Determination of daunorubicin and its main metabolites in plasma, urine and leukaemic cells in patients with acute myeloblastic leukaemia.

The pharmacokinetics of daunorubicin were studied in 3 previously untreated patients with acute myeloblastic leukaemia by simultaneous monitoring of daunorubicin (DNR), daunorubicinol (DOL) and their aglycones in plasma, urine and leukaemic cells. The drug was given as an i.v. infusion in a dose of 1.5 mg/kg body wt. The plasma concentration of daunorubicin declined rapidly after the infusion. The concentration of daunorubicinol exceeded that of the parent compound only 5 min after the end of the infusion. Daunorubicin accumulated extensively in the leukaemic cells and reached concentrations there which exceeded the plasma concentration 400-4000 times. As compared to what was found in plasma, daunorubicinol appeared much slower in the leukaemic cells and the concentration ratio only reached 30-200. The concentration of aglycones was low in the leukaemic cells as well as in plasma. Only about 15% of the administered dose of daunorubicin could be recovered in the urine within 4 days, most of it as daunorubicinol. The results demonstrate that the plasma concentration of daunorubicin and its metabolites provides little information on the drug concentration in the leukaemic cells. Direct determinations of drug concentrations in the leukaemic cells might be of clinical value for optimization of the therapy in acute leukaemia.