{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:08:30Z","timestamp":1793210910466,"version":"4.5.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007452","name":"Wu Jieping Medical Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007452","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Objectives:<\/jats:bold> Teicoplanin has been extensively used in the treatment for infections caused by gram-positive bacteria including methicillin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA). However, current teicoplanin treatment is challenging due to relatively low and variable concentrations under standard dosage regimens. This study aimed to investigate the population pharmacokinetics (PPK) characteristics of teicoplanin in adult sepsis patients and provide recommendations for optimal teicoplanin dosing regimens.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> A total of 249 serum concentration samples from 59 septic patients were prospectively collected in the intensive care unit (ICU). Teicoplanin concentrations were detected, and patients\u2019 clinical data were recorded. PPK analysis was performed using a non-linear, mixed-effect modeling approach. Monte Carlo simulations were performed to evaluate currently recommended dosing and other dosage regimens. The optimal dosing regimens were defined and compared by different pharmacokinetic\/pharmacodynamic parameters, including trough concentration (C<jats:sub>min<\/jats:sub>), the ratio of 24-h area under the concentration-time curve to the minimum inhibitory concentration (AUC<jats:sub>0-24<\/jats:sub>\/MIC), as well as the probability of target attainment (PTA) and the cumulative fraction of response (CFR) against MRSA.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> A two-compartment model adequately described the data. The final model parameter estimates for clearance, central compartment volume of distribution, intercompartmental clearance and peripheral compartment volume were 1.03\u00a0L\/h, 20.1 L, 3.12\u00a0L\/h and 101\u00a0L, respectively. Glomerular filtration rate (GFR) was the only covariate that significantly affected teicoplanin clearance. Model-based simulations revealed that 3 or 5 loading doses of 12\/15\u00a0mg\/kg every 12\u00a0h followed by a maintenance dose of 12\/15\u00a0mg\/kg every 24\u00a0h\u201372\u00a0h for patients with different renal functions were required to achieve a target C<jats:sub>min<\/jats:sub> of 15\u00a0mg\/L and a target AUC<jats:sub>0-24<\/jats:sub>\/MIC of 610. For MRSA infections, PTAs and CFRs were not satisfactory for simulated regimens. Prolonging the dosing interval may be easier to achieve the target AUC<jats:sub>0-24<\/jats:sub>\/MIC than reducing the unit dose for renal insufficient patients.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> A PPK model for teicoplanin in adult septic patients was successfully developed. Model-based simulations revealed that current standard doses may result in undertherapeutic C<jats:sub>min<\/jats:sub> and AUC, and a single dose of at least 12\u00a0mg\/kg may be needed. AUC<jats:sub>0-24<\/jats:sub>\/MIC should be preferred as the PK\/PD indicator of teicoplanin, if AUC estimation is unavailable, in addition to routine detection of teicoplanin C<jats:sub>min<\/jats:sub> on Day 4, follow-up therapeutic drug monitoring at steady-state is recommended.<\/jats:p>","DOI":"10.3389\/fphar.2023.1132367","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T05:56:38Z","timestamp":1682661398000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Population pharmacokinetic analysis and dosing regimen optimization of teicoplanin in critically ill patients with sepsis"],"prefix":"10.3389","volume":"14","author":[{"given":"Chao\u2010Yang","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Li","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si\u2010Miao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruo\u2010Ming","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang\u2010Lin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang\u2010Ling","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Min","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,28]]},"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<sub\/>","volume":"46","author":"Abdul-Aziz","year":"2020","journal-title":"Intensive Care Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1186\/s13054-018-2186-7","article-title":"Characteristics, management, and in-hospital mortality among patients with severe sepsis in intensive care units in Japan: The FORECAST study","volume":"22","author":"Abe","year":"2018","journal-title":"Crit. Care"},{"key":"B3","doi-asserted-by":"publisher","first-page":"616","DOI":"10.3349\/ymj.2011.52.4.616","article-title":"Teicoplanin dosing strategy for treatment of Staphylococcus aureus in Korean patients with neutropenic fever","volume":"52","author":"Ahn","year":"2011","journal-title":"Yonsei Med. J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1007\/s40262-020-00945-4","article-title":"Population pharmacokinetics of unbound and total teicoplanin in critically ill pediatric patients","volume":"60","author":"Aulin","year":"2021","journal-title":"Clin. Pharmacokinet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1208\/s12248-011-9255-z","article-title":"Prediction-corrected visual predictive checks for diagnosing nonlinear mixed-effects models","volume":"13","author":"Bergstrand","year":"2011","journal-title":"AAPS J."},{"key":"B6","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1097\/01.inf.0000094940.81959.14","article-title":"Predicting efficacy of antiinfectives with pharmacodynamics and Monte Carlo simulation","volume":"22","author":"Bradley","year":"2003","journal-title":"Pediatr. Infect. Dis. J."},{"key":"B7","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/j.ijantimicag.2008.05.012","article-title":"Recommendations to achieve rapid therapeutic teicoplanin plasma concentrations in adult hospitalised patients treated for sepsis","volume":"32","author":"Brink","year":"2008","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B57","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.ijantimicag.2015.01.015","article-title":"Albumin concentration significantly impacts on free teicoplanin plasma concentrations in non-critically ill patients with chronic bone sepsis","volume":"45","author":"Brink","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B8","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1093\/jac\/dkx473","article-title":"Population pharmacokinetics of total and unbound teicoplanin concentrations and dosing simulations in patients with haematological malignancy","volume":"73","author":"Byrne","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"B9","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1016\/j.cmi.2017.02.032","article-title":"Population pharmacokinetics of teicoplanin and attainment of pharmacokinetic\/pharmacodynamic targets in adult patients with haematological malignancy","volume":"23","author":"Byrne","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"B10","doi-asserted-by":"publisher","first-page":"Cd007022","DOI":"10.1002\/14651858.CD007022.pub2","article-title":"Teicoplanin versus vancomycin for proven or suspected infection","volume":"6","author":"Cavalcanti","year":"2010","journal-title":"Cochrane Database Syst. Rev."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2804","DOI":"10.1093\/jac\/dkx242","article-title":"Population pharmacokinetics of teicoplanin administered by subcutaneous or intravenous route and simulation of optimal loading dose regimen","volume":"72","author":"Cazaubon","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"B12","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1128\/cmr.00081-09","article-title":"Community-associated methicillin-resistant Staphylococcus aureus: Epidemiology and clinical consequences of an emerging epidemic","volume":"23","author":"David","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1389.e1","DOI":"10.1016\/j.cmi.2022.05.007","article-title":"Cefepime population pharmacokinetics and dosing regimen optimization in critically ill children with different renal function","volume":"28","author":"de Cacqueray","year":"2022","journal-title":"Clin. Microbiol. Infect."},{"key":"B14","doi-asserted-by":"publisher","first-page":"14","DOI":"10.5414\/cp201374","article-title":"An assessment of teicoplanin use and monitoring serum levels in a Chinese teaching hospital","volume":"49","author":"Dong","year":"2011","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"B15","volume-title":"Summary of product characteristics","year":"2022"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1128\/aac.31.8.1255","article-title":"Pharmacokinetics of teicoplanin in renal failure","volume":"31","author":"Falcoz","year":"1987","journal-title":"Antimicrob. Agents Chemother."},{"key":"B17","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1080\/17425255.2020.1750597","article-title":"Pharmacokinetic and pharmacodynamic considerations in antimicrobial therapy for sepsis","volume":"16","author":"Fujii","year":"2020","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"552","DOI":"10.3389\/fphar.2020.00552","article-title":"Population pharmacokinetics and dosage optimization of teicoplanin in children with different renal functions","volume":"11","author":"Gao","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1093\/jac\/dkl017","article-title":"Guidelines for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the UK","volume":"57","author":"Gemmell","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"B20","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1016\/j.idc.2009.06.009","article-title":"Use of antibacterial agents in renal failure","volume":"23","author":"Gilbert","year":"2009","journal-title":"Infect. Dis. Clin. North Am."},{"key":"B21","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1093\/jac\/dkab499","article-title":"Clinical practice guidelines for therapeutic drug monitoring of teicoplanin: A consensus review by the Japanese society of Chemotherapy and the Japanese society of therapeutic drug monitoring","volume":"77","author":"Hanai","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"key":"B22","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1093\/jac\/45.6.835","article-title":"Teicoplanin therapy for Staphylococcus aureus septicaemia: Relationship between pre-dose serum concentrations and outcome","volume":"45","author":"Harding","year":"2000","journal-title":"J. Antimicrob. Chemother."},{"key":"B56","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1248\/bpb.30.952","article-title":"Comparison of pharmacokinetics of individual teicoplanin components in patients","volume":"30","author":"Hanada","year":"2007","journal-title":"Biol. Pharm. Bull."},{"key":"B23","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.jiac.2016.01.019","article-title":"Retrospective study of teicoplanin loading regimen that rapidly achieves target 15-30 \u03bcg\/mL serum trough concentration","volume":"22","author":"Kato","year":"2016","journal-title":"J. Infect. Chemother."},{"key":"B24","first-page":"119","article-title":"Therapeutic drug monitoring survey of anti-MRSA agents in Japan","volume":"58","author":"Kobayashi","year":"2010","journal-title":"Jpn. J. Chemother."},{"key":"B25","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1186\/cc12698","article-title":"Antibiotics for the critically ill: More than just selecting appropriate initial therapy","volume":"17","author":"Kollef","year":"2013","journal-title":"Crit. Care"},{"key":"B26","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1186\/cc1022","article-title":"Optimizing antibiotic therapy in the intensive care unit setting","volume":"5","author":"Kollef","year":"2001","journal-title":"Crit. Care"},{"key":"B27","doi-asserted-by":"publisher","first-page":"019711-19","DOI":"10.1128\/aac.01971-19","article-title":"Population pharmacokinetics of teicoplanin in preterm and term neonates: Is it time for a new dosing regimen?","volume":"64","author":"Kontou","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"B28","doi-asserted-by":"publisher","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"3315","DOI":"10.1128\/aac.00113-08","article-title":"Relationship between vancomycin MIC and failure among patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin","volume":"52","author":"Lodise","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1128\/aac.40.5.1242","article-title":"Population pharmacokinetic study of teicoplanin in severely neutropenic patients","volume":"40","author":"Lortholary","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"B31","doi-asserted-by":"publisher","first-page":"15","DOI":"10.2147\/cpaa.S96143","article-title":"Pharmacokinetic\/pharmacodynamic analysis of teicoplanin in patients with MRSA infections","volume":"8","author":"Matsumoto","year":"2016","journal-title":"Clin. Pharmacol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1007\/s11096-016-0308-3","article-title":"Change of teicoplanin loading dose requirement for incremental increases of systemic inflammatory response syndrome score in the setting of sepsis","volume":"38","author":"Nakano","year":"2016","journal-title":"Int. J. Clin. Pharm."},{"key":"B33","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1097\/01.Ccm.0000050464.70382.D6","article-title":"Appropriate use of antimicrobial agents: Challenges and strategies for improvement","volume":"31","author":"Niederman","year":"2003","journal-title":"Crit. Care Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1002\/cpdd.684","article-title":"Population pharmacokinetics and pharmacodynamics of teicoplanin and C-reactive protein in hospitalized patients with gram-positive infections","volume":"9","author":"Ogami","year":"2020","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1097\/ccm.0000000000003342","article-title":"Epidemiology and costs of sepsis in the United States-an analysis based on timing of diagnosis and severity level","volume":"46","author":"Paoli","year":"2018","journal-title":"Crit. Care Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1093\/jac\/dkg147","article-title":"Teicoplanin therapeutic drug monitoring in critically ill patients: A retrospective study emphasizing the importance of a loading dose","volume":"51","author":"Pea","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"B37","doi-asserted-by":"publisher","first-page":"3382","DOI":"10.1093\/jac\/dkx289","article-title":"Pharmacodynamics of teicoplanin against MRSA","volume":"72","author":"Ramos-Mart\u00edn","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"B38","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1056\/NEJMp1707170","article-title":"Recognizing sepsis as a global health priority - a WHO resolution","volume":"377","author":"Reinhart","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1093\/jac\/dku564","article-title":"Plasma and target-site subcutaneous tissue population pharmacokinetics and dosing simulations of cefazolin in post-trauma critically ill patients","volume":"70","author":"Roberts","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1093\/jac\/dkn037","article-title":"Teicoplanin pharmacodynamics in reference to the accessory gene regulator (agr) in Staphylococcus aureus using an in vitro pharmacodynamic model","volume":"61","author":"Rose","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"B41","doi-asserted-by":"publisher","first-page":"184","DOI":"10.2165\/00003088-199018030-00002","article-title":"Clinical pharmacokinetics of teicoplanin","volume":"18","author":"Rowland","year":"1990","journal-title":"Clin. Pharmacokinet."},{"key":"B42","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/s0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990-2017: Analysis for the global burden of disease study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"B43","doi-asserted-by":"publisher","first-page":"S35","DOI":"10.1086\/491712","article-title":"The pharmacokinetic and pharmacodynamic properties of vancomycin","volume":"42","author":"Rybak","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"B44","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1097\/ftd.0000000000000906","article-title":"Population pharmacokinetics of teicoplanin and its dosing recommendations for neutropenic patients with augmented renal clearance for hematological malignancies","volume":"43","author":"Sako","year":"2021","journal-title":"Ther. Drug Monit."},{"key":"B45","doi-asserted-by":"publisher","first-page":"ofy313","DOI":"10.1093\/ofid\/ofy313","article-title":"Sepsis in intensive care unit patients: Worldwide data from the intensive care over nations audit","volume":"5","author":"Sakr","year":"2018","journal-title":"Open Forum Infect. Dis."},{"key":"B46","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1093\/bja\/aex234","article-title":"Epidemiology of sepsis and septic shock in critical care units: Comparison between sepsis-2 and sepsis-3 populations using a national critical care database","volume":"119","author":"Shankar-Hari","year":"2017","journal-title":"Br. J. Anaesth."},{"key":"B47","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"Jama"},{"key":"B48","doi-asserted-by":"publisher","first-page":"2155","DOI":"10.1093\/jac\/dkq266","article-title":"Analyses of teicoplanin concentrations from 1994 to 2006 from a UK assay service","volume":"65","author":"Tobin","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"B49","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.jiac.2013.08.006","article-title":"High-dose regimen to achieve novel target trough concentration in teicoplanin","volume":"20","author":"Ueda","year":"2014","journal-title":"J. Infect. Chemother."},{"key":"B50","doi-asserted-by":"publisher","first-page":"356","DOI":"10.5414\/cp202247","article-title":"Factors on trough teicoplanin levels, associations between levels, efficacy and safety in patients with gram-positive infections","volume":"53","author":"Wang","year":"2015","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"B51","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1080\/1120009x.2021.1931758","article-title":"Optimization of dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin against methicillin-resistant Staphylococcus aureus in neutropenic patients with cancer by Monte Carlo simulations","volume":"33","author":"Wei","year":"2021","journal-title":"J. Chemother."},{"key":"B52","doi-asserted-by":"publisher","first-page":"e01015-17","DOI":"10.1128\/aac.01015-17","article-title":"Population pharmacokinetics and dose optimization of teicoplanin during venoarterial extracorporeal membrane oxygenation","volume":"61","author":"Wi","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0924-8579(94)90049-3","article-title":"A critical review of the dosage of teicoplanin in Europe and the USA","volume":"4","author":"Wilson","year":"1994","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B54","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1128\/aac.00520-13","article-title":"Multicenter prospective observational study of the comparative efficacy and safety of vancomycin versus teicoplanin in patients with health care-associated methicillin-resistant Staphylococcus aureus bacteremia","volume":"58","author":"Yoon","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"B55","doi-asserted-by":"publisher","first-page":"594562","DOI":"10.3389\/fphar.2020.594562","article-title":"Population pharmacokinetics and model-based dosing optimization of teicoplanin in pediatric patients","volume":"11","author":"Zhang","year":"2020","journal-title":"Front. Pharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1132367\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T05:56:43Z","timestamp":1682661403000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1132367\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,28]]},"references-count":57,"alternative-id":["10.3389\/fphar.2023.1132367"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1132367","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,28]]},"article-number":"1132367"}}