Disposition and metabolism of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine in the rat

Abstract

1. After i.v. injection (10mg/kg) to rats, buspirone is rapidly cleared from blood with a t_1/2(β) of 30 min. After the same dose is given orally, the drug is not detectable in blood or brain within the limits of sensitivity of the method.

2. The metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) has a longer t_1/2 than buspirone. It is present to about the same extent in rat plasma and brain after either i.v. or p.o. buspirone.

3. Unlike buspirone, 1-PP accumulates in the brain reaching concentrations between four and five times those in plasma. Its brain AUC is higher than that of buspirone even when buspirone is given i.v.

4. The results suggest that 1-PP may contribute to the pharmacological effect of the parent drug.