Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-Trap in a rabbit model

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Purpose To determine intraocular pharmacokinetic properties of intravitreally injected vascular endothelial growth factor (VEGF)-Trap in a rabbit model. Methods VEGF-Trap was intravitreally injected in 18 rabbit eyes. Eyes were enucleated 1 h and 1, 2, 5, 14, and 30 days after injections and immediately frozen at - 80 degrees C. Concentration of VEGF-Trap in vitreous, aqueous humor, and retina/choroid was determined using an indirect enzyme-linked immunosorbent assay and analyzed to obtain pharmacokinetic properties. Results Maximum concentration of VEGF-Trap was achieved at 1 h in all three tissues. A one-compartment model of distribution was selected as the final model for all tissues studied. Estimated half-life of VEGF-Trap in vitreous, aqueous humor, and retinal/choroid was 87.1, 36.8, and 35.0 h, respectively, and estimated mean residence time was 125.7, 53.1, and 50.5 h, respectively. Area under the curve from time 0 to the end point was 10009.8, 3945.1, and 1189.3, respectively. Total exposure of the aqueous humor and retina/choroid to VEGF-Trap was 39.4% and 11.9% of vitreous exposure, respectively. Conclusion The vitreous half-life of VEGF-Trap is 3.63 days. This is shorter than that of bevacizumab 6.99 days) and longer than that of ranibizumab (2.51 days), as shown in studies using the same experimental settings. The concentration of VEGF-Trap peaked at 1 h after injections in all eye tissues studied.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2015-04
Language
English
Article Type
Article
Keywords

DIABETIC MACULAR EDEMA; VEGF-TRAP; AFLIBERCEPT INJECTION; RANIBIZUMAB; DEGENERATION; EYES; BEVACIZUMAB; RECEPTOR

Citation

EYE, v.29, no.4, pp.561 - 568

ISSN
0950-222X
DOI
10.1038/eye.2014.329
URI
http://hdl.handle.net/10203/201000
Appears in Collection
MSE-Journal Papers(저널논문)
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