{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T20:44:47Z","timestamp":1780951487596,"version":"3.54.1"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,9,10]],"date-time":"2015-09-10T00:00:00Z","timestamp":1441843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>In view of the increasing prevalence of obesity in adolescents, the aim of this study was to determine the pharmacokinetics of the CYP3A substrate midazolam and its metabolites in overweight and obese adolescents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Overweight (BMI for age \u2265 85<jats:sup>th<\/jats:sup> percentile) and obese (BMI for age \u2265 95<jats:sup>th<\/jats:sup> percentile) adolescents undergoing surgery received 2 or 3\u2009mg intravenous midazolam as a sedative drug pre\u2010operatively. Blood samples were collected until 6 or 8\u2009h post\u2010dose. Population pharmacokinetic modelling and systematic covariate analysis were performed using <jats:sc>nonmem<\/jats:sc> 7.2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nineteen overweight and obese patients with a mean body weight of 102.7\u2009kg (62\u2013149.8\u2009kg), a mean BMI of 36.1\u2009kg\u2009m<jats:sup>\u22122<\/jats:sup> (24.8\u201355\u2009kg\u2009m<jats:sup>\u22122<\/jats:sup>), and a mean age of 15.9\u2009years (range 12.5\u201318.9\u2009years) were included. In the model for midazolam and metabolites, total body weight was not of influence on clearance (0.66\u2009l\u2009min<jats:sup>\u22121<\/jats:sup> (RSE 8.3%)), while peripheral volume of distribution of midazolam (154\u2009l (11.2%)), increased substantially with total body weight (<jats:italic>P<\/jats:italic> &lt; 0.001). The increase in peripheral volume could be explained by excess body weight (WT<jats:sub>excess<\/jats:sub>) instead of body weight related to growth (WT<jats:sub>for age and length<\/jats:sub>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The pharmacokinetics of midazolam and its metabolites in overweight and obese adolescents show a marked increase in peripheral volume of distribution and a lack of influence on clearance. The findings may imply a need for a higher initial infusion rate upon initiation of a continuous infusion in obese adolescents.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12693","type":"journal-article","created":{"date-parts":[[2015,6,4]],"date-time":"2015-06-04T20:23:24Z","timestamp":1433449404000},"page":"1185-1196","source":"Crossref","is-referenced-by-count":47,"title":["Population pharmacokinetics of midazolam and its metabolites in overweight and obese adolescents"],"prefix":"10.1111","volume":"80","author":[{"given":"Anne","family":"van Rongen","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy St. Antonius Hospital  Nieuwegein the Netherlands"},{"name":"Division of Pharmacology, Leiden Academic Center for Drug Research Leiden University  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janelle D.","family":"Vaughns","sequence":"additional","affiliation":[{"name":"Division of Anesthesiology and Pain Medicine Children's National Medical Center  Washington DC USA"},{"name":"Division of Clinical Pharmacology Children's National Medical Center  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh S.","family":"Moorthy","sequence":"additional","affiliation":[{"name":"Laboratory for Applied PK\/PD Children's Hospital of Philidelphia  Philidelphia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Barrett","sequence":"additional","affiliation":[{"name":"Laboratory for Applied PK\/PD Children's Hospital of Philidelphia  Philidelphia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherijne A. 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