Concentration-depth profiles of mitomycin-C in the human bladder wall after passive diffusion, thermochemotherapy, and electromotive drug administration.

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4568 Background: Device-assisted intravesical mitomycin-C (MMC), including electromotive administration (EMDA) and thermochemotherapy (TC), shows promise and offers the prospect of greater efficacy than passive diffusion (PD). Integration of drug delivery with tissue pharmacodynamic data provides a means to rational design of intravesical treatments. We compared concentration-depth profiles of MMC in the bladder wall after PD, TC and EMDA. Methods: During each experiment, 3 full thickness sections of viable human bladder wall were placed between the two chambers of individual diffusion cells, with urothelium exposed to donor compartments containing 40 mg of MMC in 100 ml water and with serosa-facing receptor compartments containing 100 ml of 0.9% NaCl solutions. Fifteen paired experiments were conducted over a 30-min period. In TC experiments, the two chamber cells were placed in a 37°C incubator with the donor compartments filled with heated MMC solutions at 44°C. In EMDA experiments an anode was placed in the donor compartment and a cathode in the receptor compartment. The electrodes were connected to the current generator and experiments were performed with pulsed direct current of 23 mA. No electric current or TC were applied in PD control experiments. Bladder wall sections were cut serially into 40-mm slices parallel to the urothelium, the tissues were homogenized and analyzed by high-performance liquid chromatography for MMC concentration. Results: Concentration-depth profiles of MMC in bladder wall tissues following PD, TC or EMDA are reported below (Table). Data are expressed as μ g of MMC/mg of wet tissue, the means ± standard error of the mean (SEM) of 15 replicates per experimental group. Conclusions: EMDA significantly enhances MMC transport into all of the layers of the bladder wall, compared to both PD and TC. The latter had no effect whatsoever on MMC transport into bladder wall tissues compared to PD. PD TC EMDA p value Urothelium (80-200 μ m) 53.057 ± 8.240 58.270 ± 8.820 207.991 ± 23.440 <0.001 Lamina propria(200-1,200 μ m) 18.095 ± 2.139 20.935 ± 3.205 85.339 ± 5.882 <0.001 Muscle layer(1,200-4,000 μ m) 2.120 ± 0.326 2.424 ± 0.297 24.888 ± 3.645 <0.001 No significant financial relationships to disclose.