{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T14:56:36Z","timestamp":1774364196249,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>GS\u20101427 is the oral prodrug of GS\u20101069518, an inhibitor of the \u03b14\u03b27 integrin, and is currently in development for the treatment of ulcerative colitis (UC). This first\u2010in\u2010human, phase 1, placebo\u2010controlled study evaluated the pharmacokinetics, safety, and tolerability of GS\u20101427 and GS\u20101069518 after single oral doses (20\u20101000 mg) or multiple once\u2010daily doses (20\u2010500 mg) of GS\u20101427 for 14 days. The bioavailability of tablet versus capsule formulations and the effect of food and an acid\u2010reducing agent (omeprazole) on exposure were also assessed. Overall, 148 healthy participants were enrolled, and 143 completed the study. GS\u20101427 was quickly converted to GS\u20101069518 during absorption. Upon repeated once\u2010daily dosing of GS\u20101427 under nonfasting conditions, steady\u2010state exposure to GS\u20101069518 was reached by day 5 with limited accumulation observed. At steady state, the median time to maximum concentration for GS\u20101069518 was 1\u20103\u00a0h and the mean terminal half\u2010life was 6.7\u201028.3\u00a0h. Bioavailability was lower in the tablet than in capsule formulation. Food intake and omeprazole coadministration reduced the exposure to GS\u20101069518 by approximately 20%\u201040%. Overall, 26\/122 participants (21.3%) who received GS\u20101427 and 8\/26 participants (30.1%) who received placebo experienced at least one treatment\u2010emergent adverse event (AE). Of the 148 participants, 10 (6.8%) experienced a treatment\u2010related AE, the most common being nausea (5\/148, 3.4%) and diarrhea (3\/148, 2.0%). All AEs were grade 1 in severity and no serious AEs or deaths were reported. The pharmacokinetics, safety, and tolerability results from this study support further evaluation of GS\u20101427 in a phase 2 trial in patients with UC.<\/jats:p>","DOI":"10.1002\/jcph.70177","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T11:56:27Z","timestamp":1773921387000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics, Safety, and Tolerability of GS\u20101427, an Oral Prodrug of a Potent and Selective \u03b14\u03b27 Integrin Inhibitor, in Healthy Participants"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9676-2001","authenticated-orcid":false,"given":"Jin","family":"Zhou","sequence":"first","affiliation":[{"name":"Gilead Sciences, Inc.  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