{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T21:25:16Z","timestamp":1766697916217,"version":"3.37.3"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,1,21]],"date-time":"2015-01-21T00:00:00Z","timestamp":1421798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1RR025744"],"award-info":[{"award-number":["UL1RR025744"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Etomidate is a rapid\u2010onset, short\u2010acting hypnotic medication administered for the induction of anesthesia. It is currently approved by the Food and Drug Administration for use in older children and adults. Pharmacokinetic data to help guide dosing in neonates and infants are lacking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim of this study was to determine the pharmacokinetics of etomidate in neonates and infants with congenital heart disease undergoing cardiac surgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four neonates and 16 infants, postnatal age 0.3\u201311.7\u2009months, requiring open\u2010heart surgery received 0.3\u2009mg\/kg of etomidate administered as a single intravenous dose prior to surgery. Blood sampling for plasma etomidate concentration occurred immediately following etomidate administration until the initiation of cardiopulmonary bypass. A population pharmacokinetic approach using nonlinear mixed\u2010effects modeling was applied to characterize etomidate pharmacokinetics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The pharmacokinetics of etomidate was described by a two\u2010compartment model with first\u2010order elimination. An allometric weight\u2010based model was applied to scale results to a 70\u2009kg adult. Covariates including age and cardiac physiology were not found significantly to impact etomidate pharmacokinetics. The study population was found to have a central and intercompartmental clearance of 0.624\u2009l\/min\/70\u2009kg and 0.44\u2009l\/min\/70\u2009kg, respectively; central and peripheral distribution volume of 9.47\u2009l\/70\u2009kgand 22.8\u2009l\/70\u2009kg, respectively. Inter\u2010individual variability was 94\u2013142% for all parameters and the residual variability was 29%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The clearance of etomidate is lower in neonates and infants with congenital heart disease compared with published values for older children without congenital heart disease. In addition, etomidate pharmacokinetics is highly variable in this pediatric cardiac population. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdd.1924","type":"journal-article","created":{"date-parts":[[2014,11,5]],"date-time":"2014-11-05T21:05:09Z","timestamp":1415221509000},"page":"104-114","source":"Crossref","is-referenced-by-count":13,"title":["Population pharmacokinetics of etomidate in neonates and infants with congenital heart disease"],"prefix":"10.1002","volume":"36","author":[{"given":"Felice","family":"Su","sequence":"first","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Stanford USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed H.","family":"El\u2010Komy","sequence":"additional","affiliation":[{"name":"Department of Anesthesia Stanford University School of Medicine  Stanford USA"},{"name":"Department of Pharmaceutics and Industrial Pharmacy Beni\u2010Suef University  Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory B.","family":"Hammer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Stanford USA"},{"name":"Department of Anesthesia Stanford University School of Medicine  Stanford USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Frymoyer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Stanford USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol A.","family":"Cohane","sequence":"additional","affiliation":[{"name":"Department of Anesthesia Stanford University School of Medicine  Stanford USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Drover","sequence":"additional","affiliation":[{"name":"Department of Anesthesia Stanford University School of Medicine  Stanford USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,1,21]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Amidate [package insert]. 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