Dept. of Urology,

Jahn Ferenc South-Pest Teaching Hospital,

Budapest, Hungary

Sandor Lovasz MD. PhD.

High pressure intravesical drug deliveryHigh pressure intravesical drug delivery

Local, intravesical treatment - the most effective form of medical therapy in IC/PBSReduced side effect-profileHigher concentration of the agent at bladder surface

Intravesical drug is transferred by passive diffusion.

Influencing factors

Concentration gradient Pressure difference Time of impact Surface

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 deliveryHigh 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 deliveryHigh pressure intravesical drug delivery

High pressure intravesical drug deliveryHigh pressure intravesical drug delivery

• 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

This seems to be ideal!COSTS !!!COSTS !!!

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 deliveryHigh pressure intravesical drug delivery

High pressure intravesical drug deliveryHigh pressure intravesical drug delivery

Balloon’scharacristics

High pressure intravesical drug deliveryHigh pressure intravesical drug delivery

Kept continuously at max. 70cmH2Ofor 5-15minutes

Cystometry in a wide pressure-range:

Cysto-elastometry

High pressure intravesical drug deliveryHigh 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 deliveryHigh pressure intravesical drug delivery

High pressure intravesical drug delivery

Conclusions II

The method optimizes all parameters of passive drug diffusion

High pressure intravesical drug deliveryHigh pressure intravesical drug delivery

concentration gradient

pressure difference

time of impact

size of surface

thickness of barrierenhances efficacy of any intravesically used drugs

Conclusions III

All optimized parameters are standardized

at the same time.

High pressure intravesical drug deliveryHigh pressure intravesical drug delivery

Undisputed advantages

for basic research in the field of

topical treatment of IC/PBS.

Conclusions IV

Computerized analysis of pressure-volume relation of the bladder let us measure

novel physical characteristics of the bladder wall

High pressure intravesical drug deliveryHigh pressure intravesical drug delivery

Basic volume – independent of

patient’s sensitivity

Distensibility – quantitative meaure of

elastic propertiesSoftware freely available to anybody !Software freely available to anybody !

Conclusions V

High pressure intravesical drug deliveryHigh pressure intravesical drug delivery

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.

Dept. of Urology,

Jahn Ferenc South-Pest Teaching Hospital,

Budapest, Hungary

Sandor Lovasz MD. PhD.