{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T15:53:53Z","timestamp":1777910033948,"version":"3.51.4"},"reference-count":33,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"published-print":{"date-parts":[[2024,10,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>\n                      Emerging data suggest that acetaminophen lowers intraocular pressure (IOP) and has the potential to be repurposed as pharmacotherapy to treat open-angle glaucoma. However, pharmacokinetic data are lacking. This study aims to describe the pharmacokinetics of topical acetaminophen and its metabolite [\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      -arachidonoylaminophenol (AM404)] when administered individually and in combination, and to determine its effect on IOP in the ocular normotensive adult New Zealand White Rabbit (NZWR).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>A randomized control trial was conducted using topical 1% acetaminophen and 1% AM404. The study was divided into two sub-studies using both paired-eye and two-eye designs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The mean [95% confidence interval of the mean (95% CI)] concentration of acetaminophen detected in the aqueous humor (AH) was 4.09 ppm (3.18\u20135.00) at 2 h and 0.92 ppm (0.60\u20131.24) at 4 h after an immediate dose of topical acetaminophen. The integral IOP, defined as the integral of IOP change from baseline over time, was \u22125.1 mmHg\u22c5h (95% CI: \u221210 to 0.41) for control,\u22127.5 mmHg\u22c5h (95% CI: \u221214 to \u22121.1) for half-hourly acetaminophen, and \u22124.4 mmHg\u22c5h (95% CI: \u221214 to 5.5) for hourly acetaminophen over a 4-h period. When comparing topical acetaminophen with AM404 dosed half-hourly over a 4-h period, the integral IOP was \u22122.3 mmHg\u22c5h (95% CI: \u22125.9 to 1.3) for control,\u22122.0 mmHg\u22c5h (95% CI: \u22125.6 to 1.7) for AM404, \u22121.7 mmHg\u22c5h (95% CI: \u22124.5 to 1.2) for acetaminophen, and \u22123.2 mmHg\u22c5h (95% CI: \u22125.4 to \u22120.96) for acetaminophen\/AM404 combined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Acetaminophen, but not its metabolite AM404, penetrated the multilayered cornea via passive diffusion in a dose-dependent fashion. There was a nonsignificant tendency to cause a lowering of IOP over the 4-h dosing period with higher AH concentrations of acetaminophen. Topical AM404 did not show a significant IOP-lowering effect.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2024.0020","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T05:19:37Z","timestamp":1716787177000},"page":"513-523","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["The Ocular Penetration and Intraocular Pressure Lowering Effect of Topical Acetaminophen in the New Zealand White Rabbit"],"prefix":"10.1177","volume":"40","author":[{"given":"Sean G.","family":"Anderson","sequence":"first","affiliation":[{"name":"Division of Pharmacology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Meyer","sequence":"additional","affiliation":[{"name":"Division of Ophthalmology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric H.","family":"Decloedt","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S87988"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S38473"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40123-019-00222-z"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16257-0"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2016-EGSguideline.003"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.12.015"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501489200"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)01297-1"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5329.1094"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00786-X"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3458.2006.00250.x"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(24)37121-6"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011058411804"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/APO.0000000000000181"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13346-020-00843-z"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2710.2009.01143.x"},{"issue":"8","key":"e_1_3_6_18_2","first-page":"1186","article-title":"Statistical analysis of multi-eye data in ophthalmic research","volume":"26","author":"Ray WA","year":"1985","unstructured":"Ray WA, , O\u2019Day DM. 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