Ametantrone is the second anthracene derivative to enter clinical trials. The pharmacokinetic parameters for ametantrone acetate (CI-881) were characterized in six patients concurrently with the phase I clinical trial. Biological samples were assayed by a specific and sensitive high-performance liquid chromatography procedure. Plasma levels of ametantrone declined in a triexponential fashion, with a mean terminal half-life (t 1/2 gamma) of 25 h. The estimated mean total-body plasma clearance was 25.9 +/- 14.7 1 h-1 m-2. The steady-state volume of distribution (Vdss) was large, averaging 568 +/- 630 l/m2. Excretion of unchanged ametantrone in the urine over 48 h averaged 5.7% of the total dose, indicating that there is another major route of elimination.
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