Elucidation of Toxicokinetics/Toxicodinamics(TK/TD) of haloperidol in sever fatty liver rats.

本研究的目的是研究氟哌啶醇在脂肪肝大鼠(FL)和正常肝大鼠(NL)体内的药代动力学差异。给正常和重度脂肪肝大鼠分别给予治疗剂量和过量氟哌啶醇。在治疗剂量下，氟哌啶醇在FL的血液和器官中的浓度均显著高于NL，而在过量剂量时，FL和NL的血液和器官中的氟哌啶醇浓度没有显著差异。NL组大剂量给药后门静脉血流量较给药前和治疗剂量组显著增加，FL组大剂量给药和治疗剂量给药后门静脉血流量较给药前无明显变化，但显著高于NL组。在FL给药前代谢可能已经饱和，因此FL患者的血药浓度可能远高于NL患者，且与氟哌啶醇剂量成反比。

The aim of this study was to investigate the difference in the pharmacokinetics of haloperidol between rats with fatty livers(FL) and those with normal livers(NL). The therapeutic dosage and an overdose of haloperidol were administrated to rats with normal and severe fatty liver. The concentrations in both blood and organs of haloperidol in FL were significantly higher than in NL at the therapeutic dosage, while there was no significant difference between FL and NL in the blood and organ concentrations of haloperidol at the overdose dosage. Additionally, the volume of portal vein blood flow significantly increased after the overdose administration compared with pre-administration and therapeutic dosage in NL, whereas it did not change after the overdose or the therapeutic dosage administration compared with pre-administration in FL, although it was significantly higher than in NL. The metabolism might have been already saturated before the administration of haloperidol in FL, so it is possible that the blood concentration of haloperidol tends to be much higher in the individuals with FL than in those with NL in inverse proportion to the dosage amount of haloperidol.