Abstract
The pharmacokinetic evaluation of daunorubicin and its principal human metabolites, daunorubicinol and two previously unidentified metabolites, has provided information concerning the in vivo metabolism of daunorubicin in patients with acute non lymphocytic leukemia. Daunorubicinol was the maior fluorescent material present in plasma and urine and was a significant metabolite in the tissues. For 8 patients, the mean plasma half‐lifes of daunorubicin and daunorubicinol were 18.5 ± 4.86 hours S.D. and 26.7 ± 12.8 hours S.D., respectively. In 4 of these patients the plasma half‐lifes of daunorubicin and daunorubicinol were equal, indicating a variability of the pharmacokinetics in different individuals. These observations together with the earlier demonstration of increased production of daunorubicinol in vitro by leukemic leukocytes from responding patients indicate a significant role for daunorubicinol in the pharmacodynamics of daunorubicin therapy. One of the new metabolites, D5, was the predominant fluorescent material in human heart.
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