title: Therapeutic index of epinephrine and dipivefrin with nasolacrimal occlusion.
abstract: 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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Louisville, School of Medicine, Kentucky 40292.
authors.forename: T J
authors.initials: TJ
authors.lastname: Zimmerman
authors.forename: M
authors.initials: M
authors.lastname: Sharir
authors.forename: G F
authors.initials: GF
authors.lastname: Nardin
authors.forename: M
authors.initials: M
authors.lastname: Fuqua
mesh_terms: D000042:Absorption; D003315:Cornea / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004837:Epinephrine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D007767:Lacrimal Duct Obstruction; D009301:Nasolacrimal Duct; D010919:Placebos
chemical_list: D010919:Placebos; C015173:dipivefrin; D004837:Epinephrine