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Higher plasma but not intracellular concentrations after infusion with liposomal daunorubicin compared with conventional daunorubicin in adult acute myeloid leukemia
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2007 (English)In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 29, no 5, p. 626-631Article in journal (Refereed) Published
Abstract [en]

To investigate the plasma and intracellular pharmacokinetics of liposomal daunorubicin (DaunoXome) in comparison with conventional daunorubicin, 14 patients aged 28 to 60 years with newly diagnosed acute myeloid leukemia were treated for 1 day with DaunoXome (50 mg/m) and for 2 days with daunorubicin (50 mg/m) with concomitant Ara-C (7 days, 200 mg/m, continuous IV). Eleven of the 14 patients entered complete remission; 9 are still alive. Pharmacokinetic profiles were obtained by blood sampling at appropriate intervals on days 1 to 4. Daunorubicin and daunorubicinol concentrations in plasma and in peripheral leukemic blast cells were measured by high-performance liquid chromatography. Following liposomal daunorubicin administration, the peak values and plasma area under the curve (AUC) were more than 100 times higher than after administration of conventional daunorubicin (AUC, 176 vs. 0.98 micromol/L x hour), but the intracellular AUCs were comparable (759 vs. 715 micromol/L x hour). Intracellular concentrations after DaunoXome peaked later and half as high as after daunorubicin. After DaunoXome versus daunorubicin, plasma clearance was 0.001 versus 0.4 micromol/h, respectively. The volume of distribution was 5.5 L for DaunoXome, versus 3640 L for daunorubicin, indicating low tissue affinity for the liposomal formulation. The authors conclude that liposomal daunorubicin, DaunoXome, yields 2-log higher plasma concentrations but similar intracellular concentrations of daunorubicin and its metabolite daunorubicinol than does free daunorubicin.

Place, publisher, year, edition, pages
New York: Raven P. , 2007. Vol. 29, no 5, p. 626-631
National Category
Medical and Health Sciences Cancer and Oncology
Research subject
Medicine
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URN: urn:nbn:se:oru:diva-11570DOI: 10.1097/FTD.0b013e318156e938PubMedID: 17898654OAI: oai:DiVA.org:oru-11570DiVA, id: diva2:343447
Available from: 2010-08-13 Created: 2010-08-13 Last updated: 2017-12-12Bibliographically approved

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Tidefelt, Ulf

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