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Through the use of fluorescence assay methods, the plasma levels, urinary excretion, and tissue levels of daunomycin and its fluorescent metabolites were determined in patients treated with this drug for disseminated solid malignancies. The patients received daunomycin in a single rapid intravenous dose at 80 mg. per square meter and 120 mg. per square meter. Fluorescence studies showed the short plasma half‐life to be 0.75 hours, the long plasma half‐life to be 55 hours, the apparent volume of distribution to be ab out 1,000 L., and the relative volume of distribution to be 580 L. per square meter. Drug and fluorescent metabolites in urine averaged 13 to 14 per cent of the total dosage in 7 days. Tritiated daunomycin was used, but isotopic assay produced values different from those with fluorescence assay. These were interpreted to be the result of tritium exchange or metabolism of the daunomycin. Daunomycin fluorescence was detected in autopsy specimens 16 and 19 hours after administration, with the highest levels in kidney, spleen, liver, and lung. The fluorescent species extracted from both plasma and urine consisted predominantly of daunomycin (D1) and daunomycin metabolite (D2), although small amounts of the aglycones were detected. It is proposed that, because of the long half‐life of daunomycin, the current treatment schedule be revised to a single intravenous dose.
Alberts et al. (Fri,) studied this question.