{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T21:39:18Z","timestamp":1769636358207,"version":"3.49.0"},"reference-count":68,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,2,15]],"date-time":"2011-02-15T00:00:00Z","timestamp":1297728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Anesthesia"],"published-print":{"date-parts":[[2011,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Background:\u2002<\/jats:bold> Physiological\u2010based pharmacokinetic models have been used to describe midazolam clearance (CL) maturation. There are no maturation descriptors of CL from neonate to adulthood based on reported estimates at different ages.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Published CL estimates after intravenous administration from time\u2013concentration profiles were used to construct a maturation model based on size and age. Curve fitting was performed using nonlinear mixed effects models.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> There were 16 publications reporting an estimate of CL after intravenous administration in children, although few estimates were available from 44\u201380\u2003weeks postmenstrual age (PMA). CL maturation, standardized to a 70\u2003\u2010kg person was described using the Hill equation. Mature CL was 523 (CV 32%, 95%CI 469, 597)\u2003ml\u00b7min<jats:sup>\u22121<\/jats:sup>\u00b770\u2003kg<jats:sup>\u22121<\/jats:sup>. The maturation half\u2010time was 73.6 (95%CI 59.4, 80.0) weeks PMA and the Hill coefficient 3 (95%CI 2.2, 4.1). Predicted CL changes with age based on this model were in close agreement with physiologically based pharmacokinetic (PBPK) models. A comparison with a published PBPK model predictions revealed a root mean squared prediction error (precision) of 4.0% (95%CI 1.1, 5.8) and bias was \u22120.9% (95%CI \u22124.3, 2.6).<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> Previously published pharmacokinetic parameters can be used to develop maturation models that address gaps in current knowledge regarding the influence of age on a drug\u2019s disposition. If a midazolam sedation target concentration of 0.1\u2003mg\u00b7l<jats:sup>\u22121<\/jats:sup>, similar to that given to adults, is assumed, then we might anticipate steady\u2010state infusion rates of 0.014\u2003mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup> in neonates, 0.05\u2003mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup> in a 1\u2010year\u2010old, 0.06\u2003mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup> in a 5\u2010year\u2010old and 0.05\u2003mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup> in a 12\u2010year\u2010old child. Age\u2010related pharmacodynamic differences that will affect dose and the impact of active metabolites on response are not yet quantified.<\/jats:p>","DOI":"10.1111\/j.1460-9592.2010.03364.x","type":"journal-article","created":{"date-parts":[[2010,8,5]],"date-time":"2010-08-05T19:05:20Z","timestamp":1281035120000},"page":"302-308","source":"Crossref","is-referenced-by-count":72,"title":["A maturation model for midazolam clearance"],"prefix":"10.1111","volume":"21","author":[{"given":"Brian J.","family":"Anderson","sequence":"first","affiliation":[]},{"given":"Peter","family":"Larsson","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2011,2,15]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200847040-00002"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-006-0189-x"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2009.03113.x"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2006.114835"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200645090-00005"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200645070-00004"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.48.113006.094708"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.24.25"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.01589"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9592.2002.00616.x"},{"key":"e_1_2_6_12_2","first-page":"iv","article-title":"The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves","volume":"14","author":"Hill AV","year":"1910","journal-title":"J Physiol"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1177\/00912700122012832"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2004.01374.x"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2004-1915"},{"key":"e_1_2_6_16_2","volume-title":"NONMEM Project Group. 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