This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Reid, J. M. Articles by Ames, M. M. Search for Related Content PubMed PubMed Citation Articles by Reid, J. M. Articles by Ames, M. M.

Plasma Pharmacokinetics and Cerebrospinal Fluid Concentrations of Idarubicin and Idarubicinol in Pediatric Leukemia Patients: A Childrens Cancer Study Group Report¹

Division of Developmental Oncology Research, Department of Oncology, Mayo Clinic and Foundation, Rochester, Minnesota 55905 [J. M. R., M. M. A.]; Division of Hematology/Oncology, Department of Pediatrics, University of Washington (and Children's Hospital and Medical Center), Seattle, Washington 98105 [T. W. P.]; and University of Southern California School of Medicine, Los Angeles, California 91101 [M. D. K., G. D. H.]

Idarubicin (4-demethoxydaunomycin) is an anthracycline analogue with striking in vitro and in vivo activity against murine leukemias. Based on activity in adults with acute lymphoblastic leukemia, the Childrens Cancer Study Group initiated studies to evaluate idarubicin in children with leukemia in second or subsequent relapses. As part of those studies, we have characterized the plasma pharmacokinetics of idarubicin and the major circulating metabolite idarubicinol in 21 patients. Idarubicin plasma elimination was described by a three-compartment open model following i.v. infusion (10–15 mg/m²) on a schedule of weekly for 3 weeks and on a schedule of daily for 3 days every 3 weeks (total dose, 30–45 mg/m²). There was substantial variability in idarubicin elimination among patients, but no indication of dose-dependent or of schedule-dependent changes in pharmacokinetic parameters. The mean terminal half-life, total body clearance, and steady state volume of distribution were 17.6 h, 679 ml/min/m², and 562 l/m², respectively. Idarubicinol elimination was prolonged compared to that of the parent drug with a terminal half-life of 56.8 h. This metabolite clearly accumulated in plasma during the 3 days of treatment on the schedule of daily for 3 days. Urinary recoveries (48 h) of idarubicin and idarubicinol after a single dose of idarubicin were 2.4 and 10.1%, respectively. Idarubicin was detected in 2 of 21 cerebrospinal fluid samples obtained 18–30 h after administration. In marked contrast, idarubicinol was detected in 20 of those 21 samples. Concentrations in the 20 samples varied from 0.22–1.05 ng/ml with a mean value of 0.51 ng/ml.

¹ This work is supported in part by the National Cancer Institute, DHHS Grant CA 28882, and Adria Laboratories.

² To whom requests for reprints should be addressed, at 200 First Street, S.W., Rochester, MN 55905.

Received 3/29/90. Accepted 7/13/90.

This article has been cited by other articles:

				B. J. Lange, F. O. Smith, J. Feusner, D. R. Barnard, P. Dinndorf, S. Feig, N. A. Heerema, C. Arndt, R. J. Arceci, N. Seibel, et al. Outcomes in CCG-2961, a Children's Oncology Group Phase 3 Trial for untreated pediatric acute myeloid leukemia: a report from the Children's Oncology Group Blood, February 1, 2008; 111(3): 1044 - 1053. [Abstract] [Full Text] [PDF]

				L. L. Muldoon, C. Soussain, K. Jahnke, C. Johanson, T. Siegal, Q. R. Smith, W. A. Hall, K. Hynynen, P. D. Senter, D. M. Peereboom, et al. Chemotherapy Delivery Issues in Central Nervous System Malignancy: A Reality Check J. Clin. Oncol., June 1, 2007; 25(16): 2295 - 2305. [Abstract] [Full Text] [PDF]

				B. J. Lange, P. Dinndorf, F. O. Smith, C. Arndt, D. Barnard, S. Feig, J. Feusner, N. Seibel, M. Weiman, R. Aplenc, et al. Pilot Study of Idarubicin-Based Intensive-Timing Induction Therapy for Children With Previously Untreated Acute Myeloid Leukemia: Children's Cancer Group Study 2941 J. Clin. Oncol., January 1, 2004; 22(1): 150 - 156. [Abstract] [Full Text] [PDF]

				T. Nakanishi, L. A. Doyle, B. Hassel, Y. Wei, K. S. Bauer, S. Wu, D. W. Pumplin, H.-B. Fang, and D. D. Ross Functional Characterization of Human Breast Cancer Resistance Protein (BCRP, ABCG2) Expressed in the Oocytes of Xenopus laevis Mol. Pharmacol., December 1, 2003; 64(6): 1452 - 1462. [Abstract] [Full Text] [PDF]

				Z. E. Dreyer, R. P. Kadota, C. F. Stewart, H. S. Friedman, D. H. Mahoney, L. E. Kun, C. W. McCluggage, P. C. Burger, J. Kepner, and R. L. Heideman Phase 2 study of idarubicin in pediatric brain tumors: Pediatric Oncology Group study POG 9237 Neuro-oncol, October 1, 2003; 5(4): 261 - 267. [Abstract] [PDF]

				G. L. Chantada, A. Fandino, G. Mato, and S. Casak Phase II Window of Idarubicin in Children With Extraocular Retinoblastoma J. Clin. Oncol., June 1, 1999; 17(6): 1847 - 1847. [Abstract] [Full Text] [PDF]