Yamauchi H, Sasano M & Iso T
pH dependency of effect of topically applied dipivefrine hydrochloride on intraocular pressure and pupil size in rabbits: comparative studies with epinephrine.

Jpn J Ophthalmol, 32(2): 187-195, 1988
ISSN: 0021-5155 Japanese Journal of Ophthalmology (PubMed)

Abstract
The pH and dose dependencies of topically applied dipivefrine hydrochloride (DPE) on intraocular pressure (IOP) reduction and mydriasis were compared with those of epinephrine bitartrate (EPI) in normal rabbits. Statistically significantly greater IOP lowering and mydriatic effects of DPE solutions were achieved by increasing their pH from 3 to 6 or their concentrations from 0.02% to 0.1%. The ocular hypotensive and mydriatic effects of EPI also depended on their concentrations, but not on their pH. On the other hand, blink rates of rabbits following topical application of DPE tended to be reduced by the increase of pH, while they were not influenced by the concentrations. From these results, it was indicated that the pharmacological effects of DPE were augmented about 3 times by increasing the pH of its solutions from 3 to 5, which also was associated with reduction of ocular irritation, while the effects of EPI were not altered by the changes of pH. As the result of the increase of pH from 3 to 5, DPE became about 50 times more potent than EPI as a ocular hypotensive agent.