title: Plasma levels and systemic safety of 0.1% unpreserved timolol maleate gel, 0.5% timolol aqueous solution and 0.5% timolol maleate gel.
abstract: OBJECTIVE
  To compare systemic absorption of three formulations of timolol eye drops: 0.1% timolol maleate gel, 0.5% timolol aqueous solution, and 0.5% timolol maleate gel.
  
  
  METHODS
  This was a double cross-over phase I study. Cross-over 1: two weeks of 0.1% timolol gel once daily, followed by a 3-week wash-out period and then two weeks of 0.5% timolol aqueous solution twice a day (group 1) or the reverse (group 2). Cross-over 2: two weeks of 0.1% timolol gel once daily, followed by a 3-week wash-out period, and then two weeks of 0.5% timolol gel once daily (group 3) or the reverse (group 4). Subjects underwent tonometry, blood sampling, and heart rate and blood pressure assessments (during bicycle exercise and head-up tilt tests) before and after instillation at the beginning and end of each treatment period.
  
  
  RESULTS
  Forty-three healthy volunteers were randomized: 11 subjects in groups 1, 2, and 3, and 10 subjects in group 4. Areas under the concentration-time curve (AUC) values after administration of timolol 0.5% formulations were 15- to 38-fold higher than those seen after administration of timolol 0.1% gel. Maximum timolol concentrations after instillation of 0.1% gel are reduced by almost 90% compared to concentrations obtained after both 0.5% aqueous solution and 0.5% gel instillation. The AUC between 0 and 12 h post-administration were also reduced by up to 93 to 98%.
  
  
  CONCLUSIONS
  After treatment with a timolol 0.1% gel formulation, systemic concentrations found were considerably lower than after administration of timolol 0.5% gel or in aqueous solution.
authors: Service d'Ophtalmologie, Hôpital Gabriel-Montpied, rue Montalembert, 63003 Clermont-Ferrand cedex, France.
authors: N
authors: N
authors: Bonnin
authors: H
authors: H
authors: Nezzar
authors: C
authors: C
authors: Dubray
authors: D
authors: D
authors: Renault
authors: C
authors: C
authors: Olmiere
authors: F
authors: F
authors: Chiambaretta
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005782:Gels; D006257:Head / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D009994:Osmolar Concentration; D011309:Preservation, Biological; D012996:Solutions / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D018667:Tilt-Table Test; D013999:Timolol / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood* / Q000493:pharmacokinetics; D014867:Water; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D005782:Gels; D009883:Ophthalmic Solutions; D012996:Solutions; D014867:Water; D013999:Timolol