Plasma timolol concentrations of timolol maleate: timolol gel-forming solution (TIMOPTIC-XE) once daily versus timolol maleate ophthalmic solution twice daily.
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%.
Shedden
A H
AH
Merck Research Laboratories, West Point, PA, USA.
Laurence
J
J
Barrish
A
A
Olah
T V
TV
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*
D000319:Adrenergic beta-Antagonists; D005782:Gels; D009883:Ophthalmic Solutions; D013999:Timolol