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JD Dickinson, TL LeVatte, ML Archibald, A Tan, BC Chauhan; Human Vitreous and Plasma Concentration of Topically and Orally Administered Timolol . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4075.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the posterior vitreous and plasma concentrations of topically and orally administered timolol. Knowledge of posterior segment drug penetration is important in ascertaining potential vasoactive or neuroprotective drug effects. Methods: Nineteen eyes of 19 patients undergoing pars plana vitrectomy for macular hole or premacular fibrosis were randomized to either timolol 0.5% drops twice daily (10 patients) or timolol 10 mg orally twice daily (9 patients) for one week prior to surgery. Patients with prior history of ocular surgery, uveitis, corneal disease, diabetes or retinal detachment were excluded. These exclusion criteria were applied to ensure that drug delivery to the posterior segment was not enhanced by a compromised blood retinal barrier. An undiluted sample of posterior vitreous was obtained at the beginning of a three port vitrectomy. Plasma was obtained simultaneously at the time of the surgical procedure. The samples were stored at -70 ºC. Samples were later extracted and drug concentrations determined using High Performance Liquid Chromatography (HPLC). Analysis was carried out using a Supelcosil LC-8 column and UV detection at a wavelength of 294 nm. Results: There was no detectable timolol in the vitreous of any patient. Plasma levels of timolol were present in all patients who received systemic timolol (mean 0.123 µM, range 0.048 to 0.181µM). Plasma levels were not detected for any of the topically administered timolol patients. Conclusion: Topically and orally administered timolol used in standard clinical doses does not reach the posterior vitreous at concentrations measurable by our HPLC technique.
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