title: How can the bioavailability of timolol be enhanced? A pharmacokinetic pilot study of novel hydrogels.
abstract: BACKGROUND
  Carbomerbased hydrogels with timolol maleate (T-Gel) were chosen to study the vehicle effect on ocular bioavailability. Pharmacokinetic profiles of T-Gel 0.05% (0.05% timolol), T-Gel 0.025% (0.025% timolol) and commercial timolol ophthalmic solution (TOS 0.1%; 0.1% timolol) were determined and compared.
  
  
  METHODS
  A single dose was administered to rabbits' eyes. Timolol was determined by HPLC in aqueous humour, blood samples and washings of the ocular surface (as a measure of residence time). Sampling times were 0.5 h, 1 h and 4 h after instillation.
  
  
  RESULTS
  Concentration versus time curves (AUC) of timolol in aqueous humour demonstrate no significant differences between TOS 0.1% and T-Gel 0.025% (P = 0.19), whereas the difference between T-Gel 0.05% and TOS 0.1% is significant (P = 0.006); the AUC ratio of T-Gel 0.05%:TOS 0.1%:T-Gel 0.025% was 2.14:1:0.87. Timolol blood levels were highest with TOS 0.1% at every time point. Peak levels occurred after 0.5 h with all test products; the ratio of peak levels (Cmax) for T-Gel 0.05%:TOS 0.1%:T-Gel 0.025% was 0.55:1:0.17. Timolol was detected in the washings up to 1 h after instillation of test products; the highest levels were observed after T-Gel 0.05%.
  
  
  CONCLUSIONS
  The new vehicle obviously improves the bioavailability of topically applied timolol.
authors.affiliation: Klinik und Poliklinik für Augenheilkunde, Medizinische Hochschule Hannover, Germany.
authors.forename: N
authors.initials: N
authors.lastname: von der Ohe
authors.forename: M
authors.initials: M
authors.lastname: Stark
authors.forename: H
authors.initials: H
authors.lastname: Mayer
authors.forename: H
authors.initials: H
authors.lastname: Brewitt
mesh_terms: D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D001682:Biological Availability; D002682:Chinchilla; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D005782:Gels; D008297:Male; D009883:Ophthalmic Solutions; D010865:Pilot Projects; D011897:Random Allocation; D013999:Timolol / Q000493:pharmacokinetics*
chemical_list: D000319:Adrenergic beta-Antagonists; D004337:Drug Carriers; D005782:Gels; D009883:Ophthalmic Solutions; D013999:Timolol