{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:30:22Z","timestamp":1787495422906,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Topotecan, an antitumor drug with systemic exposure (SE)\u2010dependent activity against many pediatric tumors has wide interpatient pharmacokinetic variability, making it challenging to attain the desired topotecan SE. The study objectives were to update our topotecan population pharmacokinetic model, to evaluate the feasibility of determining individual topotecan clearance using a single blood sample, and to apply this approach to topotecan data from a neuroblastoma trial to explore exposure\u2013response relationships.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedure<\/jats:title>\n                    <jats:p>Our previous population pharmacokinetic and covariate model was updated using data from 13 clinical pediatric studies. A simulation\u2010based Bayesian analysis was performed to determine if a single blood sample could be sufficient to estimate individual topotecan clearance. Following the Bayesian approach, single pharmacokinetic samples collected from a Children's Oncology Group Phase III clinical trial (ANBL0532; NCT0056767) were analyzed to estimate individual topotecan SE. Associations between topotecan SE and toxicity or early response were then evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The updated population model included the impact of patient body surface area (BSA), age, and renal function on topotecan clearance. The Bayesian analysis with the updated model and single plasma samples showed that individual topotecan clearance values were estimated with good precision (mean absolute prediction error \u226416.2%) and low bias (mean prediction error \u22647.2%). Using the same approach, topotecan SE was derived in patients from ANBL0532. The exposure\u2013response analysis showed an increased early response after concomitant cyclophosphamide and topotecan up to a topotecan SE of 45\u00a0h\u00a0ng\/mL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A simple single\u2010sample approach during topotecan therapy could guide dosing for patients, resulting in more patients reaching target attainment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.30658","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T05:28:10Z","timestamp":1693805290000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Topotecan clearance based on a single sample and a population pharmacokinetic model: Application to a pediatric high\u2010risk neuroblastoma clinical trial"],"prefix":"10.1002","volume":"70","author":[{"given":"Olivia","family":"Campagne","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianrong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlene","family":"Naranjo","sequence":"additional","affiliation":[{"name":"Children's Oncology Group Statistics and Data Center University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinay M.","family":"Daryani","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5019-0699","authenticated-orcid":false,"given":"Amar J.","family":"Gajjar","sequence":"additional","affiliation":[{"name":"Department of Oncology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie R.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Oncology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1546-9720","authenticated-orcid":false,"given":"Clinton F.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"1431","article-title":"Camptothecins: from bench research to hospital wards","volume":"54","author":"Potmesil M","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00685553"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/90.7.505"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00173681"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-199611000-00004"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.08.174"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2001.19.15.3463"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00686188"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-9084(98)80009-6"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27578"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1376"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1243"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1994.12.9.1946"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-005-0062-z"},{"key":"e_1_2_9_16_1","unstructured":"Weight\u2010for\u2010age charts 2 to 20 years LMS parameters and selected smoothed weight percentiles in kilograms by sex and age.CDC (Centers for Disease Control and Prevention);2013. 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