Clinical pharmacokinetics of the eye. Proctor lecture.

Pharmacokinetics of instilled drugs in the human eye is reviewed. The behavior of drugs in the conjunctival cul-de-sac is discussed, and the loss rates with various vehicles are estimated. Kinetics of intraocular drug penetration follows the same pattern in human and rabbit eyes. From results of rabbit experiments, various pharmacokinetic coefficients are computed, including the permeability of the corneal epithelium. Also, with use of published data in human aqueous, the corneal permeability, apparent absorption, and elimination rate constants are calculated for some drugs in the human eye. From the anesthetic response of the cornea the apparent elimination rate constants of the surface anesthetics are obtained. The pupil response is converted to a response parameter proportional to the biophase drug concentration. The time course of its changes conforms with the kinetics of intraocular drug penetration, and the apparent absorption and elimination rate constants are computed for various drugs. The latter constant becomes smaller with increased ocular pigmentation. Use of the relative bioavailability concept permits comparison of drug absorption efficiency among various vehicles. Pharmacokinetic coefficients are also obtained for the cycloplegic responses. The intraocular pressure response is analyzed, and it is suggested that the reduction ratio in the outflow pressure, outflow resistance, and the aqueous formation rate be used for dose-response studies. The rate of effect disappearance is defined and is given for three beta-adrenergic blocking agents.