Pharmacokinetics of topical ocular phenylephrine HCl.

The rates of corneal penetration and efflux of phenylephrine (PE) and its metabolites were found to be limited by the epithelium. The rate constant for corneal penetration as measured in a lucite block perfusion system was 1.06 X 10(-3) hr-1 when the epithelium was present and 1.25 X 10(-2) hr-1 when the epithelium was denuded. Epithelial removal reduced the half-time (t1/2) for corneal efflux of PE from 24 min to 6 min. Ocular absorption of topically applied 0.1% PE (three 30-microliters instillations at five-minute intervals) was increased when the corneal epithelium was removed prior to application. Corneal concentrations of PE increased threefold, aqueous humor concentrations increased ten to 13-fold and iris/ciliary body concentrations increased sixfold upon epithelial removal. HPLC analysis suggested that the corneal epithelium was responsible for the metabolic degradation of PE, which occurred following topical instillation of PE.