Wientjes M G, Badalament R A, Wang R C, Hassan F, Au J L
Division of Urology, Ohio State University, Columbus 43210-1228.
Cancer Res. 1993 Jul 15;53(14):3314-20.
The penetration of mitomycin C (MMC) in bladder tissue was studied in patients who received intravesical chemotherapy at the time of radical cystectomy. An intravesical dose of MMC (20 mg/40 ml) was instilled and maintained in the bladder for 60 to 120 min at which time the solution was drained. Within 10 to 60 min after draining the drug solution, the bladder vasculature was ligated, and the bladder was removed. Tissues were sectioned serially in layers parallel to the urothelium and analyzed for MMC concentration. Of the 24 patients evaluated, 17 patients had a low final MMC concentration in urine (< 66 micrograms/ml) or had the MMC solution drained more than 30 min before ligation of the blood vessels. Among these 17 patients, the concentration in the urothelium was measurable in only 4 patients, while the concentrations in deeper tissues were not measurable. In the remaining 7 patients where the urine concentration was > 120 micrograms/ml and where the vasculature was ligated within 30 min after the MMC solution was drained, the bladder wall contained significant MMC concentrations. The drug penetration was studied in the latter 7 patients, using sections of bladder wall that were grossly normal and non-tumor bearing. Concentrations in the bladder wall declined semilogarithmically with tissue depth from the urothelium to the deep muscle and reached a plateau at about 2000 microns depth. The median MMC concentrations were 5.6 micrograms/g in the urothelium and lamina propria interface, 2.7 micrograms/g in the lamina propria, and 0.9 microgram/g in the muscularis. The distance over which the MMC concentration decreased by one-half was about 500 microns. The concentration ratio between the urine and urothelium/lamina propria interface was about 35-fold. The mean plasma concentrations were 0.003, 0.1, and 0.4% of the mean concentration in urine, urothelium, and the averaged bladder tissue concentrations, respectively. Paired superficial tumor and normal tissues were obtained from 5 bladders. In 4 of 5 cases, the concentration in tumors was higher than in normal tissues, while the reverse was seen in the remaining tumor. In one sessile bladder tumor a complete concentration-depth profile could be obtained. While the concentrations in the tumor tissue were 2-3-fold higher than that in the adjacent normal tissue, the rate of concentration declined with respect to tissue depth and hence the distance over which the MMC concentration decreased by one-half was similar in both tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
在接受根治性膀胱切除术时接受膀胱内化疗的患者中，研究了丝裂霉素C（MMC）在膀胱组织中的渗透情况。膀胱内注入MMC剂量（20mg/40ml），并在膀胱内保留60至120分钟，然后排出溶液。在排出药物溶液后10至60分钟内，结扎膀胱血管，然后切除膀胱。将组织切成平行于尿路上皮的连续层，并分析MMC浓度。在评估的24例患者中，17例患者尿液中最终MMC浓度较低（<66μg/ml），或在结扎血管前30多分钟排出了MMC溶液。在这17例患者中，仅4例患者的尿路上皮中可检测到MMC浓度，而更深层组织中的浓度无法检测到。在其余7例患者中，尿液浓度>120μg/ml，且在排出MMC溶液后30分钟内结扎了血管，膀胱壁中含有显著的MMC浓度。在这后7例患者中，使用大体正常且无肿瘤的膀胱壁切片研究了药物渗透情况。膀胱壁中的浓度从尿路上皮到深层肌肉随组织深度呈半对数下降，并在约2000微米深度处达到平台期。尿路上皮和固有层界面的MMC中位数浓度为5.6μg/g，固有层为2.7μg/g，肌层为0.9μg/g。MMC浓度降低一半的距离约为500微米。尿液与尿路上皮/固有层界面的浓度比约为35倍。平均血浆浓度分别为尿液、尿路上皮和平均膀胱组织浓度的0.003%、0.1%和0.4%。从5个膀胱中获取了配对的浅表肿瘤组织和正常组织。在5例中的4例中，肿瘤中的浓度高于正常组织，而在其余肿瘤中则相反。在一个无蒂膀胱肿瘤中，可以获得完整的浓度-深度分布图。虽然肿瘤组织中的浓度比相邻正常组织高2至3倍，但浓度随组织深度下降，因此MMC浓度降低一半的距离在两种肿瘤中相似。（摘要截取自400字）
