Human central nervous system and plasma pharmacology of mitoxantrone

Abstract

Mitoxantrone 5-6 mg/m2 was administered IV to 10 consenting patients prior to surgical resection of an intracerebral tumor. Plasma pharmacokinetic parameters were calculated and concentration of mitoxantrone in intracerebral tumors was determined. Concentrations of mitoxantrone were also determined in autopsy tissues of one of the patients who expired 192 days after receiving the drug. The plasma pharmacokinetics were best described by a 3 compartment model, with a tl/2 gamma of 4.74 +/- 5.53 h. Mitoxantrone concentrations in the intracerebral tumors were potentially cytotoxic and ranged from 4 to 322 ng/g. In all but one case, mitoxantrone concentration was higher in tumor than in concurrent plasma samples. There was no obvious relation between tumor mitoxantrone concentration and peak plasma mitoxantrone concentration or time from mitoxantrone administration to tumor removal. Low grade gliomas and viable tumors tended to have lower mitoxantrone concentrations than did other tumor types and necrotic tumors. In the patient undergoing autopsy, highest mitoxantrone concentrations were found in liver, thyroid and heart.