Enhanced ocular penetration of the methyl ester of (+/-) alpha-methyl-para-tyrosine after lontophoresis.

A comparative study of ocular penetration of the methyl ester of (+/-) alpha-methyl-para-tyrosine after the intraperitoneal route of administration versus that after the more localized subconjunctival and iontophoretic routes has been undertaken. Levels of alpha-methyl-para-tyrosine in the aqueous humor of rabbits were measured both 2 and 6 hr affter drug administration. Changes in norepinephrine levels in iris and ciliary processes at these time points were also determined. The results indicated that the highest concentrations of the drug in aqueous were reached 2 hr after iontophoresis (40 mg/ml, positive pole, 3 mamp for 5 min), at which time norepinephrine tissue levels were reduced by 20%. While norepinephrine levels 2 hr after the intraperitoneal route (100 mg/kg) remained unchanged, those after subconjunctival injection (5 mg in 0.3 ml saline) were slightly but significantly elevated. By 6 hr after alpha-methyl-para-tyrosine administration by each route, only small amounts of the drug were detected in aqueous humar. Norepinephrine levels in iris and ciliary processes after iontophoresis, however, were still depleted by 20%. Norepinephrine stores after the intraperitoneal route likewise were reduced by 20%, while those after subconjunctival injection did not differ from control. These results suggest that iontophoresis, in addition to confining the site of drug action, actually enhances ocular penetration.