Hirst D G, Horsman M R, Brown J M, Hazlehurst J L
Int J Radiat Oncol Biol Phys. 1984 Sep;10(9):1641-5. doi: 10.1016/0360-3016(84)90519-4.
The nitroimidazole SR-2508 is currently being tested clinically as a radiosensitizer. Its relatively low toxicity allows it to be used at higher doses than misonidazole so that its potential as a chemosensitizer is also of considerable interest. Multiple injections of SR-2508 were given to SCC VII/St tumor-bearing mice to achieve a clinically realistic plasma concentration of approximately 300 micrograms/ml over 8 hrs. Single doses of melphalan (L-PAM) or cyclophosphamide (CY) were given at different times after the first SR 2508 injection. With L-PAM, a delay of at least 2 hr was necessary before enhancement of L-PAM cytotoxicity was observed. A similar result was obtained when a simulation was carried out with SCC VII/St tumor cells in vitro. Results with CY were less clear, although the most consistent enhancement was observed when a 4 to 8 hr interval elapsed between the beginning of SR 2508 exposure and the CY injection. In general, although precise timing was not essential for enhancement, an interval of at least 4 hr is recommended between the administration of SR 2508 and either alkylating agent. This is particularly important for L-PAM where no enhancement would be expected if the drugs were given simultaneously.
硝基咪唑SR - 2508目前正在作为一种放射增敏剂进行临床测试。其相对较低的毒性使其能够以比米索硝唑更高的剂量使用，因此其作为化学增敏剂的潜力也备受关注。对荷SCC VII/St肿瘤的小鼠多次注射SR - 2508，以在8小时内达到约300微克/毫升的临床实际血浆浓度。在首次注射SR - 2508后的不同时间给予单剂量的美法仑（L - PAM）或环磷酰胺（CY）。对于L - PAM，在观察到L - PAM细胞毒性增强之前，至少需要延迟2小时。在体外对SCC VII/St肿瘤细胞进行模拟时也得到了类似的结果。CY的结果不太明确，尽管在SR - 2508暴露开始与CY注射之间间隔4至8小时时观察到了最一致的增强效果。一般来说，虽然精确的时间安排对于增强效果并非必不可少，但建议在给予SR - 2508与任何一种烷基化剂之间间隔至少4小时。这对于L - PAM尤为重要，如果同时给予这两种药物，则不会预期有增强效果。
