14C and 3H was recovered in the feces. 14C-labeled CO2 was also recovered, although quantitative recovery was not attained. At least three major metabolites of streptozotocin were detected in the urine by radiochromatography. Two metabolites contained only 3H and one metabolite contained both 14C and 3H in the same ratio as administered.
我们研究了链脲佐菌素及其14C和3H标记代谢物在15例晚期癌症患者体内的分布、生物转化和排泄情况。给药后最初3小时内在血浆中检测到链脲佐菌素，而放射性产物存在超过24小时。在脑脊液（CSF）中未检测到未变化的链脲佐菌素；然而，在2小时的脑脊液样本中检测到14C标记的代谢物，其浓度与2小时血浆水平相当。在此时间段内未在脑脊液中检测到H活性。活检组织中的放射性测量表明，用14C和3H标记的链脲佐菌素或其代谢物穿透了肿瘤组织。发现14C组织水平接近血浆水平；然而，发现3H水平高于相应的血浆水平。给药的链脲佐菌素总剂量的15%在尿液中回收。3H标记的代谢物在尿液中的回收率超过60%，在类似时间段内，约30%的14C标记代谢物在尿液中回收。粪便中回收的给药14C和3H不到1%。还回收了14C标记的二氧化碳，尽管未实现定量回收。通过放射色谱法在尿液中检测到至少三种链脲佐菌素的主要代谢物。两种代谢物仅含3H，一种代谢物同时含有14C和3H，其比例与给药时相同。
