Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia
Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia
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DOI：
10.1007/s00213-007-1029-z
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发表时间：
2008-04-01
影响因子：
3.4
通讯作者：
Suhara, Tetsuya
中科院分区：
文献类型：
--
作者：
Arakawa, Ryosuke;Ito, Hiroshi;Suhara, Tetsuya
帕利培酮ER是一种缓释(ER)剂型的新型抗精神病药物。与所有抗精神病药物一样，谨慎的剂量设置是避免副作用的必要条件。目的本研究采用正电子发射断层扫描(PET)技术，对精神分裂症患者在帕利培酮ER治疗过程中纹状体和纹状体外多巴胺D(2)受体的占有率进行了测量，以比较不同区域的占有率，并估计最佳剂量。其中6人每天服用3 mg帕利培酮ER，4人每天服用9 mg，3人每天服用15 mg。在首次服药后2~6周，于同一天进行两次正电子发射计算机断层扫描，一次是[(11)C]雷克洛必利，一次是[(11)C]FLB457。结果用[(11)C]雷氯普利测得纹状体多巴胺D(2)受体占有率为54.2~85.5%，用[(11)C]FLB457测得颞叶皮质多巴胺D(2)受体占有率为34.5~87.3%。纹状体和颞叶皮质的ED(50)值分别为2.38和2.84 mg/d。纹状体和颞叶皮质多巴胺D(2)受体的占有率无显著差异。结论帕利培酮ER在6~9 mg时，多巴胺D(2)受体的占有率估计在70~80%之间，纹状体和颞叶皮质的多巴胺D(2)受体占有率的大小相似。
Rationale Paliperidone ER is a novel antipsychotic drug in an extended-release (ER) formulation. As with all antipsychotics, careful dose setting is necessary to avoid side effects.Objectives In this study, we measured striatal and extrastriatal dopamine D(2) receptor occupancy during paliperidone ER treatment in patients with schizophrenia using positron emission tomography (PET) to compare regional occupancy and to estimate the optimal dose.Materials and methods Thirteen male patients with schizophrenia participated in this 6-week multiple-dose study. Six of them took 3 mg of paliperidone ER per day, four took 9 mg, and three took 15 mg. Two to 6 weeks after first drug intake, two PET scans, one with [(11)C]raclopride and one with [(11)C]FLB 457, were performed in each patient on the same day. The relationship between the dose or plasma concentration of paliperidone and dopamine D(2) receptor occupancy was calculated.Results The dopamine D(2) receptor occupancies in the striatum measured with [(11)C]raclopride and the temporal cortex measured with [(11)C]FLB 457 were 54.2-85.5% and 34.5-87.3%, respectively. ED(50) values of the striatum and temporal cortex were 2.38 and 2.84 mg/day, respectively. There was no significant difference in dopamine D(2) receptor occupancy between the striatum and the temporal cortex.Conclusions The data from this study suggest that paliperidone ER at 6-9 mg provides an estimated level of dopamine D(2) receptor occupancy between 70-80% and that the magnitude of dopamine D(2) receptor occupancy is similar between the striatum and temporal cortex.