Pharmacokinetics and safety of transcorneal iontophoresis of tobramycin in the rabbit.

Abstract

Transcorneal iontophoresis of tobramycin in normal eyes of New Zealand white rabbits was compared to an eye cup control and application of fortified topical drops. Iontophoresis was performed with 25 mg/ml of tobramycin at 0.8 mAmps for 10 or 5 min. The eye cup with 25 mg/ml of tobramycin was placed on the eye for 10 min without current. Topical fortified drops (13.6 mg/ml) were applied every half hour for 4 hr. Epithelium, stroma, and aqueous humor were assayed separately at 1, 4, 8 and 16 hr after treatment. The eyes were examined using the slit-lamp biomicroscope before and immediately after the treatment, and prior to sacrifice. Two eyes were examined by light and scanning electron microscopy 5 and 10 min after iontophoresis. Iontophoresis yielded significantly higher tobramycin concentrations than the eye cup or fortified topical drops at 1 hr and 4 hr after treatment (P = 0.001). In all treated eyes, iontophoresis resulted in epithelial edema and mucous discharge, which resolved by 24 hr after the treatment. Histologically there was evidence of epithelial disruption in the superficial layer after 5 min of iontophoresis and in all layers of the epithelium after 10 min of iontophoresis. Iontophoresis is a relatively safe, effective method to deliver medications to ocular tissues and may be useful alone or as an adjunct to current modes of antimicrobial chemotherapy.