{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:15:45Z","timestamp":1791814545371,"version":"4.3.4"},"reference-count":48,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Neovascular age\u2010related macular degeneration (nAMD) and diabetic macular edema (DME) can cause substantial vision loss. The 2\u2010mg drug product of aflibercept (AFL\u20102)\u2014an anti\u2010vascular endothelial growth factor agent\u2014has established efficacy and safety in both diseases. In pivotal trials, a high\u2010dose drug product (AFL\u2010HD) using a formulation distinct from AFL\u20102 and delivering 8\u2010mg aflibercept every 12 or 16\u2009weeks (following initial monthly dosing) provided visual gains non\u2010inferior to AFL\u20102 administered every 8\u2009weeks (following initial monthly dosing) and comparable safety with fewer injections over 96\u2009weeks. Free and bound aflibercept concentrations in plasma from 2744 participants in 16 clinical trials where aflibercept was administered intravitreally, subcutaneously, or intravenously were analyzed by population pharmacokinetic modeling. A semi\u2010mechanistic model described the release of free aflibercept from the eye and its target\u2010mediated elimination from plasma. The evaluated covariates (weight, age, sex, albumin, disease, racial classification, Japanese origin, renal and hepatic functions) resulted in only small numerical differences in systemic exposure. Ocular clearance (\n                    <jats:italic>Q<\/jats:italic>\n                    <jats:sub>E<\/jats:sub>\n                    ; characterizing the bidirectional transfer of free aflibercept between the eye and central compartment) was comparable across both diseases after adjusting for an age\u2010dependent decrease. The change in drug product, and not just the dose increase, was responsible for a 39.4% slower\n                    <jats:italic>Q<\/jats:italic>\n                    <jats:sub>E<\/jats:sub>\n                    and extended exposure in the ocular space for AFL\u2010HD versus AFL\u20102. The median ocular concentrations of free aflibercept predicted at the end of the 8\u2010week dosing interval for AFL\u20102 were typically reached 14\u2009weeks after AFL\u2010HD injections, versus 9\u20139.5\u2009weeks if\n                    <jats:italic>Q<\/jats:italic>\n                    <jats:sub>E<\/jats:sub>\n                    was identical for both drug products.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70287","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T10:20:54Z","timestamp":1782901254000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrated Population Pharmacokinetic Analysis of Intravitreal Aflibercept Drug Products"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2326-3335","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Bihorel","sequence":"first","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6715-8260","authenticated-orcid":false,"given":"Joannellyn","family":"Chiu","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0195-0855","authenticated-orcid":false,"given":"Jason","family":"Chittenden","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  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