title: Timolol LA: a double-masked, active-controlled, randomized, crossover, comfort, ocular safety, and systemic bioavailability study in healthy volunteers.
abstract: OBJECTIVE
  A new formulation of timolol with sorbic acid, timolol-LA (TLA) (Istaloldagger), has been developed which increases its ocular bioavailability. In the present study, we desired to evaluate the ocular comfort and systemic bioavailability of TLA in healthy volunteers in comparison to standard timolol maleate ophthalmic solution (TIM).
  
  
  METHODS
  This study was a randomized, double-masked, active-controlled, crossover evaluation of 0.5% TLA and 0.5% TIM, bid, in 12 normal healthy volunteers. Visits were at Days 0, 1, 2, 4 and 8 in each period, and there was a minimum 7 day interperiod washout.
  
  
  RESULTS
  At all three post-dosing evaluation times (Day 1: Peak, Day 8: Trough, and Day 8: Peak), the 95% confidence interval for the difference between TLA and TIM was not more than 0.37 ng/mL. After administration of TLA, there was a greater incidence of burning/stinging and tearing, but not foreign body sensation, relative to TIM. In general, most symptoms were mild in intensity, and no subject discontinued treatment due to ocular discomfort. Both treatments decreased IOP to a similar level.
  
  
  CONCLUSIONS
  TLA was relatively comfortable, with a safety profile consistent with further clinical development, and, with bid dosing (exaggerated [2X] that anticipated for clinical use), had a systemic bioavailability similar to that of TIM 0.5%, bid. The incidence of burning and stinging was higher with TLA than with TIM, although reports were mild in severity and did not result in any patient discontin uations. Although the results are of interest, further evaluation in a larger trial may be warranted.
authors.affiliation: Charlotte, NC, USA.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Mundorf
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ogawa
authors.forename: Noritsugu
authors.initials: N
authors.lastname: Inui
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Naka
authors.forename: Gary D
authors.initials: GD
authors.lastname: Novack
authors.forename: R Stephens
authors.initials: RS
authors.lastname: Crockett
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000494:pharmacology; D000328:Adult; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009883:Ophthalmic Solutions; D013011:Sorbic Acid; D013999:Timolol / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D009883:Ophthalmic Solutions; D013999:Timolol; D013011:Sorbic Acid