[Pharmacokinetic study of mitoxantrone]

The pharmacokinetics of mitoxantrone, an anthraquinone antitumor agent, were cooperatively investigated at 5 institutions including 4 patients with breast cancer and 3 patients with malignant lymphoma. A single dose of 10 mg/m2 was intravenously infused into 5 patients, and a 5-day schedule of repeated 4.2 mg/m2 or 3 mg/m2 was given to each of 2 patients. With single administration, the blood concentrations showed that the half-life for the alpha phase was 0.16 h, for the beta phase 1.58 h, and for the gamma phase 83.4 h. The distribution volume at steady state was 1,112 l/m2. The total body clearance was 326.8 ml/m2, showing rapid clearance from the blood. The cumulative urinary excretion in 96 h was 5.17% of the dose. With repeated administration, in one patient without third space, the pharmacokinetics were similar to those of the patients given single administration, but in the other patient with third space, lowered clearance was noted. The pharmacokinetics of mitoxantrone in the Japanese patients were nearly the same as those of European patients, and the blood concentration fitted the three-compartment model, with rapid distribution to the tissues.