Persistence of haloperidol in human brain tissue
Persistence of haloperidol in human brain tissue
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DOI：
10.1176/ajp.156.6.885
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发表时间：
1999-06-01
影响因子：
17.7
通讯作者：
Riederer, P
中科院分区：
文献类型：
--
作者：
Kornhuber, J;Schultz, A;Riederer, P
目的：在停用抗精神病药物后，其抗精神病和抗帕金森作用仍会持续较长时间。尚不清楚抗精神病药物在人体内的长效作用是由于脑组织中药物的持续存在，还是由于药物引起的持久生理变化。本研究的目的是直接检测人脑组织中氟哌啶醇浓度与停药时间的关系。
方法：对11例先前接受氟哌啶醇治疗的患者的尸检大脑的五个区域（颞叶皮质、扣带回、尾状核、齿状核、胼胝体）测量氟哌啶醇浓度。采用高效液相色谱 - 紫外检测法分析氟哌啶醇。通过群体动力学分析估算脑组织中的半衰期。
结果：人脑组织中的氟哌啶醇浓度比用于治疗精神分裂症的最佳血清浓度高10 - 30倍。在单个患者的不同脑区，氟哌啶醇浓度似乎均匀分布。治疗持续时间与平均氟哌啶醇浓度之间没有明显关系。较高剂量的氟哌啶醇似乎与脑组织中较高浓度相关。计算得出从脑组织中的消除半衰期为6.8天。
结论：这些结果可能对临床治疗决策和临床研究方案的设计有影响。在停药后的数周内，不能认为使用过氟哌啶醇的患者没有药物残留效应。
Objective: After discontinuation of neuroleptic drugs, their antipsychotic and antiparkinsonian effects are still present for a prolonged period. It is not known whether the extended effects of neuroleptic drugs in humans are due to the continued presence of drug in brain tissue or to long-lasting drug-induced physiologic changes. The aim of this study was to directly examine haloperidol concentrations in human brain tissue in relation to drug-free time, Method: Haloperidol concentrations were measured in five regions (temporal cortex, cingulate gyrus, caudate nucleus, dentate nucleus, corpus callosum) of the postmortem brains of 11 patients previously treated with haloperidol. Haloperidol was analyzed by means of high-performance liquid chromatography with ultraviolet detection. The half-life in brain tissue was estimated by a population kinetic analysis. Results: Haloperidol concentrations in the human brain tissue were 10-30 times higher than optimal serum concentrations used in the treatment of schizophrenia. Haloperidol concentrations appeared to be homogeneously distributed across different brain areas within a single patient. There was no apparent relation between duration of treatment and mean haloperidol concentration. Higher doses of haloperidol seemed to be related to higher concentrations in brain tissue. The elimination half-life from brain tissue was calculated to be 6.8 days, Conclusions: The results may have implications for clinical treatment decisions and the design of clinical research protocols. Patients exposed to haloperidol cannot be considered to be free of residual effects of the drug for a number of weeks after withdrawal.