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Here a novel methodology is presented to make such estimates using a standard serum paracetamol measurement and a computational framework.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The core component of the computational framework was a physiologically\u2010based pharmacokinetic (PBPK) model developed and evaluated using an extensive set of human PK data. Bayesian inference was used for parameter and dose estimation, allowing the incorporation of inter\u2010study variability, and facilitating the calculation of uncertainty in model outputs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Simulations of paracetamol time course concentrations in the blood were in close agreement with experimental data under a wide range of dosing conditions. Also, predictions of administered dose showed good agreement with a large collection of clinical and emergency setting PK data over a broad dose range. In addition to dose estimation, the platform was applied for the determination of optimal blood sampling times for dose reconstruction and quantitation of the potential role of paracetamol conjugate measurement on dose estimation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Current therapies for paracetamol overdose rely on a generic methodology involving the use of a clinical nomogram. By using the computational framework developed in this study, serum sample data, and the individual patient's anthropometric and physiological information, personalized serum and liver pharmacokinetic profiles and dose estimate could be generated to help inform an individualized overdose treatment and follow\u2010up plan.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12796","type":"journal-article","created":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T17:48:16Z","timestamp":1444153696000},"page":"634-645","source":"Crossref","is-referenced-by-count":14,"title":["A novel approach for estimating ingested dose associated with paracetamol overdose"],"prefix":"10.1111","volume":"81","author":[{"given":"Todd J.","family":"Zurlinden","sequence":"first","affiliation":[{"name":"Department of Chemical and Biological Engineering Colorado State University Fort Collins Colorado 80523\u20101370"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kennon","family":"Heard","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine University of Colorado School of Medicine 12401 E. 17th Avenue Campus Box B\u2010215 Aurora CO 80045"},{"name":"Rocky Mountain Poison and Drug Center Denver CO 80204"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad","family":"Reisfeld","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering Colorado State University Fort Collins Colorado 80523\u20101370"},{"name":"School of Biomedical Engineering Colorado State University Fort Collins Colorado 80523\u20101376 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050291"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2710.2004.00626.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1986.tb02953.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200730060-00002"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0b013e31818a3854"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.20735"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v68n1017"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1081\/CLT-120002882"},{"key":"e_1_2_9_10_1","doi-asserted-by":"crossref","unstructured":"MohamedAB ZaibiG KachouriA. 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