PHARMACOKINETIC STUDY OF RECOMBINANT HUMAN EPIDERMAL GROWTH-FACTOR IN THE ANTERIOR EYE

This study investigated the pharmacokinetics of recombinant human epidermal growth factor (EGF) in the eyes of live rabbits and enucleated human eyes. After intracameral injection of 1.2-mu-Ci (1.1-mu-g) of I-125-EGF into rabbit eyes, tissues in the anterior segment were analyzed for uptake of I-125-EGF after 1, 2, 4, and 24 hr. The half-life of EGF during the initial 4 hr was 1.3 +/- 0.6 hr (+/- the confidence limit at P = 0.05) in the cornea, 0.7 +/- 0.4 hr in the iris, 1.9 +/- 0.9 hr in the lens, and 0.6 +/- 0.5 hr in the aqueous humor (n = 18 for each tissue). Between 4-24 hr, the percent retention of EGF in the tissues (relative to the initial amount in respective tissue) is in the order of lens > cornea > iris > aqueous humor. The kinetics of EGF uptake by excised human corneas was determined by incubating the endothelial surface with 1.2-mu-Ci/ml (100 ng/ml) of I-125-EGF for 4 hr at 37-degrees-C or 4-degrees-C. After 4 hr, the total amount of EGF accumulated in the corneas was 2.3 +/- 0.2 ng (+/- standard deviation; n = 6) at 37-degrees-C, and 1.4 +/- 0.1 ng at 4-degrees-C. In contrast, when the same concentration of I-125-EGF was exposed to the epithelial surface of human whole globe for 4 hr at 37-degrees-C, 0.49 +/- 0.24 ng (+/- SD; n = 4) was taken up by the cornea with Dexsol medium (Chiron, Irvine, CA) as the vehicle (0.13 +/- 0.03 ng with Duratears ointment [Alcon, Fort Worth, TX] as the vehicle). The EGF also penetrated the cornea into the anterior chamber, accumulating 4.3 +/- 2.1 ng/ml in the aqueous humor after 4 hr in the Dexsol vehicle and 0.43 +/- 0.06 ng/ml with the Duratears vehicle. These results suggest that predetermined doses of EGF could be delivered by topical application or intracameral infusion for therapeutic purposes to the corneal endothelium. However, it is critical to evaluate further whether such intraocular EGF exposure may be beneficial or detrimental to the lens and iris, which retain significant amounts of the administered EGF.