Clinical pharmacology of mitoxantrone

A pharmacokinetic study on mitoxantrone was performed within the framework of a phase II clinical trial. Serum concentrations and urinary excretion were measured using a high-performance liquid chromatography method. Four metabolites were separated in urine and three in serum. The two major metabolites cochromatographed with the synthesized monocarboxylic and dicarboxylic acids of mitoxantrone. Within 48 hours, 4.4% of the administered dose was excreted in urine as mitoxantrone, 0.5% as Metabolite 1, and 0.3% as Metabolite 2. The pharmacokinetic parameters are adequately described by a three-compartment model with a terminal half-life of 214.8 hours and a volume of distribution of 2248 L/m2. The total-body clearance was 217 ml/min/m2 and the renal clearance was 15 ml/min/m2. These results suggest that mitoxantrone is sequestered in a deep tissue compartment and only slowly released.