Clinical studies that focused on treating
schizophrenia showed that
Calculus Bovis Sativus (CBS), a substitute of
Calculus Bovis, when used in combination with
haloperidol could significantly lower the dosage of
haloperidol compared with treatment with
haloperidol alone, whereas efficacy was maintained. The aim of this study was to investigate the synergetic anti-
schizophrenia effects in rats using CBS in combination with
haloperidol. An open field test was conducted to verify the pharmacodynamic effects of a combination treatment of CBS and
haloperidol on MK-801-induced schizophrenic rats. Rat plasma concentrations of intragastric
haloperidol and intravenous
haloperidol were determined after
oral administration of a single dose or 1-week of pretreatment with CBS (50 mg/kg). The pharmacodynamic data showed a significant decrease in locomotor activity and an increase in the percentage of the central distance when
haloperidol was concomitantly administered with CBS compared with
haloperidol administration alone. The AUC0-∞ and Cmax of
haloperidol in the orally coadministered groups were significantly higher compared with the oral treatment with
haloperidol alone. In conclusion, oral coadministration of CBS with
haloperidol resulted in a synergistic effect in rats. The enhanced oral bioavailability of
haloperidol when combined with CBS might be attributed to the interaction between them.