Method of high pressure intravesical drug delivery Sandor Lovasz MD. PhD. Dept. of Urology, Jahn Ferenc South-Pest Teaching Hospital, Budapest, Hungary

High pressure intravesical drug delivery Local, intravesical treatment - the most effective form of medical therapy in IC/PBS Reduced side effect-profile Higher concentration of the agent at bladder surface Intravesical drug is transferred by passive diffusion. Influencing factors Concentration gradient Pressure difference Time of impact Surface

High pressure intravesical drug delivery Diuresis acts confusing in intravesical therapy. Concentration reduction (dilution) Reduction of time of exposure (urination) Both parameters are adversely influenced + diuresis is highly variable and unpredictable Efforts are made to reduce influence of diures.

High pressure intravesical drug delivery Using - higher concentration - minimized diuresis - alkalized urine Mitomycin C proved to be significantly more effective in a Phase III multicenter clinical trial. Au, Badalament, Wientjes et al.: Methods to Improve Efficacy of Intravesical Mitomycin C: Results of a Randomized Phase III Trial Journal of the National Cancer Institute 2001

High pressure intravesical drug delivery This seems to be ideal! COSTS !!! 20-40ml filling volume of intravesical drug low intravesical pressure small bladder surface thick bladder mucosa dilution by diuresis 400-500ml filling volume of intravesical drug high intravesical pressure (50-70cmH2O) great bladder surface thin bladder mucosa no dilution by diuresis due to high pressure

High pressure intravesical drug delivery 1. Fill medication into empty bladder 2. Place special dilator balloon catheter 3. Blow up the balloon under continuous pressure control - measured inside the balloon 3. Drug is being pressed into the mucosa of the bladder

High pressure intravesical drug delivery Balloon’s characristics

High pressure intravesical drug delivery Kept continuously at max. 70cmH2O for 5-15minutes Cystometry in a wide pressure-range: Cysto-elastometry

High pressure intravesical drug delivery

High pressure intravesical drug delivery Conclusions I Intravesical drug administration combined with Simultaneous balloon dilation of the bladder provides the basically new method of High pressure intravesical drug delivery

High pressure intravesical drug delivery Conclusions II The method optimizes all parameters of passive drug diffusion concentration gradient pressure difference time of impact size of surface thickness of barrier enhances efficacy of any intravesically used drugs

High pressure intravesical drug delivery Conclusions III All optimized parameters are standardized at the same time. Undisputed advantages for basic research in the field of topical treatment of IC/PBS.

High pressure intravesical drug delivery Conclusions IV Computerized analysis of pressure-volume relation of the bladder let us measure novel physical characteristics of the bladder wall Basic volume – independent of patient’s sensitivity Distensibility – quantitative meaure of elastic properties Software freely available to anybody !

High pressure intravesical drug delivery Conclusions V Our basic goal was to establish an „open source project” for research of efficacy enhencement of topical, intravesical medical treatment (not just) for IC/PBS.

Thank you for your attention Jahn Ferenc South-Pest Teaching Hospital,    Sandor Lovasz MD. PhD. Dept. of Urology, Jahn Ferenc South-Pest Teaching Hospital, Budapest, Hungary