title: Therapeutic index of pilocarpine, carbachol, and timolol with nasolacrimal occlusion.
abstract: We assessed the effect of nasolacrimal occlusion on the therapeutic index of various antiglaucoma medications in healthy volunteers and patients with glaucoma. Nasolacrimal occlusion used with pilocarpine 2% every 12 hours gave the maximal ocular hypotensive response. Carbachol 1.5% every 12 hours with nasolacrimal occlusion gave the maximal response for this drug. For timolol, nasolacrimal occlusion collapsed the dose-response curve and extended the duration of action. A final trial of carbachol added to timolol with nasolacrimal occlusion showed that timolol 0.25% and carbachol 1.5% every 12 hours gave the maximal response for this combination. Our findings suggest that most of the commercially used ocular hypotensive agents can achieve the same maximal effect with lower concentrations and less frequent administration (never exceeding every 12 hours) than are currently recommended should nasolacrimal occlusion be performed. Furthermore, nasolacrimal occlusion should markedly decrease the systemic absorption of topical ocular drugs and lessen the chance of systemic side effects.
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; D002217:Carbachol / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002908:Chronic Disease; D003315:Cornea / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D007767:Lacrimal Duct Obstruction; D009301:Nasolacrimal Duct; D010862:Pilocarpine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010919:Placebos; D013999:Timolol / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D010919:Placebos; D010862:Pilocarpine; D013999:Timolol; D002217:Carbachol