{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:19:01Z","timestamp":1789953541215,"version":"4.0.1"},"reference-count":14,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,3,16]],"date-time":"2013-03-16T00:00:00Z","timestamp":1363392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Glycerol tri\u2010(4\u2010phenylbutyrate) (glycerol phenylbutyrate, GPB, HPN\u2010100) mediates waste nitrogen excretion through conjugation with glutamine to form phenylacetylglutamine which is excreted in urine. This pilot study was performed to assess tolerability and effect on venous ammonia concentration in patients with cirrhosis and hepatic encephalopathy (HE). Patients underwent one week of 6\u2009mL (6.6\u2009g) twice daily (BID). GPB dosing followed by 3 weeks of 9 mL (9.9\u2009g) BID dosing and underwent repeated blood sampling for ammonia concentration and pharmacokinetics. Fifteen patients were enrolled. Ammonia concentrations were lowest after overnight fast and increased post\u2010prandially. Fasting ammonia concentrations were lower on GPB compared to baseline, with a decrease on the eighth day of 6\u2009mL BID dosing to 45.4 (27.9)\u2009\u00b5mol\/L (ULN \u223c48 \u00b5mol\/L) (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05). Nine milliliters BID yielded similar lowering but was associated with more adverse events and higher phenylacetate (PAA) plasma concentrations (PAA\u2009C<jats:sub>max<\/jats:sub> of 144 [125] vs. 292 [224]\u2009\u00b5g\/mL on 6 and 9\u2009mL, respectively). GPB dosed at 6\u2009mL BID lowered fasting ammonia levels in cirrhotic patients with HE as compared with baseline, was better tolerated than 9\u2009mL BID, and is appropriate for further evaluation in patients with cirrhosis and episodic HE.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cpdd.18","type":"journal-article","created":{"date-parts":[[2013,3,17]],"date-time":"2013-03-17T02:37:57Z","timestamp":1363487877000},"page":"278-284","source":"Crossref","is-referenced-by-count":25,"title":["Glycerol Phenylbutyrate in Patients With Cirrhosis and Episodic Hepatic Encephalopathy: A Pilot Study of Safety and Effect on Venous Ammonia Concentration"],"prefix":"10.1002","volume":"2","author":[{"given":"Marwan","family":"Ghabril","sequence":"first","affiliation":[{"name":"Indiana University School of Medicine Indianapolis, IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor A.","family":"Zupanets","sequence":"additional","affiliation":[{"name":"National University of Pharmacy Kharkiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Vierling","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine Houston, TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parvez","family":"Mantry","sequence":"additional","affiliation":[{"name":"Liver Institute at Methodist Dallas Medical Center Dallas, TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don","family":"Rockey","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern, Dallas, TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Wolf","sequence":"additional","affiliation":[{"name":"New York Medical College Valhalla, NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"O'Shea","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Cleveland, OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Dickinson","sequence":"additional","affiliation":[{"name":"Hyperion Therapeutics, Inc. South San Francisco, CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Gillaspy","sequence":"additional","affiliation":[{"name":"Hyperion Therapeutics, Inc. South San Francisco, CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Norris","sequence":"additional","affiliation":[{"name":"Hyperion Therapeutics, Inc. South San Francisco, CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dion F.","family":"Coakley","sequence":"additional","affiliation":[{"name":"Hyperion Therapeutics, Inc. South San Francisco, CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoud","family":"Mokhtarani","sequence":"additional","affiliation":[{"name":"Hyperion Therapeutics, Inc. South San Francisco, CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce F.","family":"Scharschmidt","sequence":"additional","affiliation":[{"name":"Hyperion Therapeutics, Inc. South San Francisco, CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-984575"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-984574"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-984576"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107410"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(02)01477-8"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907893"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(10)60197-3"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.03.014"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23589"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.04.013"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26058"},{"key":"e_1_2_6_13_1","first-page":"1690","article-title":"A phase I and pharmacokinetic study of intravenous phenylacetate in patients with cancer","volume":"54","author":"Thibault A","year":"1994","journal-title":"Cancer Res."},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19950615)75:12<2932::AID-CNCR2820751221>3.0.CO;2-P"},{"key":"e_1_2_6_15_1","first-page":"248A","article-title":"Randomized, controlled, double\u2010blind study of glycerol phenylbutyrate in patients with cirrhosis and episodic hepatic encephalopathy","volume":"56","author":"Rockey D","year":"2012","journal-title":"Hepatology."}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpdd.18","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.18","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T18:18:48Z","timestamp":1696616328000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.18"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,16]]},"references-count":14,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,7]]}},"alternative-id":["10.1002\/cpdd.18"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.18","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,16]]}}}