Drug elimination kinetics following subconjunctival injection using dynamic contrast-enhanced magnetic resonance imaging.
OBJECTIVE
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 microl 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.
Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland, USA. kimstep@mail.nih.gov
Stephanie H
SH
Kim
Karl G
KG
Csaky
Nam Sun
NS
Wang
Robert J
RJ
Lutz
D000418:Albumins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D003228:Conjunctiva / Q000098:blood supply / Q000378:metabolism*; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D021621:Imaging, Three-Dimensional; D007267:Injections; D008208:Lymphatic System / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008657:Metabolic Clearance Rate; D008970:Molecular Weight; D011817:Rabbits; D012815:Signal Processing, Computer-Assisted
D000418:Albumins; D003287:Contrast Media; D019786:Gadolinium DTPA