{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:59:56Z","timestamp":1790045996851,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,6,26]],"date-time":"2015-06-26T00:00:00Z","timestamp":1435276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA015083"],"award-info":[{"award-number":["P30 CA015083"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32 GM08685"],"award-info":[{"award-number":["T32 GM08685"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>The population pharmacokinetic model reported here was developed using data from 2 phase 2 trials of irinotecan for treatment of malignant glioma to quantify the impact of concomitant therapy with enzyme\u2010inducing antiepileptic drugs (EIAEDs) on irinotecan pharmacokinetics. Patients received weekly irinotecan doses of 100 to 400\u2009mg\/m<jats:sup>2<\/jats:sup>, and plasma samples were collected and analyzed for irinotecan and its APC, SN\u201038, and SN\u201038G metabolites. Nonlinear mixed\u2010effects modeling was employed for population pharmacokinetic analysis. Concomitant therapy with phenytoin, phenobarbital, or carbamazepine increased the clearances of irinotecan, SN\u201038, and SN\u201038G but not APC. SN\u201038 clearance was 2\u2010fold higher with concomitant EIAED use, resulting in 40% lower SN\u201038 exposure. Evaluation of additional covariates revealed no clinically relevant effects of sex or concomitant corticosteroid use. The population pharmacokinetic model suggests that a 1.7\u2010fold increase in irinotecan dose may compensate for decreases in SN\u201038 exposure in the presence of concomitant EIAEDs. Although slightly more conservative, this dose adjustment is consistent with those recommended based on increases in the maximally tolerated dose for malignant glioma patients receiving EIAEDs and may be an appropriate starting point for further investigation when extrapolating to other cancer types or alternative regimens.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcph.543","type":"journal-article","created":{"date-parts":[[2015,5,14]],"date-time":"2015-05-14T23:42:44Z","timestamp":1431646964000},"page":"1303-1312","source":"Crossref","is-referenced-by-count":24,"title":["Quantification of the impact of enzyme\u2010inducing antiepileptic drugs on irinotecan pharmacokinetics and SN\u201038 exposure"],"prefix":"10.1002","volume":"55","author":[{"given":"Alexander K.","family":"Berg","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Upsher\u2010Smith Laboratories Inc. Maple Grove MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan C.","family":"Buckner","sequence":"additional","affiliation":[{"name":"Department of Oncology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evanthia","family":"Galanis","sequence":"additional","affiliation":[{"name":"Department of Oncology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt A.","family":"Jaeckle","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Jacksonville MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew M.","family":"Ames","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel M.","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Oncology Mayo Clinic Rochester MN USA"},{"name":"Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568009023333890"},{"issue":"8","key":"e_1_2_7_3_1","first-page":"1261","article-title":"Pharmacokinetic interrelationships of irinotecan (CPT\u201011) and its three major plasma metabolites in patients enrolled in phase I\/II trials","volume":"3","author":"Rivory LP","year":"1997","journal-title":"Clin Cancer Res."},{"issue":"16","key":"e_1_2_7_4_1","first-page":"4187","article-title":"Intracellular roles of SN\u201038, a metabolite of the camptothecin derivative CPT\u201011, in the antitumor effect of CPT\u201011","volume":"51","author":"Kawato Y","year":"1991","journal-title":"Cancer Res."},{"issue":"5","key":"e_1_2_7_5_1","first-page":"2012","article-title":"Metabolism of irinotecan (CPT\u201011) by CYP3A4 and CYP3A5 in humans","volume":"6","author":"Santos A","year":"2000","journal-title":"Clin Cancer Res."},{"key":"e_1_2_7_6_1","unstructured":"Irinotecan.DRUGDEX\u00ae System[Internet database]. Greenwood Village CO: Thomson Reuters (Healthcare) Inc."},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152010794479825"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1215\/15228517-2008-075"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.108.020602"},{"key":"e_1_2_7_10_1","first-page":"521","volume-title":"Goodman and Gilman's The Pharmacological Basis of Therapeutics","author":"McNamara JO.","year":"2001"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-006-9193-2"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-008-9749-4"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-009-0103-2"},{"issue":"8","key":"e_1_2_7_14_1","first-page":"2940","article-title":"Phase I clinical and pharmacokinetic study of irinotecan in adults with recurrent malignant glioma","volume":"9","author":"Gilbert MR","year":"2003","journal-title":"Clin Cancer Res."},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.5.1516"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0874"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1215\/S1152851703000292"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1215\/S1152851703000498"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21316"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.2440"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.129502"},{"issue":"6","key":"e_1_2_7_22_1","first-page":"1613","article-title":"A limited sampling strategy to estimate the pharmacokinetic parameters of irinotecan and its active metabolite, SN\u201038, in patients with metastatic digestive cancer receiving the FOLFIRI regimen","volume":"18","author":"Poujol S","year":"2007","journal-title":"Oncol Rep."},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.63"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-008-0692-z"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.11.073"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-008-0769-8"},{"issue":"2","key":"e_1_2_7_27_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1093\/oxfordjournals.annonc.a059109","article-title":"Population pharmacokinetics and pharmacodynamics of irinotecan (CPT\u201011) and active metabolite SN\u201038 during phase I trials","volume":"6","author":"Chabot GG","year":"1995","journal-title":"Ann Oncol."},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181bbfeca"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2005.04.005"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.2307\/1390807"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-2607(98)00067-4"},{"key":"e_1_2_7_32_1","unstructured":"BauerRJ.Introduction to NONMEN 7. In:NONMEN Users Guide2009. Ellicott City MD: ICON Development Solutions."},{"key":"e_1_2_7_33_1","unstructured":"BonatePL.Pharmacokinetics Modeling and Simulation. Springer;2011."},{"key":"e_1_2_7_34_1","doi-asserted-by":"crossref","unstructured":"SavicRM KarlssonMO.Importance of shrinkage in empirical bayes estimates for diagnostics: problems and solutions.AAPS. J.2009;11(3):558\u2013569.","DOI":"10.1208\/s12248-009-9133-0"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389200043335397"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.026989"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2010.04.034"},{"key":"e_1_2_7_38_1","unstructured":"CAMPTOSAR\u00aeIrinotecan hydrochloride injection solution [package insert]. New York: Pfizer Inc.;2014."},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2000.110215"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2007.12.003"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70103-5"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcph.543","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.543","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T14:46:48Z","timestamp":1696603608000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.543"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,26]]},"references-count":40,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["10.1002\/jcph.543"],"URL":"https:\/\/doi.org\/10.1002\/jcph.543","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,26]]}}}