2015
DOI: 10.1002/jps.24480
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The PK-Eye: A Novel In Vitro Ocular Flow Model for Use in Preclinical Drug Development

Abstract: A 2-compartment in vitro eye flow model has been developed to estimate ocular drug clearance by the anterior aqueous outflow pathway. The model is designed to accelerate the development of longer-acting ophthalmic therapeutics. Dye studies show aqueous flow is necessary for a molecule injected into the vitreous cavity to clear from the model. The clearance times of proteins can be estimated by collecting the aqueous outflow, which was first conducted with bevacizumab using phosphate-buffered saline in the vitr… Show more

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Cited by 63 publications
(94 citation statements)
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References 125 publications
(210 reference statements)
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“…Prior to loading bevacizumab into the NIPAAM gel, three doses of bevacizumab ( Figure 2 ) were evaluated using the PK‐Eye to determine clearance times. The PK‐Eye is a two compartment, aqueous outflow model scaled to the eye that has been shown to estimate the human clearance times of therapeutic proteins from the back of the eye . Novel formulations of protein therapeutics and long acting implants can be optimized and in vitro in vivo correlations elucidated .…”
Section: Resultsmentioning
confidence: 99%
See 3 more Smart Citations
“…Prior to loading bevacizumab into the NIPAAM gel, three doses of bevacizumab ( Figure 2 ) were evaluated using the PK‐Eye to determine clearance times. The PK‐Eye is a two compartment, aqueous outflow model scaled to the eye that has been shown to estimate the human clearance times of therapeutic proteins from the back of the eye . Novel formulations of protein therapeutics and long acting implants can be optimized and in vitro in vivo correlations elucidated .…”
Section: Resultsmentioning
confidence: 99%
“…The percentage of the protein that cleared from the posterior cavity of the PK‐Eye using PBS by day 9 was 95.1 ± 3.1 and 83.0 ± 7.9% for the 2.5 and 5.0 mg doses respectively. For comparison, a t 1/2 of 1.2 ± 0.1 d and a protein release of 93.6 ± 7.6% was observed for the clearance of the clinical dose (1.25 mg) of bevacizumab with PBS in the PK‐Eye …”
Section: Resultsmentioning
confidence: 99%
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“…For example, there are marked differences in vitreous clearance rate between small lipophilic molecules and larger biologics such as proteins (hours vs days to weeks). [25] Compared to the anterior route, posterior clearance of larger drugs is negligible due to limited permeability of the blood-ocular barriers. [23] Moreover, while small drugs permeate through the ocular barriers more readily than larger drugs, their intravitreal clearance is also much more rapid due to their lower molecular weight allowing rapid vitreous diffusion.…”
Section: Primary Physiological Barriersmentioning
confidence: 99%