EARLY PHASE PHARMACOKINETICS OF DOXORUBICIN (ADRIAMYCIN) IN PLASMA OF CANCER-PATIENTS DURING SINGLE-DRUG OR MULTIPLE-DRUG THERAPY

Abstract

Doxorubicin (adriamycin [AM]) was measured in plasma in the early distributive phase in 26 patients with different solid tumors. Pharmacokinetic parameters were calculated during 1st and/or subsequent courses of AM injected i.v. at doses from 40-60 mg/m2 alone or with other antineoplastic agents. A fluorimetric technique was employed to determine AM equivalents; the reduced metabolite adriamycinol was quantitated by scanning fluorescence after separation in TLC. After repeated AM treatments the individual variability in pharmacokinetic parameters of the drug did not appear to be affected by the length of treatment. When the same patient was given different AM doses over a certain period, some degree of dose dependence was seen only in the area under the curve and extrapolated plasma drug concentration at Time 0. A narrow range of AM doses gave pharmacokinetic values differing from one patient to another. After repeated AM treatments, adriamycinol levels became lower, suggesting a reduced metabolism of the parent compound or increased excretion of the reduced metabolite.