Pharmacokinetics of adriamycin in patients with breast cancer: correlation between pharmacokinetic parameters and clinical short-term response.
The pharmacokinetics of adriamycin was evaluated in the plasma of 12 patients with breast cancer after injection of an i.v. bolus. The patients were suffering from a locally advanced tumor, were free of metastases and had received no prior treatment. They received a chemotherapy consisting in adriamycin (50 mg/m2) on day 1, vincristine (1 mg/m2) on day 2 and methotrexate (6 mg/m2) on days 3, 4 and 5. The response to chemotherapy was assessed as the percentage of reduction of the palpable tumoral mass. Plasma samples were collected at various times after injection of the drug. Adriamycin and its metabolites were extracted using an original column purification technique and were evaluated by high-performance liquid chromatography with fluorometric detection. Pharmacokinetic parameters were calculated with a computer program based upon an algorithm of non-linear function minimization. The three successive half-lives presented little individual variations and were 4.75 min, 0.822 hr and 18.9 hr. On the other hand, the A, B and C parameters were highly scattered. The total plasma clearance of the parent drug ranged from 28.3 to 98.7 1/hr. A highly significant correlation was observed between parameter A and the short-term clinical response. Moreover, a mild correlation exists between the half-life of the 1st phase and the short-term clinical response. We can therefore assume that the efficacy of the drug may be dependent upon its distribution in the organism. Such a relationship may allow the development of new protocols of chemotherapy in order to obtain an optimal distribution of the drug in every patient.
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D004317:Doxorubicin / Q000097:blood* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D014750:Vincristine / Q000627:therapeutic use
D014750:Vincristine; D004317:Doxorubicin; D008727:Methotrexate