{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:53:00Z","timestamp":1791175980178,"version":"4.1.0"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To evaluate aqueous humor concentrations of nepafenac following topical administration of 0.3% and 0.1% formulations, to assess the influence of timing of instillation on intraocular exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Aqueous humor samples collected during anterior segment surgery were analyzed. Nepafenac concentrations were quantified in 151 samples (0.3% instilled once daily: n = 73; 0.1% instilled three times daily: n = 78). Amfenac was quantified only in the nepafenac 0.3% group (n = 73), owing to the stepwise validation of the analytical method (see Limitations). Due to right-skewed distributions, concentrations were summarized as median (IQR) and geometric mean with 95% confidence intervals Mann\u2013Whitney U test and Spearman\u2019s rank correlation coefficient were applied. Postoperative optical coherence tomography was performed at 1, 2, and 3 months to assess the occurrence of Irvine\u2013Gass syndrome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Geometric mean nepafenac concentrations were 22.13 nM (95% CI 15.85\u201330.91) for 0.3% and 21.73 nM (95% CI 13.29\u201335.53) for 0.1% (p = 0.319). Within the 0.1% group, instillation timing significantly influenced concentrations (p &amp;lt; 0.001), with markedly higher levels approximately 30\u201360 min after instillation compared with the 10\u201312 h subgroup. Amfenac correlated with nepafenac (\u03c1 = 0.56, p &amp;lt; 0.001). No cases of clinically evident Irvine\u2013Gass syndrome were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>No cases of clinically evident Irvine\u2013Gass syndrome were observed; however, the study was not powered or designed to assess clinical efficacy. Timing of instillation is a major determinant of aqueous humor nepafenac concentrations. Preoperative instillation shortly before surgery may optimize intraoperative drug availability and support maintenance of mydriasis. Standardized sampling is essential for robust pharmacokinetic comparisons.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmolb.2026.1913752","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:32:43Z","timestamp":1791174763000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Instillation timing as the main determinant of aqueous humor nepafenac exposure"],"prefix":"10.3389","volume":"13","author":[{"given":"Angelo","family":"Macri","sequence":"first","affiliation":[{"name":"IRCCS AOM Azienda Ospedaliera Metropolitana - Ospedale Policlinico San Martino","place":["Genoa, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Salis","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES), University of Genoa","place":["Genoa, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Tarallo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa","place":["Genoa, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Iester","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa","place":["Genoa, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Damonte","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES), University of Genoa","place":["Genoa, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mattioli","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (DIMI), Pharmacology and Toxicology Unit, University of Genoa","place":["Genoa, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1177\/11206721251317652","article-title":"Nepafenac role in macular swelling prevention and in visual outcome after cataract surgery - a systematic review and meta-analysis","volume":"35","author":"Almasri","year":"2025","journal-title":"Eur. 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