Hexaminolevulinate

After intravesical instillation of hexaminolevulinate, porphyrins will accumulate intracellularly in bladder wall lesions. The intracellular porphyrins (including PpIX) are photoactive, fluorescing compounds which emit red light upon blue light excitation. As a result, premalignant and malignant lesions will glow red on a blue background. False fluorescence may be seen as a result of inflammation.

In vitro studies have shown a considerable build-up of porphyrin fluorescence in malignant urothelium after exposure to hexaminolevulinate.

In humans, a higher degree of accumulation of porphyrins in lesions compared to normal bladder urothelium has been demonstrated with hexaminolevulinate. After instillation of the reconstituted solution for 1 hour and subsequent illumination with blue light, tumours can be readily visualized by fluorescence.

In vivo autoradiography studies in rats after intravesical administration have shown high concentrations of hexaminolevulinate in the bladder wall.

After intravesical instillation of radiolabelled hexaminolevulinate in healthy volunteers, the systemic bioavailability of total radioactivity was approximately 5-10%.

Studies in rats and dogs have not indicated any risks for systemic toxicity.

Seven-day intravesical tolerance studies, without light exposure, were performed in rats and dogs. The study in rats showed cases of leukocytosis, suggesting a proinflammatory activity of hexaminolevulinate. Cases of azotemia, red coloured urine and weight loss were also seen. In dogs treated with hexaminolevulinate there was a marginally increased incidence and severity of transition cell hyperplasia and basophilia in the urinary epithelium.

A local lymph node assay in mice has demonstrated that hexaminolevulinate has a potential to cause skin sensitisation.

Potential genotoxicity has been investigated in vitro in procaryotic and eucaryotic cells in the presence and absence of photoactivating illumination and in vivo. All the studies of genotoxic potential were negative (Ames test, TK assay, in vivo micronucleus cell model, chromosome aberrations in CHO cells, and Comet assay on vesical samples from a dog local tolerance study with blue light activation).

Reproductive toxicity has been investigated in rats and rabbits. The incidences of embryo-fetal mortality, fetal weights, and the fetal abnormalities and variants, including skeletal ossification parameters did not indicate any obvious effect of treatment. There were no effects on female fertility and on early embryonic development when investigated in rats.

Carcinogenicity studies have not been performed with hexaminolevulinate.