Drug elimination kinetics following subconjunctival injection using dynamic contrast-enhanced magnetic resonance imaging

Purpose. To determine the elimination rates of subconjunctivally injected model drugs using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods. Gadolinium-diethylenetriaminopentaacetic acid (Gd-DTPA) and gadolinium-albumin (Gd-albumin) were injected in rabbits. Experiments were performed in vivo and post mortem and injection volumes of 200 and 600 mu l were administered. Signal intensity values from MR images were converted to concentration of contrast agent to determine the mass clearance rates from subconjunctival space. Results. Injection volume did not have a significant effect on clearance rate for both Gd-DTPA and Gd-albumin. The clearance rate of Gd-DTPA in vivo was about nine times faster than that post mortem. The in vivo and post mortem clearance rates of Gd-albumin were not significantly different. The in vivo half-life of Gd-DTPA was about 22 min while that of Gd-albumin was about 5.3 h. Conclusions. DCE-MRI was used to quantitatively compare the subconjunctival clearance rates of Gd-DTPA and Gd-albumin. Dynamic clearance mechanisms present in vivo significantly reduced the subconjunctival concentration of Gd-DTPA but not Gd-albumin. Lymphatic clearance does not seem to be as significant as clearance by blood, as evidenced by data from Gd-albumin injections. Larger injection volumes may allow for longer retention times and prolonged release of drug.