Corneal metabolism of pilocarpine in pigmented rabbits.

Cornea, aqueous humor, and iris-ciliary body levels of pilocarpine and its metabolite pilocarpic acid were determined in mixed-breed rabbits following topical dosing with 25 microliters of 1 X 10(-2) M pilocarpine. From the time-drug concentration profile it is clear that extensive metabolism of pilocarpine occurs in the cornea of pigmented rabbits. This finding contrasts sharply with similar studies in albino rabbits where relatively low levels of pilocarpine acid were observed. It is estimated that the first-order metabolism rate constant in albino rabbits is approximately two orders of magnitude smaller than in pigmented animals. A significant observation from this finding is the possibility that the reported greater dose requirement for heavily pigmented individuals may not be due to drug-pigment binding alone but also to extensive corneal drug metabolism.