The clinical pharmacology of mitozantrone

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Abstract
The pharmacological disposition of the anthracenedione mitozantrone has been measured in 11 patients with six different tumour types. Administered at 14 mg/m2 as a 30-min infusion, the drug was assayed by a high-pressure liquid chromatographic technique sensitive to 1 ng mitozantrone/ml plasma. The mean half-lives for mitozantrone in plasma were as follows: α, 9.4 min; β, 1.6 h; γ, 23h. The mean volume of distribution (Vd) was 1565 l. For two patients with impaired liver function the T 1/2 γ and Vd were 63.1 h and 4853 l, respectively. Less than 5% of the administered drug was excreted in urine, but two urinary metabolites were identified. These were not influenced by pre incubation of urine samples with β-glucuronidase or sulphatase, suggesting that neither metabolite is a glucuronide or a sulphate conjugate of mitozantrone. Hepatic metabolism is the major route of elimination of mitozantrone, and caution should be exercised when using this drug for patients with hepatic dysfunction.