{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T01:17:09Z","timestamp":1789089429035,"version":"build-2803163510"},"reference-count":22,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,10,8]],"date-time":"2023-10-08T00:00:00Z","timestamp":1696723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["aspenjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Parenter Enteral Nutr"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Enteral drug therapy is challenging in short bowel syndrome with intestinal failure (SBS\u2010IF) because of unpredictable absorption. SEFA\u20106179 is an enterally administered medium\u2010chain fatty acid analogue under development for intestinal failure\u2013associated liver disease. We investigate the pharmacokinetics of two SEFA\u20106179 formulations in two large\u2010animal models of SBS\u2010IF, including a new pseudojejunostomy model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty Yucatan minipigs were obtained. Half underwent pre\u2010resection pharmacokinetic study with single\u2010dose SEFA\u20106179 administration. All minipigs then underwent 90% jejunoileal resection, with either a jejunoileal anastomosis or bypass of the intraperitoneal colon with anastomosis just proximal to the rectum (pseudojejunostomy). On postoperative day 3, a single\u2010dose pharmacokinetic study was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both SBS\u2010IF models were well tolerated. Compared with the jejunoileal anastomosis minipigs, pseudojejunostomy minipigs had a more severe malabsorptive phenotype with weight loss by postoperative day 4 (+0.1 vs \u22120.9\u2009kg, <jats:italic>P<\/jats:italic>\u2009=\u20090.03) and liquid diarrhea (Bristol 5 vs Bristol 7, <jats:italic>P<\/jats:italic>\u2009=\u20090.0007). Compared with pre\u2010resection minipigs, both jejunoileal and pseudojejunostomy minipigs had lower total plasma exposure of SEFA\u20106179 measured by area under the curve (jejunoileal: 37% less, <jats:italic>P<\/jats:italic>\u2009=\u20090.049; pseudojejunostomy: 74% less, <jats:italic>P<\/jats:italic>\u2009=\u20090.0001). Peak plasma concentration was also lower in the pseudojejunostomy group compared with pre\u2010resection (65% less, <jats:italic>P<\/jats:italic>\u2009=\u20090.04), but not lower in the jejunoileal group (<jats:italic>P<\/jats:italic>\u2009=\u20090.47).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In two SBS\u2010IF minipig models, SEFA\u20106179 had substantially decreased absorption compared with pre\u2010resection minipigs. Dose optimization for different intestinal anatomy and function may be required. We describe a new SBS\u2010IF pseudojejunostomy model that may improve the translation of preclinical research to patients with SBS\u2010IF who have enterostomies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jpen.2563","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T21:28:06Z","timestamp":1695158886000},"page":"1028-1037","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Absorption of an engineered medium\u2010chain fatty acid analogue in two short bowel syndrome minipig models"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4591-9371","authenticated-orcid":false,"given":"Scott C.","family":"Fligor","sequence":"first","affiliation":[{"name":"Vascular Biology Program, Department of Surgery Boston Children's Hospital Boston Massachusetts USA"},{"name":"Harvard Medical School Boston Massachusetts 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Centers for Clinical and Translational Research Boston Children's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5143-9879","authenticated-orcid":false,"given":"Mikayla","family":"Quigley","sequence":"additional","affiliation":[{"name":"Vascular Biology Program, Department of Surgery Boston Children's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0658-9835","authenticated-orcid":false,"given":"Sarah","family":"Carbeau","sequence":"additional","affiliation":[{"name":"Vascular Biology Program, Department of Surgery Boston Children's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Nedder","sequence":"additional","affiliation":[{"name":"Animal Resources Children's Hospital Boston Children's Hospital Boston Massachusetts 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