DISTRIBUTION OF SALICYLATE IN PIGMENTED RABBIT OCULAR-TISSUES AFTER APPLICATION OF A PRODRUG, SODIUM MONOMETHYL TRISILANOL ORTHOHYDROXYBENZOATE - IN-VIVO AND EX-VIVO STUDIES

SMB (sodium monomethyl trisilanol orthohydroxybenzoate) is an organic complex of silicium and salicylate and the main component of a collyri um used in lens transparency abnormalities. Biotransformation and pene tration of salicylate in the whole eyeball have been investigated iii vivo after repeated instillations of those C-14-radiolabeled eyedrops. We also studied more accurately the salicylate diffusion within the l ens under ex vivo conditions. In vivo experiments demonstrated that 8 to 48 hours after the last instillation, radioactivity was detectable in most tissues and remained stable except in the chorioretina. The fo llowing gradient of distribution was observed: conjunctiva > cornea > iris-ciliary body > chorioretina > lens > vitreous body > aqueous humo r >> plasma and blood. The diffusion of the radiolabeled compound in l ens fibres was low, but a more important retention was observed in len s capsule. Though salicylate-metabolizing activities have been demonst rated in ocular tissues, no biotransformation could be detected under our experimental conditions. The lens SA-biotransformation activity wa s reported to be low and we can most probably consider that, in our ex vivo pharmacokinetic study, the lens metabolite amounts were negligib le compared with the salicylate levels. Under such conditions, results showed that the salicylate reached a steady-state between 6 and 12 ho urs of incubation, characteristic of a passive diffusion mechanism. Qu antitative image analysis of lens section autoradiograms revealed a mo re intense labeling of the anterior part of the lens and suggests that the lens epithelium may facilitate the salicylate diffusion. Furtherm ore, renal excretion is important since 40 % of the administered eyedr ops were eliminated during the study period.