Age-related differences in ophthalmic drug disposition I. Effect of size on the intraocular tissue distribution of pilocarpine in albino rabbits

Abstract

It has previously been documented that substantially different aqueous humour drug levels are observed in rabbits of different ages when the same dose of pilocarpine is instilled into the eye. Also, it has been shown that the aqueous humour volume ratio for rabbits of different ages can be used to predict aqueous humour levels of pilocarpine attained after topical dosing. In the present study, concentrations of pilocarpine in the cornea, aqueous humour, iris-ciliary body, lens, and vitreous humour were determined in both 20-day old and 60-day old rabbits following the topical administration of identical doses of drug. For tissues other than the aqueous humour and iris-ciliary body, consideration of only tissue size differences between rabbits of different ages will not suffice to explain the observed differences in pilocarpine concentration. Any attempt to develop rational age-related dosage modifications for ophthalmic drugs must include a consideration of functional and developmental differences as well as size effects.