Role of the Fc Region in the Vitreous Half- Life of Anti-VEGF Drugs

Cited 5 time in webofscience Cited 0 time in scopus
  • Hit : 262
  • Download : 162
DC FieldValueLanguage
dc.contributor.authorJoo, Kwangsicko
dc.contributor.authorPark, Sang Junko
dc.contributor.authorChoi, Yewonko
dc.contributor.authorLee, Jung-Eunko
dc.contributor.authorNa, Young Miko
dc.contributor.authorHong, Hye Kyoungko
dc.contributor.authorPark, Kyu Hyungko
dc.contributor.authorKim, Ho Minko
dc.contributor.authorChung, Jae-Yongko
dc.contributor.authorWoo, Se Joonko
dc.date.accessioned2017-10-23T02:00:35Z-
dc.date.available2017-10-23T02:00:35Z-
dc.date.created2017-10-10-
dc.date.created2017-10-10-
dc.date.issued2017-08-
dc.identifier.citationINVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v.58, no.10, pp.4261 - 4267-
dc.identifier.issn0146-0404-
dc.identifier.urihttp://hdl.handle.net/10203/226458-
dc.description.abstractPURPOSE. 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.languageEnglish-
dc.publisherASSOC RESEARCH VISION OPHTHALMOLOGY INC-
dc.subjectINTRAOCULAR PHARMACOKINETICS-
dc.subjectRABBIT MODEL-
dc.subjectRANIBIZUMAB-
dc.subjectBEVACIZUMAB-
dc.subjectRECEPTOR-
dc.subjectEYE-
dc.subjectAFLIBERCEPT-
dc.subjectSPECIFICITY-
dc.subjectSTABILITY-
dc.subjectDELIVERY-
dc.titleRole of the Fc Region in the Vitreous Half- Life of Anti-VEGF Drugs-
dc.typeArticle-
dc.identifier.wosid000410940400054-
dc.identifier.scopusid2-s2.0-85028586373-
dc.type.rimsART-
dc.citation.volume58-
dc.citation.issue10-
dc.citation.beginningpage4261-
dc.citation.endingpage4267-
dc.citation.publicationnameINVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE-
dc.identifier.doi10.1167/iovs.17-21813-
dc.contributor.localauthorKim, Ho Min-
dc.contributor.nonIdAuthorJoo, Kwangsic-
dc.contributor.nonIdAuthorPark, Sang Jun-
dc.contributor.nonIdAuthorChoi, Yewon-
dc.contributor.nonIdAuthorLee, Jung-Eun-
dc.contributor.nonIdAuthorNa, Young Mi-
dc.contributor.nonIdAuthorHong, Hye Kyoung-
dc.contributor.nonIdAuthorPark, Kyu Hyung-
dc.contributor.nonIdAuthorChung, Jae-Yong-
dc.contributor.nonIdAuthorWoo, Se Joon-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorVEGF-Trap-
dc.subject.keywordAuthorFcfVEGF-Trap-
dc.subject.keywordAuthorFc free VEGF-Trap-
dc.subject.keywordAuthorFc receptor-
dc.subject.keywordAuthorFc region-
dc.subject.keywordAuthoranti-VEGF-
dc.subject.keywordAuthorocular pharmacokinetics-
dc.subject.keywordPlusINTRAOCULAR PHARMACOKINETICS-
dc.subject.keywordPlusRABBIT MODEL-
dc.subject.keywordPlusRANIBIZUMAB-
dc.subject.keywordPlusBEVACIZUMAB-
dc.subject.keywordPlusRECEPTOR-
dc.subject.keywordPlusEYE-
dc.subject.keywordPlusAFLIBERCEPT-
dc.subject.keywordPlusSPECIFICITY-
dc.subject.keywordPlusSTABILITY-
dc.subject.keywordPlusDELIVERY-
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 5 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0