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Doxorubicin pharmacokinetics is correlated to the effect of induction therapy in children with acute myeloid leukemia
Uppsala.
Uppsala.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
Stockholm.
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2006 (English)In: Anti-Cancer Drugs, ISSN 0959-4973, E-ISSN 1473-5741, Vol. 17, no 4, 385-392 p.Article in journal (Refereed) Published
Abstract [en]

We studied the pharmacokinetics of doxorubicin in 41 children treated for newly diagnosed acute myeloid leukemia. Doxorubicin, 75 mg/m body surface area, was administered by constant i.v. infusion over 8 h. Four children with Down's syndrome (DS), 1.2-2.3 years old, had a median total body clearance of 523 ml/min/m. The median clearance in non-DS children, 0.6-1.8 years old (n=4) and 2.5-17.7 years old (n=33), was 446 and 538 ml/min/m, respectively. Patients who went into complete remission (CR) after induction therapy had a significantly higher median plasma concentration of doxorubicin than those who did not, 249 compared with 180 ng/ml, respectively (P=0.036, analysis restricted to non-DS patients). Doxorubicin plasma concentration was an independent factor for CR, both in univariate (P=0.031) and multivariate analysis including sex, age and white blood cell count at diagnosis (P=0.021). Patients who reached CR had a significantly lower doxorubicin clearance than those who did not, 513 and 657 ml/min/m, respectively (P=0.017). In conclusion, doxorubicin plasma concentration and total body clearance during up-front treatment were correlated to the effect of induction therapy. Prospective studies should be performed to confirm the concentration-effect relationship and explore the possibility of therapeutic monitoring. © 2006 Lippincott Williams & Wilkins.

Place, publisher, year, edition, pages
2006. Vol. 17, no 4, 385-392 p.
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Medical and Health Sciences
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URN: urn:nbn:se:liu:diva-37107DOI: 10.1097/01.cad.0000198911.98442.16Local ID: 33706OAI: oai:DiVA.org:liu-37107DiVA: diva2:257956
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13

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Peterson, Curt

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