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. 2015 Apr;29(4):561-8.
doi: 10.1038/eye.2014.329. Epub 2015 Jan 16.

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

S J Park  1 , J Oh  2 , Y-K Kim  1 , J H Park  1 , J Y Park  1 , H K Hong  1 , K H Park  1 , J-E Lee  3 , H M Kim  3 , J Y Chung  2 , S J Woo  1
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Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-Trap in a rabbit model

S J Park et al. Eye (Lond). 2015 Apr.

Abstract

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 °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.

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Figures

Figure 1
Figure 1
Sequence of two vascular endothelial growth factor-Traps (VEGF-Traps). VBS indicates the VEGF-Trap sequence used in the present study and Patent indicates VEGF-Trap-Eye (Aflibercept, Eylea) sequence from the patent (Regeneron). The discordance in sequences of the two proteins occurred within 5.3% (25 out of 476 amino acids). VBS is a sequence constructed by the laboratory named ‘Vascular Biology and Stem Cell (VBS) laboratory' in the Korea Advanced Institute of Science and Technology (KAIST).
Figure 2
Figure 2
Basic goodness-of-fit plot for the one-compartment model. (a and b) Vitreous, (c and d) aqueous humor, and (e and f) retina/choroid.
Figure 3
Figure 3
VEGF-Trap concentration in the eye of rabbits. Points represent the observed concentrations and lines represent the estimated concentrations determined by the one-compartmental model.
See this image and copyright information in PMC

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