The bladder urothelium: passive permeability and intravesical drug passive diffusion.

The urothelium allows the urinary bladder to minimize alterations in the composition of the urine during storage. Modifications of either cellular or tight junctions permeability alter the efficacy of the barrier properties of urothelium. Changes within the physiological range for urine pH, calcium or urea concentrations do not alter the barrier function of the urothelium, as determined from measurements of the transepithelial resistance. The barrier function may be destroyed by bacterial infection, toxic chemicals, or mechanical damage, but also by non-bacterial, non-chemical inflammatory response. Direct administration of drug solutions into the bladder through a urethral catheter overcomes systemic adverse events of drugs used for bladder disease. Indeed, this treatment modality represents a complex and not completely understood process. Several factors influence the drug transport across the urothelium: the barrier properties of the urothelium itself, pressure gradients, times of exposure, molecular weight and configuration and degree of ionization of the drugs. Further experimental studies and laboratory experiences are needed to transform an empirical methodology, that is intravesical drug passive diffusion, in a really scientific treatment modality.