{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:24:25Z","timestamp":1791242665458,"version":"4.1.0"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"crossref","award":["202240349"],"award-info":[{"award-number":["202240349"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Academic Leaders Training Program of Shanghai Pudong New Area Health Commission","award":["PWRd2024-04"],"award-info":[{"award-number":["PWRd2024-04"]}]},{"name":"Medical Discipline Construction Program of Shanghai Pudong New Area Health Commission","award":["PWZxk2022-26"],"award-info":[{"award-number":["PWZxk2022-26"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,5,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Linezolid, an oxazolidinone antibiotic, is used in patients with liver or kidney disease. However, the effects and mechanisms of hepatic impairment or renal failure on the pharmacokinetics of linezolid and its metabolites (PNU-142586 and PNU-142300) remain unclear. We used carbon tetrachloride-induced impaired hepatic function and 5\/6 nephrectomy-induced renal failure rat models to investigate linezolid and metabolite pharmacokinetics. Isolated primary rat hepatocytes were used to evaluate the impact of hepatic impairment or renal failure on linezolid metabolism. Uptake and efflux transport studies were also conducted. The influence of hepatic impairment or renal failure on the pharmacokinetics of linezolid and two metabolites did not differ between intragastric gavage and intravenous administration in rats. Linezolid did not accumulate in the brain, heart, lung, liver, kidney, and small intestinal tissues of the hepatic impairment or renal failure rats. And PNU-142300 did not accumulate in the liver or kidney tissue. Compared to the isolated normal rat hepatocytes, the\n              <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n              hepatic clearance of linezolid in hepatic impairment and renal failure rat hepatocytes decreased by 61.3% and 44.1%, respectively. Organic anion transporting polypeptide (OATP)1B1, OATP1B3, OATP2B1, Na+-taurocholate co-transporting polypeptide (NTCP), organic anion transporter (OAT)1, OAT3, multidrug resistance-associated protein 2 (MRP2), or multidrug resistance protein 1 (MDR) did not mediate linezolid transport. Hepatic impairment primarily increases linezolid exposure through reduced hepatic metabolism, whereas renal failure increases both linezolid and two metabolites exposure through reduced hepatic metabolism and renal glomerular filtration. These findings guide adjusting the dose of linezolid in patients with hepatic and renal insufficiency.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01892-24","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T13:01:32Z","timestamp":1744635692000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Impact of hepatic impairment and renal failure on the pharmacokinetics of linezolid and its metabolites: contribution of hepatic metabolism and renal excretion"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8517-6541","authenticated-orcid":false,"given":"Jinyao","family":"Liu","sequence":"first","affiliation":[{"name":"Postgraduate Training Base at Shanghai Pudong New Area Gongli Hospital, Ningxia Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Pang","sequence":"additional","affiliation":[{"name":"Postgraduate Training Base at Shanghai Pudong New Area Gongli Hospital, Ningxia Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shanghai Pudong New Area Gongli Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shanghai Pudong New Area Gongli Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shanghai Pudong New Area Gongli Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Shanghai Pudong New Area Gongli Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4344-1845","authenticated-orcid":true,"given":"Jing","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shanghai Pudong New Area Gongli Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1590\/1806-9282.66.s1.3"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.03.017"},{"key":"e_1_3_4_4_2","first-page":"1965","article-title":"Bacterial infections in the context of chronic liver disease","volume":"16","author":"Perdikis KC","year":"2020","unstructured":"Perdikis KC, Goossens N, Carballo S. 2020. 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