Plasma pharmacokinetics and cerebrospinal fluid concentrations of idarubicin and idarubicinol in pediatric leukemia patients: A Childrens Cancer Study Group report

Joel M Reid, Thomas W. Pendergrass, Mark D. Krailo, G. Denman Hammond, Matthew M. Ames

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6525-6528
Number of pages4
JournalCancer Research
Volume50
Issue number20
StatePublished - Oct 15 1990

Fingerprint

Idarubicin
Cerebrospinal Fluid
Leukemia
Pharmacokinetics
Pediatrics
Neoplasms
Appointments and Schedules
Half-Life
idarubicinol
Anthracyclines
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Parents
Recurrence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Plasma pharmacokinetics and cerebrospinal fluid concentrations of idarubicin and idarubicinol in pediatric leukemia patients : A Childrens Cancer Study Group report. / Reid, Joel M; Pendergrass, Thomas W.; Krailo, Mark D.; Hammond, G. Denman; Ames, Matthew M.

In: Cancer Research, Vol. 50, No. 20, 15.10.1990, p. 6525-6528.

Research output: Contribution to journalArticle

Reid, Joel M ; Pendergrass, Thomas W. ; Krailo, Mark D. ; Hammond, G. Denman ; Ames, Matthew M. / Plasma pharmacokinetics and cerebrospinal fluid concentrations of idarubicin and idarubicinol in pediatric leukemia patients : A Childrens Cancer Study Group report. In: Cancer Research. 1990 ; Vol. 50, No. 20. pp. 6525-6528.
@article{b40171ac4b4040b69040cf76c8e3208f,
title = "Plasma pharmacokinetics and cerebrospinal fluid concentrations of idarubicin and idarubicinol in pediatric leukemia patients: A Childrens Cancer Study Group report",
abstract = "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.",
author = "Reid, {Joel M} and Pendergrass, {Thomas W.} and Krailo, {Mark D.} and Hammond, {G. Denman} and Ames, {Matthew M.}",
year = "1990",
month = "10",
day = "15",
language = "English (US)",
volume = "50",
pages = "6525--6528",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "20",

}

TY - JOUR

T1 - Plasma pharmacokinetics and cerebrospinal fluid concentrations of idarubicin and idarubicinol in pediatric leukemia patients

T2 - A Childrens Cancer Study Group report

AU - Reid, Joel M

AU - Pendergrass, Thomas W.

AU - Krailo, Mark D.

AU - Hammond, G. Denman

AU - Ames, Matthew M.

PY - 1990/10/15

Y1 - 1990/10/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0025088877&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025088877&partnerID=8YFLogxK

M3 - Article

C2 - 2208112

AN - SCOPUS:0025088877

VL - 50

SP - 6525

EP - 6528

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 20

ER -