DC Field | Value | Language |
---|---|---|
dc.contributor.author | Joo, Kwangsic | ko |
dc.contributor.author | Park, Sang Jun | ko |
dc.contributor.author | Choi, Yewon | ko |
dc.contributor.author | Lee, Jung-Eun | ko |
dc.contributor.author | Na, Young Mi | ko |
dc.contributor.author | Hong, Hye Kyoung | ko |
dc.contributor.author | Park, Kyu Hyung | ko |
dc.contributor.author | Kim, Ho Min | ko |
dc.contributor.author | Chung, Jae-Yong | ko |
dc.contributor.author | Woo, Se Joon | ko |
dc.date.accessioned | 2017-10-23T02:00:35Z | - |
dc.date.available | 2017-10-23T02:00:35Z | - |
dc.date.created | 2017-10-10 | - |
dc.date.created | 2017-10-10 | - |
dc.date.issued | 2017-08 | - |
dc.identifier.citation | INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v.58, no.10, pp.4261 - 4267 | - |
dc.identifier.issn | 0146-0404 | - |
dc.identifier.uri | http://hdl.handle.net/10203/226458 | - |
dc.description.abstract | PURPOSE. To identify the role of the fragment crystallizable (Fc) region in determining intraocular protein drug pharmacokinetics. METHODS. We generated a new VEGF-Trap lacking the Fc region (FcfVEGF-Trap, MWt = 100 kDa) by replacing the Fc region of native VEGF-Trap (MWt = 145 kDa) with a dimerized coiled-coil domain. Forty-two rabbits were injected intravitreally with VEGF-Trap or FcfVEGF-Trap (n = 21 each) in one of the eyes, harvested at six time points (1 hour and 1, 2, 4, 14, and 30 days after injections). VEGF-Trap and FcfVEGF-Trap concentrations in the vitreous, aqueous humor, and retina/choroid were measured, and drug pharmacokinetic properties were analyzed. RESULTS. In all three ocular compartments, the maximal concentrations for both FcfVEGF-Trap and VEGF-Trap were observed at 1 hour after injection. Half-lives of FcfVEGF-Trap in the vitreous and retina/choroid (145.02 and 102.12 hours, respectively) were 1.39 and 2.30 times longer than those of VEGF-Trap (103.99 and 44.42 hours, respectively). Total exposure of the aqueous humor and retina/choroid to FcfVEGF-Trap was 13.2% and 39% of the vitreous exposure, respectively, whereas VEGF-Trap concentrations were 25.2% and 26.2%, indicating that FcfVEGF-Trap shows a preference for posterior distribution and elimination. CONCLUSIONS. FcfVEGF-Trap, despite its lower molecular weight, showed longer half-lives in vitreous and retina/choroid than VEGF-Trap did, suggesting that Fc receptors in ocular tissues contribute to anti-VEGF drug elimination. Truncation or mutation of the Fc region can prolong the intraocular residence time of VEGF-Trap and possibly reduce the number of VEGF-Trap injections required in clinical practice. | - |
dc.language | English | - |
dc.publisher | ASSOC RESEARCH VISION OPHTHALMOLOGY INC | - |
dc.subject | INTRAOCULAR PHARMACOKINETICS | - |
dc.subject | RABBIT MODEL | - |
dc.subject | RANIBIZUMAB | - |
dc.subject | BEVACIZUMAB | - |
dc.subject | RECEPTOR | - |
dc.subject | EYE | - |
dc.subject | AFLIBERCEPT | - |
dc.subject | SPECIFICITY | - |
dc.subject | STABILITY | - |
dc.subject | DELIVERY | - |
dc.title | Role of the Fc Region in the Vitreous Half- Life of Anti-VEGF Drugs | - |
dc.type | Article | - |
dc.identifier.wosid | 000410940400054 | - |
dc.identifier.scopusid | 2-s2.0-85028586373 | - |
dc.type.rims | ART | - |
dc.citation.volume | 58 | - |
dc.citation.issue | 10 | - |
dc.citation.beginningpage | 4261 | - |
dc.citation.endingpage | 4267 | - |
dc.citation.publicationname | INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE | - |
dc.identifier.doi | 10.1167/iovs.17-21813 | - |
dc.contributor.localauthor | Kim, Ho Min | - |
dc.contributor.nonIdAuthor | Joo, Kwangsic | - |
dc.contributor.nonIdAuthor | Park, Sang Jun | - |
dc.contributor.nonIdAuthor | Choi, Yewon | - |
dc.contributor.nonIdAuthor | Lee, Jung-Eun | - |
dc.contributor.nonIdAuthor | Na, Young Mi | - |
dc.contributor.nonIdAuthor | Hong, Hye Kyoung | - |
dc.contributor.nonIdAuthor | Park, Kyu Hyung | - |
dc.contributor.nonIdAuthor | Chung, Jae-Yong | - |
dc.contributor.nonIdAuthor | Woo, Se Joon | - |
dc.description.isOpenAccess | Y | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | VEGF-Trap | - |
dc.subject.keywordAuthor | FcfVEGF-Trap | - |
dc.subject.keywordAuthor | Fc free VEGF-Trap | - |
dc.subject.keywordAuthor | Fc receptor | - |
dc.subject.keywordAuthor | Fc region | - |
dc.subject.keywordAuthor | anti-VEGF | - |
dc.subject.keywordAuthor | ocular pharmacokinetics | - |
dc.subject.keywordPlus | INTRAOCULAR PHARMACOKINETICS | - |
dc.subject.keywordPlus | RABBIT MODEL | - |
dc.subject.keywordPlus | RANIBIZUMAB | - |
dc.subject.keywordPlus | BEVACIZUMAB | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | EYE | - |
dc.subject.keywordPlus | AFLIBERCEPT | - |
dc.subject.keywordPlus | SPECIFICITY | - |
dc.subject.keywordPlus | STABILITY | - |
dc.subject.keywordPlus | DELIVERY | - |
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