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

S. J. Park, J. Oh, Y. K. Kim, J. H. Park, J. Y. Park, H. K. Hong, K. H. Park, J. E. Lee, H. M. Kim, J. Y. Chung, S. J. Woo

Research output: Contribution to journalArticle

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Abstract

PurposeTo determine intraocular pharmacokinetic properties of intravitreally injected vascular endothelial growth factor (VEGF)-Trap in a rabbit model.MethodsVEGF-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.ResultsMaximum 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.ConclusionThe 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.

Original languageEnglish
Pages (from-to)561-568
Number of pages8
JournalEye (Basingstoke)
Volume29
Issue number4
DOIs
StatePublished - 20 Apr 2015

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Vascular Endothelial Growth Factor A
Pharmacokinetics
Rabbits
Choroid
Aqueous Humor
Vitreous Body
Half-Life
Retina
Vascular Endothelial Growth Factor C
Injections
Area Under Curve
Enzyme-Linked Immunosorbent Assay

Cite this

Park, S. J. ; Oh, J. ; Kim, Y. K. ; Park, J. H. ; Park, J. Y. ; Hong, H. K. ; Park, K. H. ; Lee, J. E. ; Kim, H. M. ; Chung, J. Y. ; Woo, S. J. / Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-Trap in a rabbit model. In: Eye (Basingstoke). 2015 ; Vol. 29, No. 4. pp. 561-568.
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title = "Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-Trap in a rabbit model",
abstract = "PurposeTo determine intraocular pharmacokinetic properties of intravitreally injected vascular endothelial growth factor (VEGF)-Trap in a rabbit model.MethodsVEGF-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.ResultsMaximum 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.ConclusionThe 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.",
author = "Park, {S. J.} and J. Oh and Kim, {Y. K.} and Park, {J. H.} and Park, {J. Y.} and Hong, {H. K.} and Park, {K. H.} and Lee, {J. E.} and Kim, {H. M.} and Chung, {J. Y.} and Woo, {S. J.}",
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Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-Trap in a rabbit model. / Park, S. J.; Oh, J.; Kim, Y. K.; Park, J. H.; Park, J. Y.; Hong, H. K.; Park, K. H.; Lee, J. E.; Kim, H. M.; Chung, J. Y.; Woo, S. J.

In: Eye (Basingstoke), Vol. 29, No. 4, 20.04.2015, p. 561-568.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-Trap in a rabbit model

AU - Park, S. J.

AU - Oh, J.

AU - Kim, Y. K.

AU - Park, J. H.

AU - Park, J. Y.

AU - Hong, H. K.

AU - Park, K. H.

AU - Lee, J. E.

AU - Kim, H. M.

AU - Chung, J. Y.

AU - Woo, S. J.

PY - 2015/4/20

Y1 - 2015/4/20

N2 - PurposeTo determine intraocular pharmacokinetic properties of intravitreally injected vascular endothelial growth factor (VEGF)-Trap in a rabbit model.MethodsVEGF-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.ResultsMaximum 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.ConclusionThe 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.

AB - PurposeTo determine intraocular pharmacokinetic properties of intravitreally injected vascular endothelial growth factor (VEGF)-Trap in a rabbit model.MethodsVEGF-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.ResultsMaximum 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.ConclusionThe 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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U2 - 10.1038/eye.2014.329

DO - 10.1038/eye.2014.329

M3 - Article

C2 - 25592118

AN - SCOPUS:84927922537

VL - 29

SP - 561

EP - 568

JO - Eye (Basingstoke)

JF - Eye (Basingstoke)

SN - 0950-222X

IS - 4

ER -