title: Plasma timolol concentrations of timolol maleate: timolol gel-forming solution (TIMOPTIC-XE) once daily versus timolol maleate ophthalmic solution twice daily.
abstract: OBJECTIVE
  The objective of this study was to compare plasma concentrations of timolol following multiple dosing of the therapeutic regimens of timolol maleate ophthalmic gel-forming solution (Timolol GS; TIMOPTIC-XE) and timolol maleate ophthalmic solution. Timolol maleate ophthalmic gel-forming solution is also referred to as Timolol GS, i.e. gel-forming solution.
  
  
  METHODS
  This was a masked observer, two-period crossover study in six normal male subjects randomized to receive either Timolol GS, 0.5% (TIMOPTIC-XE,) once daily (0530 hours) or timolol maleate ophthalmic solution (0.5% TIMOPTIC) twice daily (0530 and 1730 hours) for 8 days, in both eyes. On Day 8, a blood sample was obtained prior to treatment, as well as 1, 2, 4, 8, 10, 12, 13, 14, 16, and 24 hours following the morning instillation. After a 7-day inter-period washout interval, subjects received the opposite treatment.
  
  
  RESULTS
  Timolol GS (TIMOPTIC-XE): Plasma concentrations of timolol rarely exceeded 0.375 ng/ml (the lower limit of assay quantification). For all subjects, peak plasma concentrations of timolol averaged <0.3 ng/ml within 4 hours after the last dose. The highest single observation was 0.49 ng/ml in one subject (at hour 2). Timolol solution: For all subjects, peak plasma concentrations of timolol averaged about 0.5 ng/ml and 0.3 ng/ml within 4 hours following the first and second dose, respectively, on Day 8. The highest single observation was 0.95 ng/ml in one subject (at hour 2).
  
  
  CONCLUSIONS
  The data suggest that there is less systemic exposure to timolol following once-daily therapy with Timolol GS 0.5% compared with twice daily therapy with timolol maleate ophthalmic solution 0.5%.
authors.affiliation: Merck Research Laboratories, West Point, PA, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Shedden
authors.forename: J
authors.initials: J
authors.lastname: Laurence
authors.forename: A
authors.initials: A
authors.lastname: Barrish
authors.forename: T V
authors.initials: TV
authors.lastname: Olah
mesh_terms: D000042:Absorption; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D001682:Biological Availability; D018592:Cross-Over Studies; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D005782:Gels; D006801:Humans; D008297:Male; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics; D013999:Timolol / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000319:Adrenergic beta-Antagonists; D005782:Gels; D009883:Ophthalmic Solutions; D013999:Timolol