Department of Laboratory Medicine, Section of Psychopharmacology, Centre Hospitalier Sainte-Anne, Paris, France.
Ther Drug Monit. 2010 Dec;32(6):757-61. doi: 10.1097/FTD.0b013e3181fa57fe.
Administration of cyamemazine, an antipsychotic drug with anxiolytic properties, together with other antipsychotic agents is common in patients with schizophrenia. This retrospective study investigated the effects of cyamemazine on the steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone in 47 patients treated with 1 to 12 mg/day of risperidone. Of these 47 patients, 24 were receiving cyamemazine comedication ("cyamemazine" group) and 23 patients were treated with risperidone alone ("control" group). Plasma concentrations were measured using a high-performance liquid chromatographic method with photodiode-array ultraviolet detection. The median plasma concentration of risperidone was significantly higher in the cyamemazine group (31.5 ng/mL) than in the control group (5.0 ng/mL), whereas the 9-hydroxyrisperidone median concentration was significantly lower in the cyamemazine group (16.5 ng/mL versus 39.0 ng/mL in the control group). However, the sum of risperidone plus 9-hydroxyrisperidone (active moiety) plasma concentration was not significantly affected by cyamemazine comedication. A combination with cyamemazine resulted in an inverted metabolic ratio (risperidone/9-hydroxyrisperidone). These findings suggest that cyamemazine inhibits the 9-hydroxylation of risperidone and is probably an inhibitor of cytochrome P450 2D6 as are many other phenothiazine drugs.
氨磺必利是一种具有抗焦虑作用的抗精神病药物，与其他抗精神病药物联合使用在精神分裂症患者中较为常见。本回顾性研究调查了氨磺必利对 47 例接受利培酮 1 至 12mg/天治疗的患者稳态血浆浓度的影响。在这 47 例患者中，24 例接受氨磺必利合并治疗（“氨磺必利”组），23 例患者单独接受利培酮治疗（“对照组”）。采用高效液相色谱法结合光电二极管阵列紫外检测法测定血浆浓度。氨磺必利组利培酮的中位血浆浓度明显高于对照组（31.5ng/mL 比 5.0ng/mL），而氨磺必利组 9-羟基利培酮的中位浓度明显低于对照组（16.5ng/mL 比 39.0ng/mL）。然而，氨磺必利合并治疗并未显著影响利培酮加 9-羟基利培酮（活性部分）的血浆浓度。与氨磺必利合用导致代谢比（利培酮/9-羟基利培酮）倒置。这些发现表明，氨磺必利抑制利培酮的 9-羟化作用，可能是细胞色素 P450 2D6 的抑制剂，就像许多其他吩噻嗪类药物一样。
