{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:13:58Z","timestamp":1788527638220,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009399","name":"Peking University Third Hospital","doi-asserted-by":"publisher","award":["BYSYZD2022007"],"award-info":[{"award-number":["BYSYZD2022007"]}],"id":[{"id":"10.13039\/501100009399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009399","name":"Peking University Third Hospital","doi-asserted-by":"publisher","award":["BYSYZD2024022"],"award-info":[{"award-number":["BYSYZD2024022"]}],"id":[{"id":"10.13039\/501100009399","id-type":"DOI","asserted-by":"publisher"}]},{"award":["BYSYZD2022007"],"award-info":[{"award-number":["BYSYZD2022007"]}],"id":[{"id":"https:\/\/ror.org\/04wwqze12","id-type":"ROR","asserted-by":"publisher"}]},{"award":["BYSYZD2024022"],"award-info":[{"award-number":["BYSYZD2024022"]}],"id":[{"id":"https:\/\/ror.org\/04wwqze12","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204522"],"award-info":[{"award-number":["82204522"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82204522"],"award-info":[{"award-number":["82204522"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Meropenem pharmacokinetic variability in sepsis often leads to suboptimal exposure and therapeutic failure. Existing covariates like creatinine clearance (CLcr) only partially explain this variability. This study evaluated pyridoxic acid (PDA), an endogenous biomarker of OAT1\/3 transporters, as a novel covariate to quantify active tubular secretion and explore pharmacokinetic\/pharmacodynamic (PK\/PD) linkages with clinical outcomes. Methods: A population PK (PopPK) model was constructed using data from a prospective septic cohort (n = 28). Subsequent exposure-response analysis was conducted in an expanded cohort (n = 49), and Monte Carlo simulations were utilized to evaluate various dosing regimens. Results: The PopPK analysis suggested that PDA may complement CLcr in characterizing meropenem clearance variability. While CLcr explained 10.7% of inter-individual variability (IIV) in clearance, the inclusion of PDA explained an additional 13.7%, reducing total IIV from 50.8% to 26.4%. Achieving a stringent target of 100%fT &gt; 4MIC was significantly associated with a rapid decline in procalcitonin (p = 0.027), establishing a key PD endpoint. Simulations demonstrated that standard dosing (1 g q8h, 1 h infusion) is insufficient for patients with normal or augmented renal function. Target attainment was highly dependent on PDA levels. Conclusions: PDA is a valuable translational biomarker for OAT-mediated clearance. To achieve 100%fT &gt; 4MIC, we recommend (i) 1 g q8h with 3 h infusion for patients with low CLcr and high PDA levels (MIC = 0.5 mg\/L), and (ii) an intensified regimen of 2 g q8h with 3 h infusion for patients with normal CLcr and low PDA levels or high resistance risk (MIC \u2265 2 mg\/L).<\/jats:p>","DOI":"10.3390\/pharmaceutics18091113","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T12:20:19Z","timestamp":1788524419000},"page":"1113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pyridoxic Acid as a Novel Endogenous Biomarker for OAT-Mediated Clearance of Meropenem: A Population Pharmacokinetic Modeling and PK\/PD-Response Analysis in Patients with Sepsis"],"prefix":"10.3390","volume":"18","author":[{"given":"Zihan","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China"},{"name":"Drug Clinical Trial Center, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4382-3704","authenticated-orcid":false,"given":"Hao","family":"Liang","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Qin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"project-administration","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Weijie","family":"Kong","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center, Peking University Third Hospital, Beijing 100191, China"},{"name":"Department of Clinical Pharmacology, Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai 200135, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"project-administration","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Yipeng","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Xueting","family":"Yao","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"given":"Feifei","family":"Feng","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Yuyan","family":"Jin","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Wenting","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Haiyan","family":"Li","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center, Peking University Third Hospital, Beijing 100191, China"},{"name":"Center of Clinical Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Ming","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China"},{"name":"Center of Infectious Disease, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0608-8192","authenticated-orcid":false,"given":"Dongyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center, Peking University Third Hospital, Beijing 100191, China"},{"name":"Center of Clinical Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Ning","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China"},{"name":"Center of Infectious Disease, Peking University Third Hospital, Beijing 100191, 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