{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:31:18Z","timestamp":1761093078126,"version":"build-2065373602"},"reference-count":20,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T00:00:00Z","timestamp":1364947200000},"content-version":"vor","delay-in-days":0,"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":[[2013,7]]},"abstract":"<jats:sec><jats:title>Study Objective<\/jats:title><jats:p>To demonstrate the premise of individualized dosing charts (<jats:styled-content style=\"fixed-case\">IDC<\/jats:styled-content>s) as a clinical\u2010bedside decision\u2010support tool to individualize dosage regimens for drugs in which the interpatient variability is controlled by the pharmacokinetic (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>) behavior of the patient, to calculate the optimal sampling schedule (OSS), which minimizes the number of blood samples per patient. The approach is illustrated with available PK data for gabapentin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Retrospective proof of principles study using gabapentin <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> data from a published clinical trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>Nineteen subjects in a trial designed to uncover the importance of the genetic contributions to variability in gabapentin absorption, renal elimination, and transport; subjects were monitored for 36\u00a0hours after administration of a single dose of gabapentin 400\u00a0mg, and plasma concentrations were determined at 14 time points.<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements and Main Results<\/jats:title><jats:p>When the <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> profiles were different between subjects, the <jats:styled-content style=\"fixed-case\">IDC<\/jats:styled-content>s are dramatically different from each other and from the <jats:styled-content style=\"fixed-case\">IDC<\/jats:styled-content> for an \u201caverage\u201d patient representing the patient population. The dose amount and dosing interval must be adjusted to maximize the probability of staying within the target concentration range. An optimal sampling methodology based on the assumption\u2010free Bayesian approach is used to distinguish the <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> profile of an individual patient from the patient population. In the case of gabapentin, only two optimally selected test blood samples, at 1.5 and 6\u00a0hours after administration of a single doses, were necessary. The average sensitivity and the average specificity of the <jats:styled-content style=\"fixed-case\">OSS<\/jats:styled-content> was 99% and 96%, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">IDC<\/jats:styled-content>s display the risk of a patient violating the target concentration range for any dosage regimen. They can be used as a clinical\u2010bedside decision\u2010support tool in a patient\u2013physician partnership to decide on a dose amount and dosing interval that are medically acceptable while practical and convenient to ensure compliance. By using the assumption\u2010free Bayesian approach and the <jats:styled-content style=\"fixed-case\">OSS<\/jats:styled-content>, the number of samples required from a new patient to individualize the dosage regimen can be reduced significantly while preserving high levels of sensitivity and specificity. Prospective studies are being planned to validate the encouraging results. This approach can be extended to any drug if <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> data and a target concentration range are available for either therapeutic drug monitoring or target concentration intervention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.1267","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T09:49:41Z","timestamp":1364982581000},"page":"727-735","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Validation of a Novel Approach for Dose Individualization in Pharmacotherapy Using Gabapentin in a Proof of Principles Study"],"prefix":"10.1002","volume":"33","author":[{"given":"Gary E.","family":"Blau","sequence":"first","affiliation":[{"name":"School of Chemical Engineering Purdue University West Lafayette Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seza","family":"Orcun","sequence":"additional","affiliation":[{"name":"Seza Orcun Consulting Services West Lafayette Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 M.","family":"La\u00ednez","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering Purdue University West Lafayette Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gintaras V.","family":"Reklaitis","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering Purdue University West Lafayette Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Attaya","family":"Suvannasankha","sequence":"additional","affiliation":[{"name":"Simon Cancer Center Indiana University Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Fausel","sequence":"additional","affiliation":[{"name":"Simon Cancer Center Indiana University Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elias J.","family":"Anaissie","sequence":"additional","affiliation":[{"name":"School of Medicine University of Cincinnati Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,4,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1999.tb00932.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(03)90011-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.280.21.1837"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199346030-00007"},{"key":"e_1_2_7_6_1","first-page":"S17","article-title":"Clinical pharmacokinetics of gabapentin","volume":"44","author":"McLean MJ","year":"1994","journal-title":"Neurology"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(00)00117-0"},{"key":"e_1_2_7_8_1","unstructured":"A Park Davis a Division of Pfizer 2009"},{"key":"e_1_2_7_9_1","unstructured":"ARUP\u2010Laboratory Test Directory.Gabapentin. Available fromhttp:\/\/www.aruplab.com\/guides\/ug\/tests\/0090056.jsp. Accessed March 22 2012."},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4347(95)00081-S"},{"key":"e_1_2_7_11_1","unstructured":"U.S. News Health.Personalized medicine overview. Available fromhttp:\/\/health.usnews.com\/health-conditions\/cancer\/personalized-medicine. Accessed March 22 2012."},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009356572"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008321789"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199310000-00005"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compchemeng.2007.04.008"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/ie801651y"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/ie101610r"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100271"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-4485-6"},{"key":"e_1_2_7_20_1","article-title":"A decomposition strategy for the variational inference of complex systems","author":"La\u00ednez JM","year":"2012","journal-title":"Technometrics"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/73.3.645"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fphar.1267","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.1267","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T10:09:32Z","timestamp":1761041372000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/phar.1267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,3]]},"references-count":20,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2013,7]]}},"alternative-id":["10.1002\/phar.1267"],"URL":"https:\/\/doi.org\/10.1002\/phar.1267","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"type":"print","value":"0277-0008"},{"type":"electronic","value":"1875-9114"}],"subject":[],"published":{"date-parts":[[2013,4,3]]},"assertion":[{"value":"2013-04-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}