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 collyrium used in lens transparency abnormalities. Biotransformation and penetration of salicylate in the whole eyeball have been investigated in vivo after repeated instillations of those 14C-radiolabeled eyedrops. We also studied more accurately the salicylate diffusion within the lens 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 following gradient of distribution was observed: conjunctiva > cornea > iris-ciliary body > chorioretina > lens > vitreous body > aqueous humor >> plasma and blood. The diffusion of the radiolabeled compound in lens fibres was low, but a more important retention was observed in lens capsule. Though salicylate-metabolizing activities have been demonstrated in ocular tissues, no biotransformation could be detected under our experimental conditions. The lens SA-biotransformation activity was reported to be low and we can most probably consider that, in our ex vivo pharmacokinetic study, the lens metabolite amounts were negligible compared with the salicylate levels. Under such conditions, results showed that the salicylate reached a steady-state between 6 and 12 hours of incubation, characteristic of a passive diffusion mechanism. Quantitative image analysis of lens section autoradiograms revealed a more intense labeling of the anterior part of the lens and suggests that the lens epithelium may facilitate the salicylate diffusion. Furthermore, renal excretion is important since 40% of the administered eyedrops were eliminated during the study period.
Laboratoire de Pharmacologie, Faculté de Médecine, Nice, France.
L
L
Chanalet
M
M
Ettaiche
C
C
Baudouin
P
P
Lapalus
D000818:Animals; D001345:Autoradiography; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D005123:Eye / Q000378:metabolism*; D007908:Lens, Crystalline / Q000378:metabolism*; D008297:Male; D009883:Ophthalmic Solutions; D009924:Organ Culture Techniques; D017646:Organosilicon Compounds / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000493:pharmacokinetics*; D011817:Rabbits; D012459:Salicylates / Q000493:pharmacokinetics*; D020156:Salicylic Acid; D012588:Scintillation Counting; D014018:Tissue Distribution
D003470:Culture Media; D009883:Ophthalmic Solutions; D017646:Organosilicon Compounds; D011355:Prodrugs; D012459:Salicylates; C092713:monomethyl trisilanol sodium orthohydroxybenzoate; D020156:Salicylic Acid