{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:34:24Z","timestamp":1791120864033,"version":"4.1.0"},"reference-count":8,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            IDX184 is a nucleotide prodrug designed to enhance formation in the liver of the active triphosphate of 2\u2032-methylguanosine (2\u2032-MeG), a potent and specific polymerase inhibitor of the hepatitis C virus (HCV). In the present study, single ascending oral doses of 5, 10, 25, 50, 75, and 100 mg IDX184 were administered sequentially to cohorts of 8 healthy subjects, randomized 6:2, active\/placebo. Plasma and urine pharmacokinetic sampling was performed over a period of 120 h after dosing. Upon absorption, IDX184 rapidly disappeared from plasma, with a mean half-life (\n            <jats:italic>t<\/jats:italic>\n            <jats:sub>1\/2<\/jats:sub>\n            ) of approximately 1 h, while plasma concentrations of 2\u2032-MeG gradually increased. Consistent with a liver-targeting approach, plasma exposure of IDX184 and 2\u2032-MeG was low and was also dose related: the mean maximum concentrations ranged from 1.1 to 17 ng\/ml for IDX184 and 1.7 to 19 ng\/ml for 2\u2032-MeG, and the respective mean total area under the curve ranged from 1.2 to 22.7 and 17.3 to 334 ng\u00b7h\/ml. Mean 2\u2032-MeG plasma concentrations 24 h after dosing were 0.6 to 3 ng\/ml for the 25- to 100-mg doses. Mean 2\u2032-MeG\n            <jats:italic>t<\/jats:italic>\n            <jats:sub>1\/2<\/jats:sub>\n            values ranged from 18 to 43 h for doses of 25 mg and above. Mean cumulative urine excretion was 0.2% and 12 to 20% of administered doses for the unchanged IDX184 and 2\u2032-MeG, respectively. IDX184 was safe and well tolerated; no serious adverse events (SAEs), dose-dependent adverse events (AEs), or dose-limiting toxicities were observed. The incidence of AEs and laboratory abnormalities was low and was similar among subjects receiving IDX184 or a placebo. All AEs were mild to moderate and resolved at the end of study. The favorable safety and pharmacokinetic profiles support further clinical evaluation of IDX184 in HCV-infected patients.\n          <\/jats:p>","DOI":"10.1128\/aac.01101-10","type":"journal-article","created":{"date-parts":[[2010,11,9]],"date-time":"2010-11-09T07:14:39Z","timestamp":1289286879000},"page":"76-81","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":61,"title":["Safety and Pharmacokinetics of IDX184, a Liver-Targeted Nucleotide Polymerase Inhibitor of Hepatitis C Virus, in Healthy Subjects"],"prefix":"10.1128","volume":"55","author":[{"given":"Xiao-Jian","family":"Zhou","sequence":"first","affiliation":[{"name":"Idenix Pharmaceuticals Inc., One Kendall Square, Suite B14104, Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Pietropaolo","sequence":"additional","affiliation":[{"name":"Idenix Pharmaceuticals Inc., One Kendall Square, Suite B14104, Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Idenix Pharmaceuticals Inc., One Kendall Square, Suite B14104, Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samina","family":"Khan","sequence":"additional","affiliation":[{"name":"Idenix Pharmaceuticals Inc., One Kendall Square, Suite B14104, Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sullivan-Bo\u0301lyai","sequence":"additional","affiliation":[{"name":"Idenix Pharmaceuticals Inc., One Kendall Square, Suite B14104, Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Mayers","sequence":"additional","affiliation":[{"name":"Idenix Pharmaceuticals Inc., One Kendall Square, Suite B14104, Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"S220","volume":"48","year":"2008","unstructured":"Cretton-Scott, E., C. Perigaud, S. Peyrottes, L. Licklider, M. Camire, M. Larsson, M. La Colla, E. Hildebrand, L. Lallos, J. Bilello, J. McCarville, M. Seifer, M. Liuzzi, C. Pierra, E. Badaroux, G. Gosselin, D. Surleraux, and D. N. Standring. 2008. In vitro antiviral activity and pharmacology of IDX184, a novel and potent inhibitor of HCV replication. J. Hepatol. 48(Suppl. 2):S220.","journal-title":"J. Hepatol."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020047"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(04)90096-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06102-5"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01317-07"},{"key":"e_1_3_2_7_2","first-page":"S30","volume":"48","year":"2008","unstructured":"Standring, D. N., R. Lanford, E. Cretton-Scott, L. Licklider, M. Larsson, C. Pierra, G. Gosselin, C. Perigaud, D. Surleraux, B. Mayes, A. Moussa, and J. Selden. 2008. Potent antiviral activity of second generation nucleoside inhibitors, IDX102 and IDX184, in HCV-infected chimpanzees. J. Hepatol. 48(Suppl. 2):S30.","journal-title":"J. Hepatol."},{"key":"e_1_3_2_8_2","first-page":"S37","volume":"50","year":"2009","unstructured":"Standring, D. N., R. Lanford, B. Li, R. J. Panzo, M. Seifer, M. Larsson, S. S. Good, and X. J. Zhou. 2009. Antiviral activity of the liver targeted nucleotide HCV polymerase inhibitor IDX184 correlates with trough serum levels of the nucleoside metabolite in HCV-infected chimpanzees. J. Hepatol. 50(Suppl. 1):S37.","journal-title":"J. Hepatol."},{"key":"e_1_3_2_9_2","unstructured":"World Health Organization. 2002. Hepatitis C. http:\/\/www.who.int\/csr\/disease\/hepatitis\/whocdscsrlyo2003\/en\/index.html. World Health Organization Geneva Switzerland."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01101-10","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01101-10","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T21:57:04Z","timestamp":1645480624000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01101-10"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1]]},"references-count":8,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,1]]}},"alternative-id":["10.1128\/AAC.01101-10"],"URL":"https:\/\/doi.org\/10.1128\/aac.01101-10","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,1]]},"assertion":[{"value":"2010-08-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-10-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}