{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T13:15:55Z","timestamp":1773321355310,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T00:00:00Z","timestamp":1545177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Manchester University Foundation Trust"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Anesthesia"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The local anesthetic, levobupivacaine, is the safer enantiomer of racemic bupivacaine. Present protocols for levobupivacaine are based on studies and pharmacokinetic modeling with racemic bupivacaine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>The aim is to investigate total serum levobupivacaine concentrations after a caudalepidural loading dose followed by a maintenance infusion over 48 hours in infants aged 3\u20106 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The clinical trial was conducted in eight infants aged 3\u20106\u00a0months, undergoing bladder exstrophy repair. Pharmacokinetic modeling allowed optimization of clinical sampling to measure total levobupivacaine and \u03b1<jats:sub>1<\/jats:sub>\u2010acid glycoprotein and prediction of the effect of \u03b1<jats:sub>1<\/jats:sub>\u2010acid glycoprotein on levobupivacaine plasma protein binding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The observed median total levobupivacaine serum concentration was 0.30\u00a0mg\/L (range: 0.20\u20100.70\u00a0mg\/L) at 1 hour after the loading dose of 2\u00a0mg\/kg. The median total levobupivacaine concentration after 47\u00a0hours of infusion, at 0.2 mg\/kg\/h, was 1.21\u00a0mg\/L (0.07\u20101.85\u00a0mg\/L). Concentrations of \u03b1<jats:sub>1<\/jats:sub>\u2010acid glycoprotein were found to rise throughout the study period. Pharmacokinetic modeling suggested that unbound levobupivacaine quickly reached steady state at a concentration of approximately 0.03\u00a0mg\/L.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The study allows the development of a pharmacokinetic model, combining levobupivacaine and \u03b1<jats:sub>1<\/jats:sub>\u2010acid glycoprotein data. Modeling indicates that unbound levobupivacaine quickly reaches steady state once the infusion is started. Simulations suggest that it may be possible to continue the infusion beyond 48\u00a0hours.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pan.13548","type":"journal-article","created":{"date-parts":[[2018,11,17]],"date-time":"2018-11-17T20:08:46Z","timestamp":1542485326000},"page":"161-168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A study of the dosage and duration for levobupivacaine infusion by the caudal\u2010epidural route in infants aged 3\u20106 months"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4420-0456","authenticated-orcid":false,"given":"Rita","family":"Vashisht","sequence":"first","affiliation":[{"name":"Department of Paediatric Anaesthesia, Manchester University NHS Foundation Trust Royal Manchester Children\u2019s Hospital Manchester 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