{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:02:12Z","timestamp":1791414132424,"version":"4.3.3"},"reference-count":14,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"National Natural Science Foundation Incubation Program of The Second Hospital of Anhui Medical University","award":["No.2022GMFY08"],"award-info":[{"award-number":["No.2022GMFY08"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      HRS-8427 is a novel parenteral siderophore cephalosporin that shows potent efficacy against various gram-negative bacteria, including carbapenem-resistant strains,\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and in preclinical models of infection. It underwent a single-dose ascending study (400\u20136,000 mg) and a multiple-dose ascending study (1,000\u20133,000 mg q8h) in healthy Chinese adults to evaluate pharmacokinetics (PK), safety, and tolerability. A total of 62 treatment-emergent adverse events (TEAEs) occurred in 29 subjects during the treatment period, resulting in a TEAE incidence of 36.7% (29\/79). There were no serious adverse events (AEs) observed in either study. Three subjects (one in the 2,000 mg single-dose group and two in the 3,000 mg multi-dose group) withdrew from the trial due to AEs. Approximately dose-proportional increases in the maximum plasma concentration (\n                      <jats:italic toggle=\"yes\">C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ) and the area under the concentration-time curve (AUC) were observed across the single-dose range of 400\u20136,000 mg, although the drug exposure increased slightly less than the dose. The mean plasma half-life of HRS-8427 was 3.89 to 4.28 h. HRS-8427 was primarily excreted unchanged in the urine (62.13% to 71.12% of the dose). There was minimal systemic accumulation of\n                      <jats:italic toggle=\"yes\">C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      and AUC by dosing q8h, and the PK of HRS-8427 did not change with multiple dosing. This study indicates that both single and multiple intravenous doses of HRS-8427, up to 6,000 mg and 2,000 mg, respectively, are well tolerated in healthy subjects and show generally linear pharmacokinetics at doses up to 6,000 mg.\n                    <\/jats:p>\n                    <jats:p>\n                      This study is registered with the Chinese Clinical Trial registry as\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.chictr.org.cn\/showprojEN.html?proj=176382\" xlink:type=\"simple\">ChiCTR2200062570<\/jats:ext-link>\n                      , and ClinicalTrials.gov as\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT07070375\" xlink:type=\"simple\">NCT07070375<\/jats:ext-link>\n                      ,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT06144060\" xlink:type=\"simple\">NCT06144060<\/jats:ext-link>\n                      ,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT06569056\" xlink:type=\"simple\">NCT06569056<\/jats:ext-link>\n                      ,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT06841731\" xlink:type=\"simple\">NCT06841731<\/jats:ext-link>\n                      ,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT07049562\" xlink:type=\"simple\">NCT07049562<\/jats:ext-link>\n                      ,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT07049107\" xlink:type=\"simple\">NCT07049107<\/jats:ext-link>\n                      , and\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT07073157\" xlink:type=\"simple\">NCT07073157<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00694-25","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T14:38:42Z","timestamp":1772548722000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetics, safety, and tolerability of HRS-8427, a novel anti-carbapenem-resistant cephalosporin, in healthy subjects"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8423-505X","authenticated-orcid":true,"given":"Tengrui","family":"Yin","sequence":"first","affiliation":[{"name":"Jiangsu Hengrui Medicine Co. Ltd.","place":["Lianyungang, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8615-8666","authenticated-orcid":true,"given":"Biao","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University","place":["Hefei, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Hengrui Medicine Co. Ltd.","place":["Lianyungang, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Jiangsu Hengrui Medicine Co. Ltd.","place":["Lianyungang, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijue","family":"Wu","sequence":"additional","affiliation":[{"name":"Jiangsu Hengrui Medicine Co. Ltd.","place":["Lianyungang, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Jiangsu Hengrui Medicine Co. Ltd.","place":["Lianyungang, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5851-4856","authenticated-orcid":true,"given":"Yuanyuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Jiangsu Hengrui Medicine Co. Ltd.","place":["Lianyungang, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4809-7601","authenticated-orcid":false,"given":"Wei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University","place":["Hefei, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00876-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s41182-023-00524-w"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-022-07436-w"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12111590"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01580-4"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-020-00286-6"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S347343"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02163-17"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-015-0347-x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199325020-00002"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02134-12"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-024-01171-9"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2019.34.e328"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2019.34.e319"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00694-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00694-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T13:01:44Z","timestamp":1775048504000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00694-25"}},"subtitle":[],"editor":[{"given":"James E.","family":"Leggett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":14,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,1]]}},"alternative-id":["10.1128\/aac.00694-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.00694-25","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,1]]},"assertion":[{"value":"2025-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00694-25"}}