Pharmacokinetics and toxicity of idarubicin in the rat

This study was designed to examine the pharmacokinetics and toxicity of idarubicin (IDA) in rats. In two groups of rats IDA was infused either into the V. iugularis interna or into the A. carotis communis, respectively. The venous plasma concentration of IDA and its primary metabolite idarubicinol (...

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Bibliographic Details
Published in:European journal of drug metabolism and pharmacokinetics 2001-10, Vol.26 (4), p.215-219
Main Authors: KUHLMANN, Olaf, HOFMANN, Stefan, WEISS, Michael
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antineoplastic - administration & dosage
Antibiotics, Antineoplastic - pharmacokinetics
Antibiotics, Antineoplastic - toxicity
Antineoplastic agents
Biological and medical sciences
Chemotherapy
Chromatography, High Pressure Liquid
Daunorubicin - analogs & derivatives
Daunorubicin - blood
Drug toxicity and drugs side effects treatment
Half-Life
Hemoglobins - metabolism
Idarubicin - administration & dosage
Idarubicin - pharmacokinetics
Idarubicin - toxicity
Infusions, Intra-Arterial
Leukocyte Count
Male
Medical sciences
Pharmacology. Drug treatments
Platelet Count
Rats
Rats, Wistar
Spectrometry, Fluorescence
Toxicity: blood
Citations: Items that this one cites
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Summary:This study was designed to examine the pharmacokinetics and toxicity of idarubicin (IDA) in rats. In two groups of rats IDA was infused either into the V. iugularis interna or into the A. carotis communis, respectively. The venous plasma concentration of IDA and its primary metabolite idarubicinol (IDOL) were measured up to 48 hours by high-performance liquid chromatography (HPLC) with fluorescence detection. The weights of the rats and the levels of haemoglobin, leukocytes, and thrombocytes were recorded. The plasma concentration-time data were analysed, assuming a biexponential disposition curve, both by the traditional (two-stage) method and by population pharmacokinetic modelling. The basic pharmacokinetic parameters clearance (CL = 27.0 ml min(-1)), mean disposition residence time (MDRT = 519.2 min), and volume of distribution at steady state (Vss = 12.51) were estimated for IDA. The mean residence time (MRT) of the generated IDOL was 2982.5 min. No significant differences between pre- and postpulmonal injection were found in the pharmacokinetics and pharmacodynamics of IDA. The mean survival time of 13.3 days is attributed to a severe myelosuppression.
ISSN:0378-7966
2107-0180
DOI:10.1007/BF03226374