title: Pharmacokinetics and tolerability (Study 1) with particular reference to ocular safety (Study 2) of tiotropium Respimat soft mist inhaler: findings from two dose-ranging studies in healthy men.
abstract: Data are presented from two randomized, double-blind, placebo-controlled studies in which the tolerability of tiotropium Respimat Soft MistTM Inhaler (SMI), a new-generation, propellant-free device for use in COPD, and the ocular safety oftiotropium were examined. In Study 1, 36 healthy males received tiotropium 8, 16, or 32 microg (n = 9/dose) or placebo (n = 3/dose level), administered once daily via Respimat SMI for 14 days. Safety and pharmacokinetics were evaluated. In Study 2, 48 healthy males received tiotropium 0.02, 0.04, 0.08, 0.16, 0.28, or 0.40 microg (n = 6/dose) or placebo (n = 2/dose level), applied as two drops to one eye (the highest dose was a significant multiple of a percentage of the proposed Respimat SMI clinical dose that could be inadvertently deposited in the eye). Ocular parameters were measured over 24 hours. Tiotropium Respimat SMI at doses up to 32 microg was well tolerated in Study 1; typical dose-dependent anticholinergic adverse events of mild-to-moderate intensity were observed. In Study 2, ocular tiotropium administration did not affect pupil diameter, pupillary reflex, intraocular pressure, or accommodation. Tiotropium Respimat SMI was well tolerated. Inadvertent ocular exposure to tiotropium up to 0.40 g is unlikely to result in ocular adverse effects.
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Strasse 173,55216 Ingelheim, Germany. Ulrich.feifel@ing.boehringer-ingelheim.com
authors.forename: Ulrich
authors.initials: U
authors.lastname: Feifel
authors.forename: Gudrun
authors.initials: G
authors.lastname: Wallenstein
authors.forename: Karl-Ludwig
authors.initials: KL
authors.lastname: Rominger
authors.forename: Dirk
authors.initials: D
authors.lastname: Trommeshauser
authors.forename: Juliane
authors.initials: J
authors.lastname: Platz
mesh_terms: D000328:Adult; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004311:Double-Blind Method; D004867:Equipment Design; D005123:Eye / Q000187:drug effects; D006801:Humans; D008297:Male; D009330:Nebulizers and Vaporizers; D009883:Ophthalmic Solutions; D012602:Scopolamine Derivatives / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000069447:Tiotropium Bromide; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents; D009883:Ophthalmic Solutions; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide