Ocular disposition of topically applied histamine, cimetidine, and pyrilamine in the albino rabbit

Aqueous solutions of pyrilamine, cimetidine, and histamine were instilled into the eyes of albino rabbits and drug levels determined as a function of time in the cornea, conjunctiva, aqueous humor, and iris-ciliary body. For all three drugs, less than 1% of the applied dose penetrates to the aqueous humor. Moreover, cimetidine and histamine are significantly less bioavailable than pyrilamine. Both cimetidine and histamine appear to bind to precorneal mucin and thus exhibit binding to conjunctival tissue with subsequent low penetration into the cornea and prolonged peak times in the aqueous humor. In addition, both drugs show binding to the iris-ciliary body as well. The influence of solution pH on the penetration of these compounds was also investigated, and a factor of two increase in aqueous levels was noted for the pH range 5-8, which encompasses the pKa's for these compounds.