How can the bioavailability of timolol be enhanced? A pharmacokinetic pilot study of novel hydrogels.
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.
von der Ohe
N
N
Klinik und Poliklinik für Augenheilkunde, Medizinische Hochschule Hannover, Germany.
Stark
M
M
Mayer
H
H
Brewitt
H
H
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*
D000319:Adrenergic beta-Antagonists; D004337:Drug Carriers; D005782:Gels; D009883:Ophthalmic Solutions; D013999:Timolol