{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:39:08Z","timestamp":1792510748372,"version":"4.5.0"},"reference-count":18,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Evopoint Biosciences USA, Inc.","award":["Funobactam Renal Impairment Study"],"award-info":[{"award-number":["Funobactam Renal Impairment Study"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>A phase 1, open-label study was conducted to investigate the effect of renal impairment (RI) on pharmacokinetics (PK) and safety of funobactam plus imipenem\/cilastatin. Participants were enrolled and assigned to one of five cohorts based on renal function category: normal renal function, mild RI, moderate RI, severe RI, and end-stage renal disease (ESRD) requiring hemodialysis (HD). Participants received a single-dose of funobactam with imipenem and cilastatin by intravenous infusion administered over 60 min. Serial blood and urine samples were collected for non-compartmental PK analysis. Compared to participants with normal renal function, the geometric mean ratio (90% confidence interval) of plasma area under the curve (AUC0-\u221e) for funobactam, imipenem, and cilastatin increased with RI from mild (1.32 [1.04, 1.66], 1.37 [1.04, 1.79], and 1.27 [0.90, 1.78], respectively) to ESRD requiring HD (9.58 [7.59, 12.10], 2.69 [2.06, 3.52], and 15.15 [10.8, 21.3], respectively). The renal clearance for funobactam, imipenem, and cilastatin decreased progressively from normal renal function (3.93 \u00b1 1.12 L\/h, 4.95 \u00b1 2.40 L\/h, and 6.98 \u00b1 2.75 L\/h, respectively) to severe RI (0.94 \u00b1 0.37 L\/h, 1.16 \u00b1 0.34 L\/h, and 1.70 \u00b1 0.60 L\/h, respectively). Plasma clearance of funobactam, imipenem, and cilastatin correlated (r \u22650.93) with creatinine clearance and the estimated glomerular filtration rate. The treatment was well tolerated, with no deaths, severe adverse events, or discontinuation due to adverse events. Dosage adjustments of funobactam, imipenem, and cilastatin will be needed in patients with renal impairment or ESRD requiring HD.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>CLINICAL TRIALS<\/jats:title>\n                      <jats:p>\n                        This study is registered with ClinicalTrials.gov as\n                        <jats:related-object xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" document-id=\"NCT04787562\" document-id-type=\"clinical-trial-number\" source-id=\"ClinicalTrials.gov\" source-id-type=\"registry-name\" source-type=\"clinical-trials-registry\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04787562\">NCT04787562<\/jats:related-object>\n                        .\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00808-26","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:00:16Z","timestamp":1787835616000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Impact of renal impairment on pharmacokinetics, safety, and tolerability of funobactam, combined with imipenem and cilastatin"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7200-7346","authenticated-orcid":true,"given":"Keith A.","family":"Rodvold","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02mpq6x41","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Illinois Chicago","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grigor","family":"Mamikonyan","sequence":"additional","affiliation":[{"name":"Clinartis LLC","place":["Hollywood, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Evopoint Biosciences Co Ltd","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"McRoberts","sequence":"additional","affiliation":[{"name":"Pharmaron Germantown","place":["Germantown, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dyal","family":"Garg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01c127k53","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Research Services Inc.","place":["Boynton Beach, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Preston","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02dgjyy92","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Clinical Pharmacology, University of Miami","place":["Miami, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Marabury","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/000x1tr98","id-type":"ROR","asserted-by":"publisher"}],"name":"Orlando Clinical Research Center","place":["Orlando, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijie","family":"Le","sequence":"additional","affiliation":[{"name":"Evopoint Biosciences Co Ltd","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7587-5476","authenticated-orcid":true,"given":"Jianguo","family":"Li","sequence":"additional","affiliation":[{"name":"Evopoint Biosceinces USA, Inc.","place":["Concord, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2022.07.006"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkad242"},{"key":"e_1_3_5_4_2","first-page":"1729,","volume-title":"Abstr. P-1520. ESCMID Global 2024, 34th Congress of the European Society of Clinical Microbiology and Infectious Diseases","author":"Li J","year":"2024","unstructured":"Li J, Shi Q, Zhao H, Hackel M, Bradford PA, Le M. 2024. In vitro activity of funobactam (XNW4107) combined with imipenem against Gram-negative isolates collected in 2021. Abstr. P-1520. ESCMID Global 2024, 34th Congress of the European Society of Clinical Microbiology and Infectious Diseases. , p 1729,CMI Communications, Barcelona, Spain. https:\/\/www.sciencedirect.com\/science\/article\/pii\/S2950590924000131."},{"key":"e_1_3_5_5_2","first-page":"2775,","volume-title":"Abstr. P-2510. ESCMID Global 2024, 34th Congress of the European Society of Clinical Microbiology and Infectious Diseases","author":"Li J","year":"2024","unstructured":"Li J, Shi Q, Zhao H, Mcroberts A, Sanghvi M, Depertrillo P, Le M. 2024. Pharmacokinetics, safety, and tolerability of funobactam alone or in combination with imipenem\/cilastatin in healthy subjects. Abstr. P-2510. ESCMID Global 2024, 34th Congress of the European Society of Clinical Microbiology and Infectious Diseases. , p 2775,CMI Communications, Barcelona, Spain. https:\/\/www.sciencedirect.com\/science\/article\/pii\/S2950590924000131."},{"key":"e_1_3_5_6_2","unstructured":"Anonymous. 2018. Primaxin (imipenem and cilastatin) for injection prescribing information. Merck & Co. Inc Whitehouse Station NJ. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/050587s081lbl.pdf."},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200039030-00002"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.26.5.715"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00524-26"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-130-6-199903160-00002"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00280-18"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14204"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/18.supplement_e.115"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(85)90102-0"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.190"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.182"},{"key":"e_1_3_5_18_2","unstructured":"Center for Drug Evaluation and Research. 2020. Pharmacokinetics in patients with impaired renal function\u2014study design data analysis and impact on dosing and labeling. Available from: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/pharmacokinetics-patients-impaired-renal-function-study-design-data-analysis-and-impact-dosing-and"},{"key":"e_1_3_5_19_2","unstructured":"Anonymous. 2019. Recabrio (imipenem cilastatin relebactam) for injection for intravenous use prescribing information. Merck & Co. Inc Whitehouse Station NJ. https:\/\/www. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/212819s000lbl.pdf."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00808-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00808-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:49:29Z","timestamp":1792507769000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00808-26"}},"subtitle":[],"editor":[{"given":"Vincent H.","family":"Tam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":18,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10,7]]}},"alternative-id":["10.1128\/aac.00808-26"],"URL":"https:\/\/doi.org\/10.1128\/aac.00808-26","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"assertion":[{"value":"2026-06-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00808-26"}}