{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:09:12Z","timestamp":1793156952169,"version":"4.5.0"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Fentanyl pharmacokinetic and pharmacodynamic data are limited in mechanically ventilated children. This study aimed to assess the fentanyl pharmacokinetics (PK), the sedation outcome, and the development of tolerance in children receiving fentanyl continuous infusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study included children admitted to the pediatric or cardiovascular intensive care unit between January 1 and October 31, 2016, who were &gt;30\u00a0days to &lt;18\u00a0years of age, receiving ventilatory support via endotracheal tube or tracheostomy, and receiving a fentanyl infusion. Population PK analysis was performed using a nonlinear mixed\u2010effects model. The relationship between initial sedation outcome using State Behavioral Scale (SBS) and fentanyl exposure was assessed, and the observations consistent with tolerance were described.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seventeen children, with a median age of 0.83\u00a0years (range: 0.1\u201312) and weight of 8.7\u00a0kg (range: 3.4\u201352), were included. The fentanyl PK was adequately described by a weight\u2010based allometry model with the power of 0.75 for clearance (CL=89.8 L\/hr\/70\u00a0kg) and distributional CL, and 1 for volumes of distribution. In infants &lt;6.6\u00a0months, age was an additional factor for CL (31.4 L\/h\/70\u00a0kg) to account for age\u2010related maturation. Seven of twelve nonparalyzed patients achieved goal sedation, defined as &gt;80% of SBS scores \u22640 per 24\u00a0h, on the first day of fentanyl infusion with a median plasma concentration of 1.29\u00a0ng\/ml (interquartile range: 0.78\u20132.05). Eight of the nine tolerant patients developed tolerance within a day of reaching goal sedation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Different weight\u2010based fentanyl dosing rates may be required for infants and children of different ages to achieve similar plasma concentrations. Using SBS scores may guide the dosing titration of fentanyl that resulted in plasma concentrations within the therapeutic range of 1\u20133\u00a0ng\/ml. For those who developed tolerance to fentanyl and\/or a sedative, it was noted one day after goal sedation was achieved.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2515","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T03:15:20Z","timestamp":1613704520000},"page":"359-369","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Analysis of fentanyl pharmacokinetics, and its sedative effects and tolerance in critically ill children"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0070-0798","authenticated-orcid":false,"given":"Sin Yin","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Clinical and Administrative Sciences University of Oklahoma College of Pharmacy Oklahoma City OK USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie L.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Clinical and Administrative Sciences University of Oklahoma College of Pharmacy Oklahoma City OK USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Henry","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Oklahoma College of Medicine Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Heltsley","sequence":"additional","affiliation":[{"name":"Aegis Sciences Corporation Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukyung","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Oklahoma College of Pharmacy Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3022-4403","authenticated-orcid":false,"given":"Peter N.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Clinical and Administrative Sciences University of Oklahoma College of Pharmacy Oklahoma City OK USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/PCC.0b013e318253c80e"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.PCC.0000144710.13710.2E"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.5409\/wjcp.v6.i2.110"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199307000-00012"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2018.1432595"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.14.7744"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1515\/jtim-2016-0016"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.PCC.0000160659.40315.B3"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-0489"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/NCI.0b013e31826b4dea"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.PCC.0000200955.40962.38"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000001347"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.23574"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-017-0569-6"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.169"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12096"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199937060-00004"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12903"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00773-1"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1980.138"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199101000-00010"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-198906000-00008"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)22695-7"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200409000-00008"},{"key":"e_1_2_8_26_1","unstructured":"Fentanyl.Lexicomp Online Lexi\u2010Drugs Online Hudson Ohio: Wolters Kluwer Clinical Drug Information Inc.;2013; 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