Plasma pharmacokinetics of adriamycin and antipyrine and its relation to the therapeutic and toxic effects.

After a simultaneous administration of adriamycin and antipyrine to 19 tumor patients, the plasma kinetics of both drugs, the therapeutic effect and the reaction to white blood cells were determined. Antipyrine was given orally at a dose of 875 mg, whereas adriamycin was administered by means of intravenous infusion for 20 min at 60 mg/m2. This application was repeated in eight patients after three weeks. Nine patients had a normal liver function. In ten patients, slight increases were found in individual liver function parameters. All patients were free from metastases of the liver and had bilirubin levels within the normal range. Antipyrine followed an open one-compartment model, whereas adriamycin followed an open two-compartment model. In the mean, t1/2 el and Cl tot of antipyrine were found to be 16.1 h and 32.9 ml/min, t1/2 beta and Cl tot of adriamycin were 23.1 h and 877 ml/min. For antipyrine and adriamycin, these parameters varied interindividually by the factors 2.8 and 3.1, respectively. No correlations were found between the liver function parameters, and the kinetic elimination parameters and the areas under the curves of both drugs. However, significant positive correlations were found to exist between t1/2 el antipyrine and t1/2 beta adriamycin and between the areas under the curves of the two drugs. A relationship between the AUC adriamycinol/AUC adriamycin ratio (which was 0.52 in the mean) and the antipyrine elimination rate did not exist. As compared to 12 persons with no response or progression, the seven patients with partial or complete response had a significantly higher AUC and a significantly lower Cl tot of adriamycin. As compared to the patients with elimination half-life values of less than 20 h, five patients with antipyrine elimination half-life values of more than 20 h had a significantly longer adriamycin elimination beta-phase and a stronger depressive effect on the white blood cells. The results obtained suggest that the antipyrine kinetics in patients with normal or slightly impaired liver function is a useful parameter for an assessment of the depression of white blood cells and the dose adjustment for adriamycin.