{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:01:20Z","timestamp":1786122080490,"version":"build-2736575974"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"\n Background<\/jats:title>\n \n Meropenem-vaborbactam is a fixed-dose \u03b2-lactam\/\u03b2-lactamase inhibitor combination active against carbapenem-resistant\n Enterobacterales<\/jats:italic>\n (CRE), especially\n Klebsiella pneumoniae<\/jats:italic>\n carbapenemase (KPC)-producing CRE. This study evaluated its pharmacokinetics (PK), safety, and tolerability in Chinese participants, and performed population pharmacokinetics\/pharmacodynamics (PK\/PD) analysis using\n in vitro<\/jats:italic>\n data to assess the suitability of the standard dosing regimen for treating CRE infections in China.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n This single-center, open-label study included 20 healthy participants divided into two groups receiving meropenem-vaborbactam (1:1) at 1\u00a0g\/1\u00a0g or 2\u00a0g\/2\u00a0g via 3-h infusion. Plasma and urine concentrations of meropenem, its open-ring metabolite, and vaborbactam were analyzed using a validated liquid chromatography-tandem mass spectrometry method. PK analysis was conducted using WinNonlin. Monte Carlo simulations were used to evaluate the 1\u00a0g\/1\u00a0g and 2\u00a0g\/2\u00a0g regimens administered every 8\u00a0h as 3-h intravenous infusions. For the standard 2\u00a0g\/2\u00a0g regimen, the impact of extending the infusion duration from 3 to 4\u00a0h was further evaluated based on the FDA-recommended PK\/PD target.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Plasma concentrations of meropenem, its open-ring metabolite, and vaborbactam peaked immediately after infusion, with rapid distribution and elimination. Exposure increased proportionally with dose, and almost no accumulation was observed after repeated 8-hourly dosing. Most meropenem (68.5%\u201377.0%) and nearly all vaborbactam were excreted unchanged in urine. Both single and multiple doses were well tolerated, with no severe or serious adverse events. In addition, PK\/PD analysis showed that, for CRE isolates, the standard 2\u00a0g\/2\u00a0g every 8\u00a0h regimen with a 3-h intravenous infusion achieved \u226590% probability of target attainment for meropenem (45%\n f<\/jats:italic>\n T &gt; MIC) at MIC values up to 8\u00a0mg\/L. The corresponding cumulative fraction of response ranged from 98.67 to 100% across ESBL-producing and KPC-producing\n Enterobacterales<\/jats:italic>\n , including\n bla<\/jats:italic>\n KPC<\/jats:sub>\n variants resistant to ceftazidime-avibactam.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The standard meropenem-vaborbactam regimen (2\u00a0g\/2\u00a0g every 8\u00a0h, 3-h intravenous infusion) demonstrated favorable PK and safety profiles, with PK\/PD analyses supporting the appropriateness of the standard regimen in Chinese participants, consistent with global findings. These results provide PK\/PD support for the standard regimen and warrant further evaluation in Chinese patients with CRE infections.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphar.2026.1887991","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T08:38:22Z","timestamp":1786091902000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics, safety and population pharmacokinetics\/pharmacodynamics analysis of meropenem-vaborbactam in Chinese healthy participants"],"prefix":"10.3389","volume":"17","author":[{"given":"Wanzhen","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Antibiotics, Key Laboratory of Clinical Pharmacology of Antibiotics, National Clinical Research Center for Aging and Medicine, Joint Laboratory of Hospital & Enterprise for Pathogen Diagnosis of Drug-resistant Bacterial Infections and Innovative Drug R&D, Huashan Hospital, Fudan University","place":["Shanghai, China"]},{"name":"Professional Technical Service Platform for Comprehensive Preclinical Pharmacodynamic Evaluation and Clinical Translation of Antibacterial Agents, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Wei","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Research Center, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengting","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Key Laboratory of Clinical Pharmacology of Antibiotics, National Clinical Research Center for Aging and Medicine, Joint Laboratory of Hospital & Enterprise for Pathogen Diagnosis of Drug-resistant Bacterial Infections and Innovative Drug R&D, Huashan Hospital, Fudan University","place":["Shanghai, China"]},{"name":"Professional Technical Service Platform for Comprehensive Preclinical Pharmacodynamic Evaluation and Clinical Translation of Antibacterial Agents, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofen","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Key Laboratory of Clinical Pharmacology of Antibiotics, National Clinical Research Center for Aging and Medicine, Joint Laboratory of Hospital & Enterprise for Pathogen Diagnosis of Drug-resistant Bacterial Infections and Innovative Drug R&D, Huashan Hospital, Fudan University","place":["Shanghai, China"]},{"name":"Professional Technical Service Platform for Comprehensive Preclinical Pharmacodynamic Evaluation and Clinical Translation of Antibacterial Agents, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beining","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Key Laboratory of Clinical Pharmacology of Antibiotics, National Clinical Research Center for Aging and Medicine, Joint Laboratory of Hospital & Enterprise for Pathogen Diagnosis of Drug-resistant Bacterial Infections and Innovative Drug R&D, Huashan Hospital, Fudan University","place":["Shanghai, China"]},{"name":"Professional Technical Service Platform for Comprehensive Preclinical Pharmacodynamic Evaluation and Clinical Translation of Antibacterial Agents, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuancheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Research Center, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"SciClone Pharmaceuticals (China) Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Guan","sequence":"additional","affiliation":[{"name":"SciClone Pharmaceuticals (China) Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Shen","sequence":"additional","affiliation":[{"name":"SciClone Pharmaceuticals (China) Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Wang","sequence":"additional","affiliation":[{"name":"SciClone Pharmaceuticals (China) Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanyang","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Research Center, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Key Laboratory of Clinical Pharmacology of Antibiotics, National Clinical Research Center for Aging and Medicine, Joint Laboratory of Hospital & Enterprise for Pathogen Diagnosis of Drug-resistant Bacterial Infections and Innovative Drug R&D, Huashan Hospital, Fudan University","place":["Shanghai, China"]},{"name":"Professional Technical Service Platform for Comprehensive Preclinical Pharmacodynamic Evaluation and Clinical Translation of Antibacterial Agents, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Key Laboratory of Clinical Pharmacology of Antibiotics, National Clinical Research Center for Aging and Medicine, Joint Laboratory of Hospital & Enterprise for Pathogen Diagnosis of Drug-resistant Bacterial Infections and Innovative Drug R&D, Huashan Hospital, Fudan University","place":["Shanghai, China"]},{"name":"Professional Technical Service Platform for Comprehensive Preclinical Pharmacodynamic Evaluation and Clinical Translation of Antibacterial Agents, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Hu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Research Center, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Key Laboratory of Clinical Pharmacology of Antibiotics, National Clinical Research Center for Aging and Medicine, Joint Laboratory of Hospital & Enterprise for Pathogen Diagnosis of Drug-resistant Bacterial Infections and Innovative Drug R&D, Huashan Hospital, Fudan University","place":["Shanghai, China"]},{"name":"Professional Technical Service Platform for Comprehensive Preclinical Pharmacodynamic Evaluation and Clinical Translation of Antibacterial Agents, Huashan Hospital, Fudan University","place":["Shanghai, China"]},{"name":"Clinical Pharmacology Research Center, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Wu","sequence":"additional","affiliation":[{"name":"Professional Technical Service Platform for Comprehensive Preclinical Pharmacodynamic Evaluation and Clinical Translation of Antibacterial Agents, Huashan Hospital, Fudan University","place":["Shanghai, China"]},{"name":"Clinical Pharmacology Research Center, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1007\/s00134-020-06050-1","article-title":"Antimicrobial therapeutic drug monitoring in critically ill adult patients: a position paper","volume":"46","author":"Abdul-Aziz","year":"2020","journal-title":"Intensive Care Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e02313","DOI":"10.1128\/AAC.02313-19","article-title":"Meropenem-vaborbactam versus ceftazidime-avibactam for treatment of carbapenem-resistant enterobacteriaceae infections","volume":"64","author":"Ackley","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e01551-18","DOI":"10.1128\/AAC.01551-18","article-title":"Meropenem-vaborbactam as salvage therapy for ceftazidime-avibactam-resistant Klebsiella pneumoniae bacteremia and abscess in a liver transplant recipient","volume":"63","author":"Athans","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"B4","doi-asserted-by":"publisher","first-page":"220119","DOI":"10.1183\/16000617.0119-2022","article-title":"New antibiotics for Gram-negative pneumonia","volume":"31","author":"Bassetti","year":"2022","journal-title":"Eur. Respir. Rev."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e0213021","DOI":"10.1128\/aac.02130-21","article-title":"Pharmacokinetic-pharmacodynamic target attainment analyses as support for meropenem-vaborbactam dosing regimens and susceptibility breakpoints","volume":"66","author":"Bhavnani","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"B6","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.clinthera.2020.01.021","article-title":"Assessment of meropenem and vaborbactam room temperature and refrigerated stability in polyvinyl chloride bags and elastomeric devices","volume":"42","author":"Chen","year":"2020","journal-title":"Clin. Ther."},{"key":"B7","article-title":"Performance Standards for Antimicrobial Susceptibility Testing","year":"2026"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e0000823","DOI":"10.1128\/cmr.00008-23","article-title":"Klebsiella pneumoniae carbapenemase variants: the new threat to global public health","volume":"36","author":"Ding","year":"2023","journal-title":"Clin. Microbiol. Rev."},{"key":"B9","doi-asserted-by":"publisher","first-page":"106992","DOI":"10.1016\/j.ijantimicag.2023.106992","article-title":"A descriptive pharmacokinetic\/pharmacodynamic analysis of continuous infusion meropenem\/vaborbactam in the treatment of critically ill patients with documented KPC-producing Klebsiella pneumoniae ventilator-associated pneumonia","volume":"62","author":"Gatti","year":"2023","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2586","DOI":"10.1093\/jac\/dkae261","article-title":"Biliary pharmacokinetic\/pharmacodynamic analysis of continuous infusion meropenem\/vaborbactam in a case series of orthotopic liver transplant recipients","volume":"79","author":"Gatti","year":"2024","journal-title":"J. Antimicrob. Chemother."},{"key":"B11","doi-asserted-by":"publisher","first-page":"6326","DOI":"10.1128\/aac.00568-16","article-title":"Phase 1 study of the safety, tolerability, and pharmacokinetics of the \u03b2-Lactamase inhibitor vaborbactam (RPX7009) in healthy adult subjects","volume":"60","author":"Griffith","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e01659-18","DOI":"10.1128\/AAC.01659-18","article-title":"Pharmacokinetics\/Pharmacodynamics of vaborbactam, a novel beta-lactamase inhibitor, in combination with meropenem","volume":"63","author":"Griffith","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"B13","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s13054-019-2378-9","article-title":"Optimization of the treatment with beta-lactam antibiotics in critically ill patients-guidelines from the French Society of Pharmacology and Therapeutics (Soci\u00e9t\u00e9 Fran\u00e7aise de Pharmacologie et Th\u00e9rapeutique-SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Soci\u00e9t\u00e9 Fran\u00e7aise d'Anesth\u00e9sie et R\u00e9animation-SFAR)","volume":"23","author":"Guilhaumou","year":"2019","journal-title":"Crit. Care"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e0160225","DOI":"10.1128\/aac.01602-25","article-title":"Comparative outcomes of ceftazidime-avibactam versus meropenem-vaborbactam for KPC-producing Enterobacterales infections","volume":"70","author":"Karaba","year":"2026","journal-title":"Antimicrob. Agents Chemother."},{"key":"B15","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1001\/jama.2018.0438","article-title":"Effect of meropenem-vaborbactam vs piperacillin-tazobactam on clinical cure or improvement and microbial eradication in complicated urinary tract infection: the TANGO I randomized clinical trial","volume":"319","author":"Kaye","year":"2018","journal-title":"JAMA"},{"key":"B16","doi-asserted-by":"publisher","first-page":"ofad327","DOI":"10.1093\/ofid\/ofad327","article-title":"Clinical characteristics and outcome of Ceftazidime\/avibactam-resistant Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae infections: a retrospective, observational, 2-Center clinical study","volume":"10","author":"Oliva","year":"2023","journal-title":"Open Forum Infect. Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e02228-17","DOI":"10.1128\/AAC.02228-17","article-title":"Phase 1 study of the safety, tolerability, and pharmacokinetics of vaborbactam and meropenem alone and in combination following single and multiple doses in healthy adult subjects","volume":"62","author":"Rubino","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e0260620","DOI":"10.1128\/aac.02606-20","article-title":"Population pharmacokinetics of meropenem and vaborbactam based on data from noninfected subjects and infected patients","volume":"65","author":"Trang","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"B19","doi-asserted-by":"publisher","first-page":"dlac022","DOI":"10.1093\/jacamr\/dlac022","article-title":"Compassionate use of meropenem\/vaborbactam for infections caused by KPC-producing klebsiella pneumoniae: a multicentre study","volume":"4","author":"Tumbarello","year":"2022","journal-title":"JAC Antimicrob. Resist"},{"key":"B20","doi-asserted-by":"publisher","first-page":"ofae273","DOI":"10.1093\/ofid\/ofae273","article-title":"Outcomes and predictors of mortality in patients with KPC-Kp infections treated with meropenem vaborbactam: an observational multicenter study","volume":"11","author":"Tumbarello","year":"2024","journal-title":"Open Forum Infect. Dis."},{"key":"B21","unstructured":"The medicines company\n \n \n 2017"},{"key":"B22","unstructured":"EPAR product information\n \n \n 2023"},{"key":"B23","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1007\/s40265-023-01893-6","article-title":"Extended and continuous infusion of novel protected \u03b2-Lactam antibiotics: a narrative review","volume":"83","author":"Venuti","year":"2023","journal-title":"Drugs"},{"key":"B24","doi-asserted-by":"publisher","first-page":"7232","DOI":"10.1128\/AAC.01713-15","article-title":"Meropenem-RPX7009 concentrations in plasma, epithelial lining fluid, and alveolar macrophages of healthy adult subjects","volume":"59","author":"Wenzler","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"B25","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1007\/s40121-018-0214-1","article-title":"Effect and safety of meropenem-vaborbactam versus best-available therapy in patients with carbapenem-resistant enterobacteriaceae infections: the TANGO II randomized clinical trial","volume":"7","author":"Wunderink","year":"2018","journal-title":"Infect. Dis. Ther."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e00115","DOI":"10.1128\/CMR.00115-20","article-title":"New \u03b2-Lactam-\u03b2-Lactamase inhibitor combinations","volume":"34","author":"Yahav","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"B27","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s40265-017-0851-9","article-title":"Imipenem-relebactam and meropenem-Vaborbactam: two novel Carbapenem-\u03b2-Lactamase inhibitor combinations","volume":"78","author":"Zhanel","year":"2018","journal-title":"Drugs"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1887991\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T08:38:23Z","timestamp":1786091903000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1887991\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":27,"alternative-id":["10.3389\/fphar.2026.1887991"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1887991","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]},"article-number":"1887991"}}