The ocular pharmacokinetics of ketanserin and its metabolite, ketanserinol, in albino rabbits

Ketanserin, a hypotensive drug with 5-HT2 receptor antagonism, when adminis tered by topical infusion of a 0.25% w/v solution by corneal and scleral ap plications, was found to lower intraocular pressure with four times more ac tivity than its metabolite, ketanserinol. Drug and metabolite were measured periodically in the corneal epithelium, corneal stroma/endothelium, aqueou s humor, iris/ciliary body, conjunctiva, sclera and lens during the infusio n period (0-120 min) and the postinfusion period (120-240 min) using a fluo rometric reversed-phase HPLC assay developed and verified for the research. The infusion results showed that drug entered the eye by both the corneal and scleral routes. Lateral diffusion occurred between the conjunctiva and corneal epithelium. Drug and metabolite were also detected in the untreated fellow eyes, suggesting contralateral systemic redistribution. In vitro me tabolism was studied and found to occur in the corneal epithelium, iris/cil iary body and bulbar and palpebral conjunctiva but not in the corneal strom a/endothelium, aqueous humor and sclera. From noncompartmental analysis, zero-order infusion rate constants, first-o rder absorption constants, mean residence time, volumes of distribution at steady state (Vss) and clearance (Cle) were obtained using equations specif ic to the topical infusion method. Vss and Cle of aqueous humor (0.972 mi a nd 13.55 mul/min) were greater than aqueous humor volume (0.311 mi) and tur nover rate (4.7 mul/min).