BACKGROUND Prior studies have noted great variability in the plasma levels of risperidone(RIS).Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption,metabolism,and other predi...BACKGROUND Prior studies have noted great variability in the plasma levels of risperidone(RIS).Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption,metabolism,and other predictors of metabolic dysregulation;however,these factors are poorly understood and the association between metabolic change and change in psychopathology is uncertain.AIM To ascertain the characteristics of chronic schizophrenic patients treated with RIS,and to assess their relationship with plasma RIS levels.METHODS This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric service.The plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid chromatography.The patients’demographic and clinical characteristics,and psychopathologies were assessed,and the associations between clinical variables and plasma levels of RIS were explored.RESULTS Male patients received higher doses of RIS than female ones,but plasma concentrations of RIS and risperidone+9-hydroxyrisperidone(active moiety)were higher in female patients.Age and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale(PANSS)were significantly positively correlated with plasma concentrations of risperidone+9-hydroxyrisperidone adjusted for weight and dose in all 50 subjects.In male subjects,we found a statistically significant positive correlation between the concentrations of risperidone+9-hydroxyrisperidone in plasma/(dose×kg)and age,mean PANSS negative subscale scores,mean PANSS general psychopathology subscale scores,and mean PANSS total scores.CONCLUSION Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.展开更多
目的:建立利培酮(RIS)血药浓度测定方法,探讨RIS治疗精神分裂症病人的血药浓度与甲状腺功能指标的相关性。方法:血浆样品经乙腈沉淀后,以氯米帕明为内标,采用超高效液相色谱-串联质谱(UPLC-MS/MS)法测定,色谱柱为BEH C 18,流动相为乙腈-...目的:建立利培酮(RIS)血药浓度测定方法,探讨RIS治疗精神分裂症病人的血药浓度与甲状腺功能指标的相关性。方法:血浆样品经乙腈沉淀后,以氯米帕明为内标,采用超高效液相色谱-串联质谱(UPLC-MS/MS)法测定,色谱柱为BEH C 18,流动相为乙腈-水(含5 mmol/L乙酸铵溶液和0.01%氨水),梯度洗脱,流速为0.5 mL/min,柱温为40℃,进样量为2μL,采用多反应监测模式扫描,对UPLC-MS/MS进行方法学考察,将其用于测定116例临床精神分裂症病人血浆中RIS浓度,收集相关病例的住院信息,并探讨RIS血药浓度与甲状腺功能指标的相关性。结果:RIS、9-羟基利培酮(9-OHRIS)在0.4~120.0 ng/mL范围内线性关系良好;日内、日间准确度、提取回收率、基质效应及稳定性均符合要求。病人体内平均稳态血药质量浓度为(49.76±18.07)ng/mL;治疗各时间点病人的稳态血药浓度差异无统计学意义(P>0.05),甲状腺功能指标除促甲状腺激素外(P>0.05),其他4个指标治疗后随着时间的推移呈波动上升趋势(P<0.01);病人的血药浓度与甲状腺功能指标无相关性(P>0.05),但女性病人的RIS血药浓度与四碘甲状腺原氨酸、游离三碘甲状腺素、游离甲状腺素均呈正相关(r=0.480、0.524、0.454,P<0.05)。结论:该方法准确简便、快速灵敏、重现性好,可用于测定精神分裂症病人体内RIS的血药浓度。女性病人体内较高的血药浓度可能会影响甲状腺功能指标,进而影响病人甲状腺功能,需要引起临床的注意。展开更多
基金Supported by Shanghai Civil Administration Bureau,No.8-2-50.
文摘BACKGROUND Prior studies have noted great variability in the plasma levels of risperidone(RIS).Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption,metabolism,and other predictors of metabolic dysregulation;however,these factors are poorly understood and the association between metabolic change and change in psychopathology is uncertain.AIM To ascertain the characteristics of chronic schizophrenic patients treated with RIS,and to assess their relationship with plasma RIS levels.METHODS This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric service.The plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid chromatography.The patients’demographic and clinical characteristics,and psychopathologies were assessed,and the associations between clinical variables and plasma levels of RIS were explored.RESULTS Male patients received higher doses of RIS than female ones,but plasma concentrations of RIS and risperidone+9-hydroxyrisperidone(active moiety)were higher in female patients.Age and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale(PANSS)were significantly positively correlated with plasma concentrations of risperidone+9-hydroxyrisperidone adjusted for weight and dose in all 50 subjects.In male subjects,we found a statistically significant positive correlation between the concentrations of risperidone+9-hydroxyrisperidone in plasma/(dose×kg)and age,mean PANSS negative subscale scores,mean PANSS general psychopathology subscale scores,and mean PANSS total scores.CONCLUSION Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.
