The corneal penetration of trifluorothymidine, adenine arabinoside, and idoxuridine: a comparative study

Trifluorothymidine (F3TdR) and idoxuridine (IDU) were observed to penetrate through the cornea from the epithelial side at a greater rate than adenine arabinoside (ARA-A) during in vitro corneal perfusions. Removal of the epithelium increased the rate of penetration of F3TdR and IDU by about twofold and the rate of ARA-A penetration by fivefold. The kinetics of antiviral penetration did not display saturation points at high antiviral concentrations, thus indicating that these three antiviral drugs penetrate the cornea by nonfacilitated diffusion. The sole breakdown product detected following F3TdR penetration in vitro, in situ, and in controls was 5 carboxy-2'-deoxyuridine (5-COOH-2'-dUd). The sole breakdown product isolated during ARA-A penetration experiments was hypoxanthine arabinoside (ARA-HX), and control experiments indicated that ARA-A was stable at pH 7.6. IDU was degraded to 2'-deoxyuridine (dUd) in control experiments, but during corneal penetration experiments IDU was degraded to a mixture of dUd and iodouracil (IU).