Improved systemic safety and risk–benefit ratio of topical 0.1% timolol hydrogel compared with 0.5% timolol aqueous solution in the treatment of glaucoma
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Many ophthalmologists routinely administer subconjunctival antibiotics at the end of cataract surgery for prophylaxis against bacterial endophthalmitis. Additionally they use acetazolamide and/or timolol to control intraocular pressure in the first 24-hour postoperative period. An animal study was undertaken to learn whether treatment with the aqueous humor suppressants, acetazolamide, and timolol prolongs the concentrations of antibiotics in the aqueous humor after subconjunctival administration of the antibiotic. Treatment with acetazolamide significantly increased concentrations of piperacillin; it had less consistent effects on tobramycin levels. Timolol treatment did not produce increased piperacillin concentrations at six hours; however, concentrations at 12 and 24 hours were significantly higher than in the controls. Timolol treatment increased tobramycin concentrations only at six hours. The combined use of timolol and acetazolamide produced significantly higher concentrations of piperacillin, but not of tobramycin.
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The distribution of radioactivity in 15 ocular and extraocular tissues or fluids of the rabbit after ocular instillation and intravenous injection of 100 microL of 14C-labeled timolol solution (1.5%) was studied by liquid scintillation counting (LSC). The drug was distributed rapidly among the tissues examined after both routes of administration. Levels of radioactivity were considerably greater in ocular tissues after instillation as compared with intravenous injection, whereas in extraocular tissues the levels were similar after both routes of administration. Using the same experimental protocol, aqueous humor and serum levels of unchanged timolol were measured by gas liquid chromatography. Comparisons with LSC studies indicated that, following ocular instillation, only unchanged timolol was present in aqueous humor, whereas both timolol and metabolites were present in serum. After intravenous administration, timolol was rapidly metabolized and metabolites appeared in the serum and aqueous humor.
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It is assumed that S-timolol can produce more severe systemic adverse reactions than R-timolol. The aim of this study was to estimate the intraocular pressure-lowering effect of RS-timolol in comparison to R-timolol and S-timolol in water-loaded rabbits.Ocular hypertension was provoked in rabbits by orogastric water loading. Topical administration of one of three timolol solutions: 0.85%, RS-timolol, or 3% R-timolol, or 0.5% S-timolol was performed to the right eyes 40 min before starting the water loading procedure. Left eyes served as a control group. Intraocular pressure was measured before and 30, 60, 90, 120 min after the water loading.Intraocular pressure-lowering effect of all three timolol solutions was comparable.RS-timolol can be effective for lowering intraocular pressure in rabbits.
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