Introduction
Timolol is a beta receptor antagonist used in equine medicine to decrease intra ocular pressure. Despite anecdotal reports on decreased aerobic performance in humans using timolol eye-drops, neither the pharmacokinetics nor the systemic exposure to timolol after administration as eye-drops have been investigated in horses. The potential misuse as a performance lowering or heart rate lowering agent warrant further interest.
Material and methods
Timolol was administered to two standardbred horses in a two treatment cross over design with one week wash-out between treatment: intravenously (30 mg/500 kg) and topically in the conjunctival sack (10 mg in 0.2 mL volume). Plasma and urine samples were then collected as follows: Plasma was sampled pre-administration and then after 2, 5, 10, 15, 30, 45 min and 1, 1,5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 h (seven days). Urine was sampled via catheterization pre-administration and approximately 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 h (seven days) post administration. The same sampling protocol was applied independent on route of administration.
The samples were then analysed using ultra-high performance liquid chromatography - tandem mass spectrometry (UHPLC-MS/MS).
Results
In plasma, timolol was detected for 8 h and 12 h after intravenous administration and 1.5 h and 3 h after topical administration. In urine, timolol was detected for 48 h and 56 h after intravenous administration and 3 h after topical administration.
Discussion
The results from this pilot study suggest that timolol is possible to control and detection times for clinical doses should be possible to decide on for interested regulatory bodies. However, data from additional horses are requested.