{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:23:03Z","timestamp":1789017783876,"version":"build-2803163510"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,9,3]],"date-time":"2009-09-03T00:00:00Z","timestamp":1251936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002347","name":"German Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"crossref","award":["1EC0401"],"award-info":[{"award-number":["1EC0401"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>There is an extreme paucity of pharmacokinetic data for anticancer agents in infants. Therefore, we aimed at characterizing the pharmacokinetics for daunorubicin in infants and examined their relationship to age, body weight, and body surface area.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Leukemia patients treated according to the Interfant 99 protocol received 30\u2009mg\/m<jats:sup>2<\/jats:sup> daunorubicin, with dose reduction to 3\/4 for patients 6\u201312 months old and 2\/3 for patients &lt;6 months, respectively. Plasma samples from 21 patients (aged 0.05\u20131.88 years) were collected and analyzed for daunorubicin and daunorubicinol. Samples from 12 children (age 1.6\u201318.8 years), who received daunorubicin in an earlier investigation, were used for pharmacokinetic model building using the software NONMEM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Plasma concentration time profiles could be described using a two compartment model. Daunorubicin clearance was 43.9\u2009L\u2009hr<jats:sup>\u22121<\/jats:sup>\u2009m<jats:sup>\u22122<\/jats:sup>\u2009\u00b1\u200965% and central volume of distribution 16.4\u2009L\u2009m<jats:sup>\u22122<\/jats:sup>\u2009\u00b1\u200946%, whereas apparent clearance of daunorubicinol was 19.1\u2009L\u2009hr<jats:sup>\u22121<\/jats:sup>\u2009m<jats:sup>\u22122<\/jats:sup>\u2009\u00b1\u200932% and apparent volume of distribution 228\u2009L\u2009m<jats:sup>\u22122<\/jats:sup>\u2009\u00b1\u200980% (mean\u2009\u00b1\u2009interindividual variability). No age\u2010dependency in any of the BSA\u2010normalized pharmacokinetic parameters was observed. Consequently, due to the empirical dose reduction in infants the overall exposure to daunorubicinol in infants was smaller than would be expected from older children. Patients aged &lt;6 months experienced more infections in the induction phase than the group aged 6\u201312 months at diagnosis. Other toxicities were similar in both groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We observed no indication of an age\u2010dependency in the pharmacokinetics of daunorubicin. Pediatr Blood Cancer 2010;54:355\u2013360. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.22266","type":"journal-article","created":{"date-parts":[[2009,9,3]],"date-time":"2009-09-03T15:57:11Z","timestamp":1251993431000},"page":"355-360","source":"Crossref","is-referenced-by-count":21,"title":["Pharmacokinetics of daunorubicin and daunorubicinol in infants with leukemia treated in the interfant 99 protocol"],"prefix":"10.1002","volume":"54","author":[{"given":"Georg","family":"Hempel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary V.","family":"Relling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"de Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Stary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"De Lorenzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Valsecchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Barisone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Boos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"Pieters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,9,3]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdf167"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1997.15.1.61"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199506293322602"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(01)00185-2"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20463"},{"key":"e_1_2_6_7_2","first-page":"219","article-title":"Pharmacokinetics and metabolism of anthracyclines","volume":"17","author":"Robert J","year":"1993","journal-title":"Cancer Surv"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1993.1023"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.2001.880505.x"},{"key":"e_1_2_6_10_2","first-page":"S23","article-title":"Disposition of antineoplastic agents in the very young child","volume":"18","author":"McLeod HL","year":"1992","journal-title":"Br J Cancer Suppl"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1995.13.12.2954"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61126-X"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02086146"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012299115260"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(00)84177-8"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-004-0775-4"},{"key":"e_1_2_6_17_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s00280-002-0542-3","article-title":"A population pharmacokinetic model for doxorubicin and doxorubicinol in the presence of a novel MDR modulator, zosuquidar trihydrochloride (LY335979)","volume":"51","author":"Callies S","year":"2003","journal-title":"Cancer Chemother Pharmacol"},{"key":"e_1_2_6_18_2","first-page":"283","article-title":"Pharmacokinetics of daunorubicin as a determinant of response in acute myeloid leukemia","volume":"30","author":"Kokenberg E","year":"1987","journal-title":"Haematol Blood Transfus"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199733050-00001"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2005.05909.x"}],"container-title":["Pediatric Blood &amp; 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