Therapeutic index of epinephrine and dipivefrin with nasolacrimal occlusion

We assessed the effect of nasolacrimal occlusion on the therapeutic index of the adrenoreceptor agonists in healthy volunteers and patients with glaucoma. Nasolacrimal occlusion did not significantly alter the response to 2% epinephrine or to 0.1% dipivefrin in healthy subjects, suggesting that both 2% epinephrine and 0.1% dipivefrin are at the top of the dose-response curve. When 0.5% epinephrine with nasolacrimal occlusion was tested in patients with glaucoma, effects were noticeable at four and eight hours (P less than .05), but not at 12 hours. For 2% epinephrine, there was no significant difference at any measurement time. Epinephrine (1%) with and without nasolacrimal occlusion gave results similar to those of 2% epinephrine, suggesting that 1% epinephrine is also at the top of the dose-response curve. Nasolacrimal occlusion did not increase the ocular hypotensive effect of either of these concentrations. Because dipivefrin, the most widely used formulation in this class, is a prodrug of epinephrine that has a corneal penetration approximately 17 times that of epinephrine, 0.05% dipivefrin, every 12 hours, might be an adequate dosage for maximal effect. Although nasolacrimal occlusion did not alter the drug effect of 0.1% dipivefrin, preventing as much drug as possible from reaching the systemic circulation is desirable.