title: Systemic absorption of insulin delivered topically to the rat eye.
abstract: Insulin administration in eye drops containing 1% saponin caused a rapid and reproducible reduction in blood levels of D-glucose in anesthetized rats; insulin eye drops lacking saponin were ineffective. Systemic insulin absorption also was observed when Brij 78 or BL-9 was substituted for saponin in eye drops containing insulin. Nonanesthetized rats displayed lower initial D-glucose levels than anesthetized rats, and little hypoglycemic response to insulin eye drops could be observed, suggesting that counter-regulatory hormones could effectively counterbalance the influence of exogenous insulin on glycemic control. Streptozotocin-diabetic rats displayed elevated blood D-glucose values (greater than 400 mg/dl), and these values were decreased to 100-200 mg/dl after the administration of insulin in eye drop solutions containing saponin. The site of insulin absorption appears to be the nasolacrimal drainage system of the rat because administration of a solution containing insulin plus saponin directly into the punctum caused a rapid, significant decrease in blood D-glucose levels. The observation that insulin could be absorbed from the rat eye is consistent with the possibility that insulin eye drops containing an absorption-enhancing surfactant agent could be of potential benefit in the treatment of diabetes mellitus in humans.
authors.affiliation: Department of Pharmacology, University of Alabama, Birmingham 35294.
authors.forename: D J
authors.initials: DJ
authors.lastname: Pillion
authors.forename: J D
authors.initials: JD
authors.lastname: Bartlett
authors.forename: E
authors.initials: E
authors.lastname: Meezan
authors.forename: M
authors.initials: M
authors.lastname: Yang
authors.forename: R J
authors.initials: RJ
authors.lastname: Crain
authors.forename: W E
authors.initials: WE
authors.lastname: Grizzle
mesh_terms: D000042:Absorption; D000287:Administration, Topical; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D004337:Drug Carriers; D005123:Eye / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D009301:Nasolacrimal Duct / Q000000981:diagnostic imaging / Q000378:metabolism; D009883:Ophthalmic Solutions; D011859:Radiography; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin
chemical_list: D001786:Blood Glucose; D004337:Drug Carriers; D007328:Insulin; D009883:Ophthalmic Solutions; D013311:Streptozocin