The blood concentration and organ distribution of haloperidol at therapeutic and toxic doses in severe fatty liver disease

The aim of this study was to investigate the difference between the pharmacokinetics of haloperidol in normal rats and in rats with fatty liver disease. A therapeutic dosage (0.1 mg/kg) and a toxic dose (15 mg/kg) of haloperidol were administrated to normal 9-week-old male rats or those with severe fatty liver disease, and the blood concentration of haloperidol was determined 15 min, 1, 2, and 3 h following haloperidol administration. The concentration of haloperidol in the organs was determined 1, 2, and 3 h after the haloperidol administration. Additionally, the volume of the portal vein blood flow was measured 3 h after haloperidol administration. When given at the therapeutic dosage, the concentrations of haloperidol in both the blood and organs of the rats with fatty liver disease were significantly higher than those in the normal rats. However, when given at the toxic level, the blood and organ haloperidol concentrations 1 h after administration tended to be lower in the rats with fatty liver disease than those in the normal rats; these lower haloperidol levels returned to be the levels in the normal rats 3 h after the administration of haloperidol. The volume of the portal vein blood flow significantly increased following the toxic haloperidol dose as compared with the volume pre-administration and following the therapeutic haloperidol dose in the normal rats. However, the volume did not change after the toxic or the therapeutic dose of haloperidol compared with pre-administration in rats with severe fatty liver disease, although it was significantly higher than in the normal rats. The pathway for haloperidol metabolism might have been saturated before the administration of haloperidol in rats with fatty liver disease; thus, it is possible that the blood concentration of haloperidol tends to be much higher in individuals with severe fatty liver disease than in those with normal livers in an inverse proportion to the dosage of haloperidol.