Tsushima T
Hinyokika Kiyo. 1985 Nov;31(11):1945-56.
4'-Epi-adriamycin (EPI) is a new derivative of adriamycin (ADM). The cytotoxic effect of EPI on the T24 cell line, an established cell line from human urinary bladder carcinoma, the distribution of the drug in blood, urine and tissues of various organs and histopathological change in the bladder mucosa in dogs following intravesical instillation of the drug, were studied. The cytotoxicity of EPI on the cultured T24 cells was examined by a colony formation method. After 2 hours exposure, EPI was slightly less cytotoxic than ADM, but showed higher cytotoxicity than mitomycin C or aclacinomycin A. The drug levels in blood, urine and tissues were measured by HPLC following bladder instillation in Beagle dogs with bilateral cutaneous ureterostomy. They were elevated in proportion to the drug concentration instilled intravesically. After 50 mg of EPI dissolved in 10 ml of physiological saline was instilled intravesically, the blood levels of EPI were not elevated significantly and reached the maximum levels of only 0.222 microgram/ml. The total amount of EPI excreted into the urine during the 10 hours after instillation was 389 micrograms which was equivalent to 0.78% of instilled EPI. The tissue levels of 50 mg of EPI after 6 hours retention were 1216 +/- 1094 micrograms/g in the bladder mucosa, 259 +/- 250 micrograms/g in the bladder muscular layer, 7.65 +/- 1.19 micrograms/g in the iliac node, 22.1 +/- 4.8 micrograms/g in the cortex of kidney, 15.1 +/- 3.8 micrograms/g in the medulla of kidney, 11.3 +/- 1.0 micrograms/g in liver and 5.80 +/- 1.20 micrograms/g in the heart. To examine the effect of the drug on the bladder mucosa, 50 mg of EPI was instilled intravesically. After 6 hours retention, bladder mucosa was observed through a microscope and a scanning electron microscope. Only exfoliation in the mucosa was observed sporadically and no histological change was observed in the submucosal layer. The above results suggest that EPI is a suitable drug for intravesical chemotherapy to bladder cancers.
4'-表阿霉素（EPI）是阿霉素（ADM）的一种新衍生物。研究了EPI对T24细胞系（一种源自人膀胱癌的成熟细胞系）的细胞毒性作用、药物在血液、尿液及各器官组织中的分布以及犬膀胱内灌注该药物后膀胱黏膜的组织病理学变化。采用集落形成法检测EPI对培养的T24细胞的细胞毒性。暴露2小时后，EPI的细胞毒性略低于ADM，但高于丝裂霉素C或阿克拉霉素A。在双侧皮肤输尿管造口的比格犬膀胱内灌注后，通过高效液相色谱法测定血液、尿液和组织中的药物水平。它们与膀胱内灌注的药物浓度成比例升高。将50mg EPI溶解于10ml生理盐水中膀胱内灌注后，EPI的血液水平未显著升高，最高仅达到0.222μg/ml。灌注后10小时内排泄到尿液中的EPI总量为389μg，相当于灌注EPI的0.78%。保留6小时后，50mg EPI在膀胱黏膜中的组织水平为1216±1094μg/g，在膀胱肌层中为259±250μg/g，在髂淋巴结中为7.65±1.19μg/g，在肾皮质中为22.1±4.8μg/g，在肾髓质中为15.1±3.8μg/g，在肝脏中为11.3±1.0μg/g，在心脏中为5.80±1.20μg/g。为检测该药物对膀胱黏膜的影响，膀胱内灌注50mg EPI。保留6小时后，通过显微镜和扫描电子显微镜观察膀胱黏膜。仅偶尔观察到黏膜剥脱，黏膜下层未观察到组织学变化。上述结果表明，EPI是一种适用于膀胱癌膀胱内化疗的药物。
