Pharmacokinetic of topical cyclosporin A in the rabbit eye.
3H labelled cyclosporin A (CS-A) eye drops (2% in castor oil) were applied in rabbits. When a single drop of 10 microliters was given CS-A reached a maximal concentration of 900-1400 ng/ml in the cornea 6 hr after application and then slowly decreased. A substantial level of 600-900 ng/ml was still present after 48 hr. When corneas were analysed for their cellular compartments, 67% of CS-A was found in the epithelium, 25% in the stroma (probably in keratocytes), and 8% in the endothelium. In corneas denervated by circular keratotomy, slightly reduced concentrations were found after surgery, the reduction was not therapeutically significant. Using the HPLC method a significant corneal metabolism of CS-A could be excluded. Scleral concentrations of CS-A as high as 180 ng/ml were found. Concentrations of CS-A in aqueous humor, lens, vitreous body and uvea/retina were below the therapeutic range.
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D003524:Cyclosporins / Q000032:analysis / Q000378:metabolism*; D005123:Eye / Q000032:analysis / Q000378:metabolism*; D007700:Kinetics; D007908:Lens, Crystalline / Q000378:metabolism; D008297:Male; D009883:Ophthalmic Solutions; D011817:Rabbits; D012160:Retina / Q000378:metabolism; D012590:Sclera / Q000378:metabolism; D014602:Uvea / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism
D003524:Cyclosporins; D009883:Ophthalmic Solutions