Abstract
The aim of this study was to examine the relationship between the pharmacokinetics of daunorubicin (DNR), overexpression of P-glycoprotein (Pgp) and treatment response in acute leukaemia. Twenty-seven patients with acute leukaemia received DNR as part of induction therapy. The plasma and cellular levels of DNR and its metabolite daunorubicinol (DOL) were determined using high-performance liquid chromatography. There were no significant differences between patients who went into complete remission (12/23) compared with those who did not respond for the following pharmacokinetic parameters: DNR and DOL plasma AUC (area under the curve) and DNR plasma half-life and clearance. There was a significant difference in the cellular DNR and DOL AUC between responders and non-responders (P < 0.02). Seven patients were Pgp positive and 18 Pgp negative. There was no correlation between patient response and the presence of Pgp (P > 0.1), nor was there any correlation between the cellular concentration of DNR or DOL and Pgp (P > 0.3). To our knowledge this is the first report examining the relationship between DNR pharmacokinetics, patient response and Pgp expression. Our data indicated that acute leukaemia patients responding to chemotherapy had higher cellular DNR and DOL than non-responders; also, overexpression of Pgp appeared not to be the sole explanation for the lower cellular DNR levels as expected from in vitro studies.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 24 print issues and online access
$259.00 per year
only $10.79 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Galettis, P., Boutagy, J. & Ma, D. Daunorubicin pharmacokinetics and the correlation with P-glycoprotein and response in patients with acute leukaemia. Br J Cancer 70, 324–329 (1994). https://doi.org/10.1038/bjc.1994.301
Issue Date:
DOI: https://doi.org/10.1038/bjc.1994.301
This article is cited by
-
Adjunction of a fish oil emulsion to cytarabine and daunorubicin induction chemotherapy in high-risk AML
Scientific Reports (2022)
-
Population pharmacokinetics of Daunorubicin in adult patients with acute myeloid leukemia
Cancer Chemotherapy and Pharmacology (2016)
-
Carbonyl reductase 1 expression influences daunorubicin metabolism in acute myeloid leukemia
European Journal of Clinical Pharmacology (2012)
-
A phase Ib study of vosaroxin, an anticancer quinolone derivative, in patients with relapsed or refractory acute leukemia
Leukemia (2011)
-
Uptake of anthracyclines in vitro and in vivo in acute myeloid leukemia cells in relation to apoptosis and clinical response
European Journal of Clinical Pharmacology (2009)