Disposition of timiperone, 4'-fluoro-4-[4-(2-thioxo-1-benzimidazolinyl)piperidino]butyrophenone, a neuroleptic, in the rat on repeated oral dosage

1. The metabolic disposition of [14C]timiperone was studied in male Wistar strain rats receiving an oral dose of 0.5 mg/kg consecutively daily for 21 days. 2. Blood concentrations of 14C indicate that absorption of [14C]timiperone on repeated dosage may be similar to that after a single dose. 3. Tissue levels of 14C after repeated doses were increased to up to double those after a single dose, but the decline of tissue concentrations after the 21st dose was similar to that after a single dose. Thus, no rat tissue show accumulation. 4. Repeated administration did not affect the metabolism of timiperone. 5. Excretion of 14C on the third day of repeated medication was urine, 44.7% and faeces 52.4% of the cumulative dose, and total daily excretions were more than approx. 97% of the cumulative dose in days 3-21 of the repeat dosage schedule.