Investigations on the dose-dependent pharmacokinetics of adriamycin and its metabolites.

Four tumor patients with a normal liver function were each given twice 30 mg/m2 adriamycin (ADR) and then once 70 mg/m2 ADR in the form of 3-min intravenous bolus injections at three-week intervals. In addition to the first and third ADR administrations, the patients were each given p.o. 875 mg of antipyrine. During the six-week study period, the kinetics of antipyrine displayed a high degree of intra-individual constancy. Its CL varied between 75 and 119 percent intra-individually. The kinetic parameters of CL, AUC/dose, VDss, MRT and t1/2 gamma of ADR did not differ between dosages of 30 and 70 mg/m2. The ADR-dose-standardized AUC10-40 min of adriamycinol (ADR-OH), its concentration time product at the times of its highest concentration in plasma, did not display any dependence upon the ADR dose. The AUCADR-OH/dose quotient, however, was found to be significantly higher (p less than 0.05) at 70 mg/m2 than at 30 mg/m2. The MTR and the t1/2z of ADR-OH showed a trend towards prolongation at 70 mg/m2. The ADR-dose-standardized AUC of the aglycones showed no dependence upon the ADR dose while the ADR-dose-standardized AUC10-40 min of the aglycones was significantly lower at a high ADR dose (p less than 0.05) than at a small ADR dose. The results suggest that in the ADR dose range studied the ADR pharmacokinetics is dose-independent and linear, and the rate at which ADR-OH, its main metabolite is formed, is also dose-independent. In contrast, the elimination of ADR-OH seems to be capacity-limited.(ABSTRACT TRUNCATED AT 250 WORDS)