Morselli P L, Bianchetti G, Dugas M
Ther Drug Monit. 1982;4(1):51-8. doi: 10.1097/00007691-198204000-00007.
The available data on haloperidol pharmacokinetics and haloperidol plasma level monitoring in neuropsychiatric patients are reviewed and compared with authors' personal observations. It appears that although haloperidol disposition can be described by linear kinetics in volunteers, this is not the case in patients in whom a 7--10-fold variability in plasma levels is observed for the same dosage together with the possibility of saturation kinetics and/or first pass effect. Anticholinergics may interfere with haloperidol absorption, and significant differences in disposition rate and binding have been observed in children and cirrhotic patients. A clear correlation appears to exist between plasma concentrations and side effects or adverse reactions with threshold levels for extrapyramidal syndromes of 6--9 ng/ml. Threshold levels for therapeutic effects vary with syndromes and age. In Gilles de la Tourette syndrome, active levels are of the order of 1--3 ng/ml, whereas in psychotic syndromes levels of 10--15 ng/ml are requested. In mania, a good therapeutic effect has been observed with plasma levels of 2.5--4.5 ng/ml. In general, children require lower plasma levels for the same therapeutic effects. In chronic unresponsive schizophrenic patients, poor drug bioavailability is not the major factor for the lack of response, and the possibility that these patients constitute a nosological subgroup is suggested. Therapeutic drug monitoring of haloperidol appears justified because (a) no direct relationship exists between daily doses and haloperidol steady-state plasma levels; (b) there is a possibility of saturation kinetics at higher doses; (c) commonly associated drugs or diseases may alter the kinetic profile of the drug; (d) drug disposition is faster in children than in adults; (e) optimal plasma concentration appears to differ in various pathological syndromes and age groups; and (f) side-effects and adverse reactions are clearly related to haloperidol plasma levels.
本文回顾了神经精神疾病患者中氟哌啶醇药代动力学及氟哌啶醇血药浓度监测的现有数据，并与作者的个人观察结果进行了比较。结果显示，尽管氟哌啶醇在志愿者中的处置过程可用线性动力学描述，但在患者中并非如此，相同剂量下患者血浆水平存在7至10倍的变异性，同时存在饱和动力学和/或首过效应的可能性。抗胆碱能药物可能会干扰氟哌啶醇的吸收，且在儿童和肝硬化患者中观察到处置速率和结合存在显著差异。血浆浓度与副作用或不良反应之间似乎存在明显的相关性，锥体外系综合征的阈值水平为6至9纳克/毫升。治疗效果的阈值水平因综合征和年龄而异。在抽动秽语综合征中，有效水平约为1至3纳克/毫升，而在精神病综合征中，所需水平为10至15纳克/毫升。在躁狂症中，血浆水平为2.5至4.5纳克/毫升时观察到良好的治疗效果。一般来说，儿童在相同治疗效果下需要较低的血浆水平。在慢性无反应性精神分裂症患者中，药物生物利用度差并非缺乏反应的主要因素，提示这些患者可能构成一个疾病分类亚组。对氟哌啶醇进行治疗药物监测似乎是合理的，因为：（a）每日剂量与氟哌啶醇稳态血药水平之间不存在直接关系；（b）较高剂量时存在饱和动力学的可能性；（c）常见的相关药物或疾病可能会改变药物的动力学特征；（d）儿童的药物处置比成人快；（e）不同病理综合征和年龄组的最佳血浆浓度似乎不同；（f）副作用和不良反应与氟哌啶醇血药水平明显相关。
