Pharmacokinetics and safety of intravitreally delivered etanercept.
BACKGROUND
The anti-inflammatory drug etanercept may be an effective therapeutic agent in diabetic retinopathy. In order to further evaluate its potential, the pharmacokinetics and safety of this drug after intravitreal delivery were investigated.


METHODS
After intravitreal administration of etanercept in rabbits, clinical examination, electroretinography (ERG), visually evoked potentials (VEP) and histology were evaluated. The pharmacokinetics and distribution of etanercept were analyzed using fluorescence-coupled protein at 0, 2, 4, and 8 weeks after injection in vitreous, retina, and choroid.


RESULTS
No adverse effects and signs of toxicity were found. Etanercept showed peak concentrations after 4 weeks in the retina and choroid.


CONCLUSIONS
Intravitreally delivered etanercept is safe and results in high concentrations in the retina and choroid over a long period of time.
Fauser
Sascha
S
Abteilung für Netzhaut- und Glaskörperchirurgie des Zentrums für Augenheilkunde und Zentrum für Molekulare Medizin (ZMMK), Universität zu Köln, Joseph-Stelzmann-Strasse 9, 50931 Cologne, Germany. sfauser@hgmp.mrc.ac.uk
Kalbacher
Hubert
H
Alteheld
Nils
N
Koizumi
Kan
K
Krohne
Tim U
TU
Joussen
Antonia M
AM
D000818:Animals; D002829:Choroid / Q000187:drug effects / Q000378:metabolism*; D004596:Electroretinography; D000068800:Etanercept; D005074:Evoked Potentials, Visual; D007074:Immunoglobulin G / Q000378:metabolism* / Q000633:toxicity; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000633:toxicity; D007267:Injections; D008297:Male; D011817:Rabbits; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D014018:Tissue Distribution; D014822:Vitreous Body / Q000378:metabolism*
D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept