Transcript High pressure intravesical drug delivery High pressure intravesical

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
• 20-40ml filling volume of intravesical drug
• low intravesical pressure
This seems to be ideal!
• small bladder surface
• thick bladder mucosa
• dilution by diuresis
COSTS !!!
• 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
enhances efficacy of any intravesically used drugs
thickness of barrier
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.
Sandor Lovasz MD. PhD.
Dept. of Urology,
Jahn Ferenc South-Pest Teaching Hospital,
Budapest, Hungary