A continuous sampling technique for quantitatively measuring transcorneal penetration in vivo.

This paper reports on a dynamic technique for measuring penetration of radiolabeled substances topically applied to the cornea! surface of anesthetized dogs. The agent was collected for analysis by perfusion of the aqueous chamber with isotonic saline as it traversed the corneal tissue. During collection of the perfusate over a period of 80 to 100 minutes, nearly physiologic conditions were maintained in that the blood-aqueous barrier remained intact and changes in intraocular pressure were slight and gradual. After collection, the perfusate was analyzed and steady-state rates of penetration were estimated by plotting cumulative amounts of agent collected as a function of time. In order to take into account loss of agent by absorption from the aqueous chamber during the collection of perfusate, a correction factor was applied. In these experiments, the average loss of agent under equilibrium conditions was 14 per cent. This absorptive loss was significantly less in the mydriatic than in the control or the miotic eye. Using the technique described, diethyl-o-cresyl phosphate (DECP), an organic lipophilic liquid with limited aqueous solubility, traversed the intact dog cornea at about 19 fig per square centimeter per minute under steady-state conditions. Removal of the epithelium did not alter this rate significantly.