Penetration of mitomycin C in human bladder.
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)
Wientjes
M G
MG
Division of Urology, Ohio State University, Columbus 43210-1228.
Badalament
R A
RA
Wang
R C
RC
Hassan
F
F
Au
J L
JL
D000283:Administration, Intravesical; D000368:Aged; D000818:Animals; D003131:Combined Modality Therapy; D015925:Cryopreservation; D015653:Cystectomy; D004285:Dogs; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D013997:Time Factors; D014021:Tissue Preservation; D001743:Urinary Bladder / Q000378:metabolism* / Q000601:surgery; D001749:Urinary Bladder Neoplasms / Q000628:therapy
D016685:Mitomycin