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K. Hosseini, D. Matsushima, J. Johnson, G. Widera, K. Nyam, L. Kim, Y. Xu, Y. Yao, M. Cormier; Intravitreal, Subconjunctival, and Intravenous Delivery of Dexamethasone Disodium Phosphate in Rabbits; A Pharmacokinetic Study. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1825. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To compare pharmacokinetics of dexamethasone disodium phosphate following intravitreal, subconjunctival, or intravenous injection in rabbits.
Pharmacokinetics of dexamethasone phosphate (DP), a water soluble prodrug of dexamethasone, following intravenous (IV), subconjunctival (SC), and intravitreal (IVT) administration in rabbits at low (25 µg/kg) and high (250 µg/kg) doses were investigated. The concentrations of DP and dexamethasone were examined in plasma at different time points using a LC/MS/MS method with a limit of detection of 0.5 ng/ml.
Data demonstrated a rapid conversion of the prodrug to the drug with all routes of administration. IV and SC delivery resulted in peak plasma concentrations after only 5 and 12-25 min, respectively, followed by rapid plasma elimination. IVT delivery exhibited a depot effect with very low plasma levels of dexamethasone throughout the 24-hour time course.
These results emphasize the need for IVT administration of dexamethasone to minimize systemic exposure.
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