Clinical pharmacology of continuous infusion doxorubicin

Fifteen patients were studied during short-term (5 days at 10-15 mg/m2/day) or long-term (5-104 days at 3 mg/m2/day) doxorubicin infusion. Levels of doxorubicin and metabolites in serum and 24-h timed urine collections were determined by high-performance liquid chromatography. Quantifiable anthracycline levels were identified in serum of 5 of 6 patients (6 courses) receiving drug at 10 mg/m2/day. In 5 courses, total anthracycline levels were 10-80 ng/ml, whereas levels as high as 370 ng/ml were observed in a patient with hepatorenal failure. No detectable serum levels of anthracycline were seen in patients receiving long-term doxorubicin therapy. Although analysis of 24-h timed urine collections revealed that doxorubicin was the predominant anthracycline, the extent of urinary elimination showed considerable interpatient variation (1.0-52.5% of the infused dose/24-h period on the short-term protocol and 5.3-57.2%/24-h period on the long-term protocol). Metabolic processing of doxorubicin administered by continuous infusion was found to be similar to that of drug given by bolus administration and showed no change in pattern with time. However, a greater variability in serum and urinary anthracycline levels was seen among patients on infusion schedules than has been noted with bolus drug treatment.