UPTAKE AND DISTRIBUTION OF INTRAVENOUSLY OR INTRAVESICALLY ADMINISTERED PHOTOSENSITIZERS IN THE RAT

Photodynamic therapy using i.v. injected porphyrin photosensitizers ha ve been used to treat selected cases of superficial bladder cancer. Si nce cutaneous photosensitivity, lasting 6-8 weeks, is a well known und esirable side effect of this therapy, we instilled the photosensitizer s intravesically in rats and compared the uptake of photosensitizers i n different tissues by this route of administration with the uptake af ter intravenous injection. The intravesical mode of delivery enhanced photosensitizer uptake in the bladder wall, while giving low concentra tions in extravesical organs. Intravesical instillation of the photose nsitizers may therefore increase their efficacy and reduce phototoxici ty as compared with intravenous injection. Comparing the results obtai ned by two assays, one based on porphyrin fluoroscence and the other b ased on the application of radioactively labelled photosensitizers, it was concluded that the i.v. administration route may result in tissue uptake of significant amounts of aggregated non-fluorescent, supposed ly inactive drug, while the intravesical administration led to less up take of aggregates relative to active drug monomers.