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Abstract #15748 Published in IGR 2-3
The ocular pharmacokinetics of ketanserin and its metabolite, ketanserinol, in albino rabbits
Schoenwald RD; Zhu JJournal of Ocular Pharmacology and Therapeutics 2000; 16: 481-495
Ketanserin, a hypotensive drug with 5-HT2 receptor antagonism, when administered by topical infusion of a 0.25% w/v solution by corneal and scleral applications, was found to lower intraocular pressure with four times more activity than its metabolite, ketanserinol. Drug and metabolite were measured periodically in the corneal epithelium, corneal stroma/endothelium, aqueous humor, iris/ciliary body, conjunctiva, sclera and lens during the infusion period (0-120 minutes) and the postinfusion period (120-240 minutes) using a fluorometric 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 metabolism was studied and found to occur in the corneal epithelium, iris/ciliary body and bulbar and palpebral conjunctiva but not in the corneal stroma/endothelium, aqueous humor and sclera. From noncompartmental analysis, zero-order infusion rate constants, first-order absorption constants, mean residence time, volumes of distribution at steady state (Vss) and clearance (Cle) were obtained using equations specific to the topical infusion method. Vss and Cle of aqueous humor (0.972 ml and 13.55 μl/min) were greater than aqueous humor volume (0.311 ml) and turnover rate (4.7 μl/min).
Dr. R.D. Schoenwald, Division of Pharmaceutics, College of Pharmacy, The University of Iowa, Iowa City 52242-1112, Iowa, USA. rschoenw@blue.weeg.uiowa.edu
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
