Drug-Absorption Analysis from Pharmacological Data II: Transcorneal Biophasic Availability of Tropicamide

Following an ophthalmic dose, the mydriatic drug, tropicamide, may traverse the cornea to reach its vicinal sites of action (biophase) directly or indirectly gain access subsequent to its systemic absorption. The latter route of entry into the biophase may be attributed to fluid volume loss and scleral absorption. A means by which the relative quantities of the drug absorbed transcorneally directly into the biophase and indirectly following systemic absorption at any time can be discerned from concomitant measurements of pupillary diameters in drug-treated and untreated eyes is described. However, except at very high dosage, the observed magnitude of effects in the control eye were insufficient for this method to be practical for tropicamide. The determination of the total relative quantities of drug ultimately dissipated from the absorption site by routes other than transcorneal absorption into the biophase was, however, approximated from measurements performed on the treated eye alone. Semilogarithmic plots of the time course of transcorneal drug passage were linear, indicating the biophasic availability of tropicamide to occur through the operation of apparent first-order processes. A comparison of pharmacological and biokinetic parameters characterizing the mydriatic behavior of tropicamide administered in vehicles having a pH of 5.0 and 7.4 is presented.