Pharmacokinetic study of 14C-radiolabelled elliptinium acetate in patients with metastatic breast cancer.

The pharmacokinetics of 14C-labelled elliptinium acetate (Celiptium) was studied in 3 patients with metastatic breast cancer after a 1-h intravenous infusion of the drug at the dose of 100 mg/m2. Total radioactivity measurements were done in plasma, urine and faeces over 120 h. Plasma peak concentration of radioactivity reached during the infusion was 1.6 +/- 0.2 micrograms eq/ml. A comparison with previously published results showed a high ratio of plasma total radioactivity to unchanged drug levels. This could indicate a fast metabolic transformation of the drug. Radioactivity profile in plasma reincreased 8 h after the infusion, strongly suggesting a contribution of biliary radiolabelled metabolites to an enterohepatic cycle. This phenomenon was not observed on the plasma curve of unchanged drug levels, thus indicating that the drug itself and its known conjugates (glucuronide and cysteinyl derivatives) contributed only to a minor extent to the enterohepatic circulation of the drug. More than 70% of radioactivity was recovered in urine and faeces during 120 h for two of the three patients, and fecal excretion appeared to be the major route of elimination of the drug in humans.