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M. D. de Smet, F. Aerts, B. Noppen, A. Gad El Kareen, J. Stassen; Determination of the Pharmacokinetics of Microplasmin in ex vivo Porcine Vitreous. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6237.
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Determine the kinetics of microplasmin enzyme activity in ex vivo vitreous.
Microplasmin’s enzymatic activity was determined in vitreous samples taken from porcine eyes at specific time points (0, 5, 15, 30, 60, 120 and 180 minutes) following intravitreal injection. Eyes were injected with 50, 125, 175, 250 µg of microplasmin in a citrate buffer. At each time point, residual enzymatic activity was determined on aliquots of vitreous by measuring the release of a chromophore p-nitroaniline (pNA) from the substrate Glu-Phe-Lys-pNAas on a spectrophotometer at 405 nm. Results were extrapolated to whole vitreous based on total vitreous weight.
Microplasmin enzymatic activity for a dose of 125µg reached the limit of detectability at 180 minutes. Microplasmin degradation most closely fits a second order kinetics with some prolongation in the terminal phase. The rate constant (k) is calculated to be about 1.5 mg-1min-1. Half life determined by the equation 1/(kA0) where A0 is the drug concentration being injected was 5 minutes for a dose of 125 µg.
Microplasmin activity in vitreous is dose dependent. The kinetics of degradation follow second order kinetic and is characterized by a short half life. Previous experiments have shown that the peak biologic activity as determined by the induction of a posterior vitreous detachment in this ex vivo model is achieved at 2 hours following microplasmin injection. This suggests that while the enzymatic activity is rapidly lost, biologic activity depends on the cumulated enzymatic effect or the induction of other endogenous pathways.
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