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Repeated daunomycin administration in rats

Pharmacokinetics and bone marrow toxicity

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In the experiments described here, rats received three IV bolus injections (7.5 mg/kg) of daunomycin. The plasma data obtained after a single IV injection could be described by a two-compartment open model with t1/2α and t1/2β values of 18.4 and 472.1 min. Of the tissues, the lungs contained the most daunomycin per gram of tissue, followed by the kidneys, liver, heart, and spleen. Daunomycinol was the main metabolic product and no substantial differences were found in daunomycinol content among the different organs. For all tissues and plasma, higher drug concentration values than would be expected on the basis of accumulation alone were observed after the second but not after the third injection. The cumulative urine excretion of daunomycin and daunomycinol remained essentially unchanged after one, two, and three daunomycin injections. However, the cumulative bile excretion incrased after repeated daunomycin administration. The experiments in which the myelotoxicity was assessed by CFU-S survival after daunomycin treatment showed that three successive daunomycin administrations lead to a proportional reduction in stem cells.

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Correspondence to Kees Nooter.

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Nooter, K., Sonneveld, P., Deurloo, J. et al. Repeated daunomycin administration in rats. Cancer Chemother. Pharmacol. 12, 187–189 (1984). https://doi.org/10.1007/BF00256543

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  • Stem Cell
  • Cancer Research
  • Drug Concentration
  • Open Model
  • Urine Excretion