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 (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.
Kuhlmann
O
O
Section of Pharmacokinetics, Department of Pharmacology, Martin Luther University Halle-Wittenberg, Germany.
Hofmann
S
S
Weiss
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000097:blood; D006207:Half-Life; D006454:Hemoglobins / Q000378:metabolism; D015255:Idarubicin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D007261:Infusions, Intra-Arterial; D007958:Leukocyte Count; D008297:Male; D010976:Platelet Count; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence
D000903:Antibiotics, Antineoplastic; D006454:Hemoglobins; C054440:idarubicinol; D015255:Idarubicin; D003630:Daunorubicin