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S. H. Kim, R. J. Lutz, C. J. Galban, N. S. Wang, K. G. Csaky; Analysis of Drug Elimination Kinetics After Subconjunctival Injection Using Magnetic Resonance Imaging. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5785.
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© ARVO (1962-2015); The Authors (2016-present)
To study the elimination of model drugs gadolinium-diethylenetriaminopentaacetic acid (Gd-DTPA; 590 Da) and gadolinium-albumin (Gd-albumin; 67.4 kDa) after subconjunctival injection in vivo and post mortem using three-dimensional dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI).
Gd-DTPA and Gd-albumin were injected subconjunctivally into albino rabbits and scans acquired continuously for 2-5 hours to obtain real-time concentration levels of each contrast agent. The effect of injection volume was also studied by injecting 200 and 600 µl of Gd-DTPA. A simple pharmacokinetic model based on first-order clearance was formulated. The rate constants derived from in vivo and post mortem experiments were used to distinguish the effect of clearance by diffusion and clearance by blood and lymphatic flow.
The larger injection volume increased the retention time of Gd-DTPA in the subconjunctival tissue but did not alter the elimination rate both in vivo and post mortem. The clearance rate of Gd-DTPA was much more rapid in vivo than post mortem, while the clearance rate of Gd-albumin was similar for both in vivo and post mortem experiments. The clearance rate of Gd-DTPA was significantly faster than that of Gd-albumin both in vivo and post mortem.
Molecular weight/size may affect the clearance of drug molecules more significantly than injection volume. Small molecules may be more likely to be eliminated from the subconjunctival depot through blood and lymphatic vessels than larger molecules.
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