{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T10:38:13Z","timestamp":1782902293145,"version":"3.54.5"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"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. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The preclinical phase of innovative drug research and development involves a comprehensive assessment of multiple variables that may influence therapeutic outcomes and safety profiles. Although injection rate represents a potentially modifiable parameter in pharmacological studies, its specific effects on experimental outcomes remain insufficiently characterized in animal models. This study systematically explored the relationship between the intravenous injection rates of three anesthetics and their pharmacodynamic and pharmacokinetic responses in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Three anesthetics were administered to rats via intravenous bolus at varying rates: fast (0.06 mL\/s), medium (0.02 mL\/s), and slow (0.01 mL\/s). Quantitative behavioral assessments were conducted to determine onset latency and duration of anesthesia. Comprehensive safety evaluations included invasive hemodynamic monitoring, respiratory frequency measurements, and myoclonus scoring. Pharmacokinetic profiling was performed using plasma samples analyzed by validated HPLC and HPLC-MS techniques.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Faster injection significantly altered pharmacodynamic profiles, with the fast group showing shorter onset latency and longer duration of effect compared to the slow group. However, this kinetic advantage was associated with a higher incidence of adverse events, including transient hypotension, increased respiratory depression, and more severe myoclonus. Pharmacokinetic analyses revealed dose-rate-dependent plasma concentration profiles, with C\n                      <jats:sub>max<\/jats:sub>\n                      values in the fast group significantly higher than those in the medium and slow groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These findings demonstrate that injection rate directly influences both therapeutic and adverse effects through alterations in pharmacokinetic parameters, particularly C\n                      <jats:sub>max<\/jats:sub>\n                      . Setting a reasonable injection rate in animal experiments will show positive significance and help reduce related safety risks, especially in the application of anesthetics. In addition, strategically optimizing the injection rate during the development of innovative drugs is expected to improve the predictive validity of translational research.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2025.1696260","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T11:44:54Z","timestamp":1765194294000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of bolus injection rate on the pharmacodynamics and pharmacokinetics of propofol, etomidate and sufentanil in rats"],"prefix":"10.3389","volume":"12","author":[{"given":"Sicheng","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deying","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wensheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1016\/j.clinthera.2017.03.016","article-title":"The new drug conditional approval process in China: challenges and opportunities","volume":"39","author":"Yao","year":"2017","journal-title":"Clin Ther"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"297","DOI":"10.14573\/altex.2112203","article-title":"Perspectives on the evaluation and adoption of complex in vitro models in drug development: workshop with the FDA and the pharmaceutical industry (IQ MPS affiliate)","volume":"39","author":"Baran","year":"2022","journal-title":"ALTEX"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s12871-025-02907-4","article-title":"Pharmacokinetics and pharmacodynamics of ciprofol after continuous infusion in elderly patients","volume":"25","author":"Guo","year":"2025","journal-title":"BMC Anesthesiol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"745","DOI":"10.16571\/j.cnki.1008-8199.2021.07.014","article-title":"Anesthetic efficacy of propofol at two injection rates on the patients undergoing artificial abortion","volume":"34","author":"Xiao","year":"2021","journal-title":"J Med Postgra"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"5500","DOI":"10.13241\/j.cnki.pmb.2012.28.037","article-title":"Analysis of the efficacy and safety on fast-infusion propofol in painless gastrofiberscopy","volume":"12","author":"He","year":"2012","journal-title":"Progress Mod Biomed"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1427755","DOI":"10.3389\/fphar.2024.1427755","article-title":"The efficacy and safety of remimazolam besylate, ciprofol, and propofol during hysteroscopy","volume":"15","author":"Shan","year":"2025","journal-title":"Front Pharmacol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1543086","DOI":"10.3389\/fvets.2025.1543086","article-title":"Rapid quantification and PK-PD modeling of rocuronium bromide in beagles using portable mass spectrometer","volume":"12","author":"Li","year":"2025","journal-title":"Front Vet Sci"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1186\/s12871-024-02644-0","article-title":"The effects of remimazolam combined with sufentanil on respiration, circulation and sedation level in patients undergoing colonoscopy","volume":"24","author":"Sun","year":"2024","journal-title":"BMC Anesthesiol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.bja.2024.09.011","article-title":"Etomidate and its derivatives: time to say goodbye?","volume":"134","author":"Nyman","year":"2025","journal-title":"Br J Anaesth"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.23736\/S0375-9393.21.15517-8","article-title":"Safety and efficacy of remimazolam compared with propofol in induction of general anesthesia","volume":"87","author":"Dai","year":"2021","journal-title":"Minerva Anestesiol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"381","DOI":"10.2147\/DDDT.S401969","article-title":"Comparison of remimazolam tosilate and etomidate on hemodynamics in cardiac surgery: a randomised controlled trial","volume":"17","author":"Hu","year":"2023","journal-title":"Drug Des Devel Ther"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.2147\/DDDT.S449705","article-title":"Effect of S-ketamine on postoperative nausea and vomiting in patients undergoing video-assisted thoracic surgery: a randomized controlled trial","volume":"18","author":"Qi","year":"2024","journal-title":"Drug Des Devel Ther"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1111\/anae.14885","article-title":"Differential frontal alpha oscillations and mechanisms underlying loss of conscious-ness: a comparison between slow and fast propofol infusion rates","volume":"75","author":"Sepulveda","year":"2020","journal-title":"Anaesthesia"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1097\/01.anes.0000278902.15505.f8","article-title":"Influence of administration rate on propofol plasma-effect site equilibration","volume":"107","author":"Struys","year":"1964","journal-title":"Anesthesiology"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/BF00537988","article-title":"Evaluation of psychotropic drugs in rats by ED50-estimation with the up and down method according to Dixon-mood","volume":"260","author":"M\u00fcller-Calgan","year":"1968","journal-title":"Naunyn Schmiedebergs Arch Exp Pathol Pharmakol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.tins.2024.02.006","article-title":"Neurobiological basis of emergence from anesthesia","volume":"47","author":"Song","year":"2024","journal-title":"Trends Neurosci"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.brainres.2006.01.036","article-title":"GABA(a)-R alpha1 subunit knock in mutation leads to abnormal EEG and anesthetic-induced seizure-like activity in mice","volume":"1078","author":"Elsen","year":"2006","journal-title":"Brain Res"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/BF02249408","article-title":"Different behavioral effects of halopefidol, clozapine and thioridazine in a concurrent lever pressing and feeding procedure","volume":"125","author":"Salamone","year":"1996","journal-title":"Psychopharmacology"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1213\/ANE.0000000000006292","article-title":"Etomidate-induced myoclonus in Sprague-Dawley rats involves neocortical glutamate accumulation and N-methyl-d-aspartate receptor activity","volume":"137","author":"Feng","year":"2023","journal-title":"Anesth Analg"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.neuropharm.2011.03.025","article-title":"The influence of manipulations to alter ambient GABA concentrations on the hypnotic and immobilizing actions produced by sevoflurane, propofol, and midazolam","volume":"61","author":"Nishikawa","year":"2011","journal-title":"Neuropharmacology"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1111\/j.1365-2044.1986.tb13271.x","article-title":"Sensitivity to propofol in the elderly","volume":"41","author":"Dundee","year":"1986","journal-title":"Anaesthesia"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e080795","DOI":"10.1136\/bmj-2024-080795","article-title":"Effect of high flow nasal cannula oxygenation on incidence of hypoxia during sedated gastrointestinal endoscopy in patients with obesity: multicentre randomised controlled trial","volume":"5","author":"Wang","year":"2020","journal-title":"BMJ"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1213\/01.ane.0000228870.48028.b5","article-title":"Is depth of anesthesia, as assessed by the Bispectral index, related to postoperative cognitive dysfunction and recovery?","volume":"103","author":"Fatag","year":"2006","journal-title":"Anesth Analg"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1111\/j.1460-9592.2007.02273.x","article-title":"Deep propofol sedation for vacuum-assisted bite-block immobilization in children undergoing proton radiation therapy of cranial tumors","volume":"17","author":"Weiss","year":"2007","journal-title":"Pediatr Anesth"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1507616","DOI":"10.3389\/fphar.2024.1507616","article-title":"Comparative efficacy and safety of 20 intravenous pharmaceutical intervention for prevention of etomidate-induced myoclonus: a systematic review and Bayesian network meta-analysis","volume":"15","author":"Chen","year":"2025","journal-title":"Front Pharmacol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/S0007-1935(94)80034-0","article-title":"Models for assessing the relationship between drug concentration and drug effect in performance horses","volume":"150","author":"Kamerling","year":"1994","journal-title":"Br Vet J"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e0181124","DOI":"10.1128\/aac.01811-24","article-title":"Distribution of acyclovir in central nervous system compartments: a porcine pharmacokinetic model","volume":"69","author":"Mariager","year":"2025","journal-title":"Antimicrob Agents Chemother"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1007\/s00280-010-1522-7","article-title":"Safety and pharmacokinetics of intrathecal administration of pemetrexed in rats","volume":"68","author":"Sun","year":"2011","journal-title":"Cancer Chemother Pharmacol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.bja.2020.09.022","article-title":"Explaining anaesthetic hysteresis with effect-site equilibration","volume":"126","author":"Proekt","year":"2021","journal-title":"Br J Anaesth"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1111\/bcp.12286","article-title":"Pharmacokinetic-pharmacodynamic modelling in anaesthesia","volume":"79","author":"Gamb\u00fas","year":"2015","journal-title":"Br J Clin Pharmacol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1186\/s40064-016-2011-1","article-title":"The administration of high-dose propofol sedation with manual and target-controlled infusion in children undergoing radiation therapy: a 7-year clinical investigation","volume":"5","author":"Oh","year":"2016","journal-title":"Springer Plus"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1111\/j.1399-6576.2009.02183.x","article-title":"Predictive ability of propofol effect-site concentrations during fast and slow infusion rates","volume":"54","author":"Sepulveda","year":"2010","journal-title":"Acta Anaesth Scand"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e17","DOI":"10.1371\/journal.pctr.0010017","article-title":"The influence of injection rate on the hypnotic effect of propofol during anesthesia: a randomized trial","volume":"1","author":"Blum","year":"2006","journal-title":"PLoS Clin Trials"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2673","DOI":"10.3390\/app14072673","article-title":"The forces associated with bolus injection and continuous infusion techniques during ultrasound targeted nerve contact: an ex vivo study","volume":"14","author":"Agweder","year":"2024","journal-title":"Appl Sci"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1016\/j.bja.2024.02.032","article-title":"Choice of needle and injection rate for fascial plane injection: a randomised controlled study in the soft-embalmed Thiel cadaver","volume":"132","author":"Agweder","year":"2024","journal-title":"Br J Anaesth"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"104136","DOI":"10.1016\/j.esmoop.2025.104136","article-title":"Phase I trial of the combination of the pan-ErbB inhibitor neratinib and mTOR inhibitor everolimus in advanced cancer patients with ErbB family gene alterations","volume":"10","author":"Piha-Paul","year":"2025","journal-title":"ESMO Open"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1002\/psp4.13285","article-title":"A minimal physiologically-based pharmacokinetic modeling platform to predict intratumor exposure and receptor occupancy of an anti-LAG-3 monoclonal antibody","volume":"14","author":"Michelet","year":"2025","journal-title":"CPT Pharmacometrics Syst Pharmacol"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2025.1696260\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T11:44:56Z","timestamp":1765194296000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2025.1696260\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,8]]},"references-count":37,"alternative-id":["10.3389\/fvets.2025.1696260"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2025.1696260","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,8]]},"article-number":"1696260"}}