{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T09:26:17Z","timestamp":1784366777472,"version":"3.55.0"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2018,1,30]],"date-time":"2018-01-30T00:00:00Z","timestamp":1517270400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2018,1,30]],"date-time":"2018-01-30T00:00:00Z","timestamp":1517270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:p>\n                    Cerebral edema remains a significant cause of morbidity and mortality in patients with acute liver failure (ALF) and has been linked to elevated blood ammonia levels.\n                    <jats:sc>l<\/jats:sc>\n                    \u2010ornithine phenylacetate (OPA) may decrease ammonia by promoting its renal excretion as phenylacetylglutamine (PAGN), decreasing the risk of cerebral edema. We evaluated the safety, tolerability, and pharmacokinetics of OPA in patients with ALF and acute liver injury (ALI), including those with renal failure. Forty\u2010seven patients with ALI\/ALF and ammonia \u226560 \u03bcM were enrolled. Patients received OPA in a dose escalation scheme from 3.3 g every 24 hours to 10 g every 24 hours; 15 patients received 20 g every 24 hours throughout the infusion for up to 120 hours. Plasma phenylacetate (PA) concentrations were uniformly below target (&lt;75 \u03bcg\/mL) in those receiving 3.3 g every 24 hours (median [interquartile range] 5.0 [5.0] \u03bcg\/mL), and increased to target levels in all but one who received 20 g every 24 hours (150 [100] \u03bcg\/mL). Plasma [PAGN] increased, and conversion of PA to PAGN became saturated, with increasing OPA dose. Urinary PAGN clearance and creatinine clearance were linearly related (\n                    <jats:italic toggle=\"yes\">r<\/jats:italic>\n                    = 0.831,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.0001). Mean ammonia concentrations based on the area under the curve decreased to a greater extent in patients who received 20 g of OPA every 24 hours compared with those who received the maximal dose of 3.3 or 6.7 g every 24 hours (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.046 and 0.022, respectively). Of the reported serious adverse events (AEs), which included 11 deaths, none was attributable to study medication. The only nonserious AEs possibly related to study drug were headache and nausea\/vomiting.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    OPA was well\u2010tolerated in patients with ALI\/ALF, and no safety signals were identified. Target [PA] was achieved at infusion rates of 20 g every 24 hours, leading to ammonia excretion in urine as PAGN in proportion to renal function. Randomized, controlled studies of high\u2010dose OPA are needed to determine its use as an ammonia\u2010scavenging agent in patients with ALF. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2018;67:1003\u20131013)\n                  <\/jats:p>","DOI":"10.1002\/hep.29621","type":"journal-article","created":{"date-parts":[[2017,10,28]],"date-time":"2017-10-28T04:42:42Z","timestamp":1509165762000},"page":"1003-1013","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":35,"title":["Safety, tolerability, and pharmacokinetics of l\u2010ornithine phenylacetate in patients with acute liver injury\/failure and hyperammonemia"],"prefix":"10.1097","volume":"67","author":[{"given":"R. Todd","family":"Stravitz","sequence":"first","affiliation":[{"name":"Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Gottfried","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina,Charleston,SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Durkalski","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina,Charleston,SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Fontana","sequence":"additional","affiliation":[{"name":"University of Michigan,Ann Arbor,MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. James","family":"Hanje","sequence":"additional","affiliation":[{"name":"Ohio State University,Columbus,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Koch","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina,Charleston,SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilal","family":"Hameed","sequence":"additional","affiliation":[{"name":"University of California at San Francisco,San Francisco,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ganger","sequence":"additional","affiliation":[{"name":"Northwestern University,Chicago,IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram M.","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Emory University,Atlanta,GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stan","family":"Bukofzer","sequence":"additional","affiliation":[{"name":"Ocera Therapeutics,Durham,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Ravis","sequence":"additional","affiliation":[{"name":"Auburn University,Tuscaloosa,AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Clasen","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina,Charleston,SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Averell","family":"Sherker","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes,Digestive and Kidney Disease,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanna","family":"Little","sequence":"additional","affiliation":[{"name":"University of Texas,Southwestern Medical Center,Dallas,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2783-5441","authenticated-orcid":false,"given":"William M.","family":"Lee","sequence":"additional","affiliation":[{"name":"University of Texas,Southwestern Medical Center,Dallas,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Acute Liver Failure Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,1,30]]},"reference":[{"key":"hep29621-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"724","DOI":"10.7326\/M15-2211","article-title":"Outcomes in adults with acute liver failure between 1998 and 2013: an observational cohort study","volume":"164","year":"2016","journal-title":"Ann Intern Med"},{"key":"hep29621-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.cgh.2012.04.011","article-title":"Persistent hyperammonemia is associated with complications and poor outcomes in patients with acute liver failure","volume":"10","year":"2012","journal-title":"Clin 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