奥美拉唑对利培酮血药浓度影响的研究

目的：研究奥美拉唑对利培酮和9-羟利培酮血药浓度的影响.方法：采用自身对照法,对20例精神分裂症伴胃溃疡患者,在利培酮治疗基础上合用奥美拉唑（20 mg·d-1）治疗1周.用高效液相色谱法（HPLC）测定奥美拉唑合用前后利培酮及9-羟利培酮稳态血药浓度进行对比.结果：合用奥美拉唑前与合用1周末后利培酮和9-羟利培酮的血药浓度分别为（29.26±7.84）μg·L-1和（37.17±11.7）μg·L-1,差异有统计学意义（P＜0.05）.结论：奥美拉唑合用利培酮治疗,可使利培酮和9-羟利培酮的血药浓度升高.临床上合用奥美拉唑和利培酮治疗精神分裂症伴胃溃疡患者时,应监控利培酮和9-羟利培酮的血药浓度,调整用药剂量.     

利培酮与9-羟利培酮对精神分裂症患者血药浓度与剂量的关系

目的:探讨口服利培酮的精神分裂症患者利培酮、9-羟利培酮血药浓度、利培酮与9-羟利培酮血药浓度之和及比值与剂量的关系.方法:采用液-质联用法测定利培酮和9-羟利培酮血药浓度;计算利培酮、9-羟利培酮血药浓度及两者之和与剂量的相关系数.结果:利培酮、9-羟利培酮及两者之和与剂量相关系数分别0.766 8,0.980 0和0.979 8.36.6%患者9-羟利培酮血药浓度高于利培酮.结论:9-羟利培酮血药浓度及两者之和比利培酮血药浓度与剂量有更好相关性,9-羟利培酮在精神分裂症治疗中有重要作用.     

利培酮与9-羟利培酮对精神分裂症患者血药浓度与剂量关系的探讨

目的为了进一步探讨利培酮与9-羟利培酮对精神分裂症患者血药浓度与剂量关系,确定在治疗精神分裂症中发挥作用的主要成分。方法对68例口服利培酮的精神分裂患者的血浆用液-质色谱仪进行检测,检测得到的血药浓度与服用剂量的关系用统计学软件处理,分别计算利培酮-剂量,9-羟利培酮-剂量,(利培酮+9-羟利培酮)-剂量三者的相关系数。结果利培酮-剂量的相关系数r1=0.802,9-羟利培酮-剂量的相关系数r2=0.979,(利培酮+9-羟利培酮)-剂量的相关系数r3=0.981。结论 9-羟利培酮在治疗精神分裂症方面发挥着主要作用。     

高效液相色谱法测定血浆中利培酮及9-羟利培酮

目的观察反相高效液相色谱技术测定利培酮及其代谢物9-羟利培酮血浆浓度在临床药物监测中的效果。方法本法选用InertsilODS-3柱为固定相,甲醇：乙腈：水（5：35：60,v/v/v）为流动相,曲唑酮为内标,紫外检测波长280nm。1.0ml待测血浆加内标后,加0.5ml2mol/LNaOH碱化后,加重蒸乙醚4ml提取,乙醚层加1mol/LHCL0.2ml酸化后弃去上层乙醚,氮气吹干,流动相重组后进样分析。结果利培酮及9-羟利培酮最低检测浓度分别为1.56和2.81ng/ml,绝对回收率在80.35%～99.27%之间,日内RSD1.3%～6.7%,日间RSD2.1%～10.9%。结论本法操作简便,灵敏度高,重复性好,适合临床检测。     

多药耐药基因多态性对利培酮及9-羟基利培酮稳态血药浓度的影响

多药耐药基因(MDR1)是跨膜转运体P-糖蛋白(P-gp)的编码基因。胃肠道和血脑屏障等组织中的P-gp可以将包括药物在内的外源性底物排出细胞,影响P-gp底物药物的吸收和分布。MDR1基因多态性会影响P-gp表达和活性,进而影响底物药物的血药浓度和临床疗效,非典型性抗精神药物利培酮及代谢物9-羟基利培酮都是P-gp底物,MDR1基因多态性与这类药物的血药浓度和临床疗效可能相关。     

LC - MS/MS同时测定人血浆中的利培酮和9+羟基利培酮

采用LC - MS/MS法检测人血浆中的利培酮及其活性代谢产物9-羟利培酮.方法采用BEH C18色谱柱(50mm ×2.1 mm,1.7μm),流动相A相为乙腈、B相为0.01 mol·L-1醋酸铵(甲酸调pH3.4),梯度洗脱,流速0.2mL·min-1,柱温45℃,进样量3μL.利培酮、9-羟利培酮及盐酸丁螺环酮...     

利培酮及其活性代谢物血浓度与疗效的相关性研究

目的探讨利培酮及其活性代谢产物9-羟利培酮血浓度与疗效的相关性及护理.方法 24例患者分为干预组(14例)和对照组(10例),所有患者于治疗至第13 d晨,服药前及服药后3 h抽血测血药浓度,并在入组时及治疗后第1、2、3、4周末进行PANSS量表评定.结果 2组患者利培酮的cssmin和cssmax与PANSS总分减分率不相关,但2组患者的利培酮 9-羟利培酮在用苯海拉明抑制前的cssmax与PANSS总分减分率显著正相关.结论利培酮的临床疗效与利培酮 9-羟利培酮的cssmin和cssmax相关.     

反相高效液相色谱法测定人血中利培酮及9—羟利培酮及其临床应用

目的测定人血中利培酮及其活性代谢物9-羟利培酮浓度,探讨其临床意义。方法采用HypersilODS-C18色谱柱(250mm×4.6mmID,粒度5mm),以甲醇水三乙胺(7326.50.5v/v,冰醋酸调pH=8)为流动相,流速1ml.min-1,在UV280nm处测定了16例口服利培酮精神病患者血中利培酮及其活性代谢物9-羟利培酮浓度。结果利培酮及9-羟利培酮在10~100mg.l-1范围内有良好线性关系(r=0.9950及r=0.9935)。方法回收率为98.3%~102.1%,日内及日间变异系数小于6.71%。在每日2~6mg剂量范围内,16例患者利培酮及9-羟利培酮血液浓度分别为10.9~38.8mg.l-1及11.59~49.7mg.l-1。结论测定方法简便、准确、专一性强,可用于临床治疗药物监测及人体内药代动力学研究。在每日2~5mg剂量范围内,利培酮及9-羟利培酮血浓度随服药剂量的增加而升高。     

利培酮血药浓度测定及其临床应用

目的：观察利培酮治疗精神分裂症时的口服剂量,血药浓度及其疗效和不良反应之间的关系。方法：对38例精神分裂症患者,应用利培酮2及4mg,疗程8周,第2,4,8周末采用HPLC测定利培酮及其有效代谢产物9－羟利培酮的血药浓度。治疗前及治疗后第1,2,4,6,8周进行阴阳性症状量表（PANSS）,临床综合印象量表（CCI）,不良反应症状量表（TESS）及锥体外系症状量表（ESRS）评定。结果：利培酮对精神分裂症阴阳性症状均有效,对阴性症状起效时间较阳性症状晚。2及4mg组利培酮及其代谢产物9－羟利培酮血药浓度存在显著差异,但疗效无显著性差异,利培酮及其代谢产物治疗窗可能在30－45ng.mL^-1。结论：采采取逐渐加量的小剂量治疗（2－4mg)方法戏安全又有效,临床上开展利培酮及9－羟利培酮浓度检测对预测疗效,防止不良反应发生是有意义的。     

Relationship between plasma risperidone and 9-hydroxyrisperidone concentrations and clinical response in patients with schizophrenia

RATIONALE: Evaluation of relationships between serum antipsychotic drug concentrations and clinical response may provide valuable information for rational dosage adjustments. For risperidone, this relationship has been little investigated to date. OBJECTIVE: To assess the relationship between plasma concentrations of risperidone and its active 9-hydroxy-metabolite (9-OH-risperidone) and clinical response in schizophrenic patients who experienced an acute exacerbation of the disorder. METHODS: Forty-two patients (30 males, 12 females, age 24-60 years) were given risperidone at dosages ranging from 4 to 9 mg/day for 6 weeks. The design of the study was open and risperidone dosage could be adjusted individually according to clinical response. Steady-state plasma concentrations of risperidone and its 9-hydroxymetabolite were measured after 4 and 6 weeks using a specific HPLC assay. Psychopathological state was assessed at baseline and at weeks 2, 4, and 6 by means of the positive and negative syndrome scale (PANSS), and patients were considered responders if they showed a greater than 20% reduction in total PANSS score at final evaluation compared with baseline. RESULTS: Mean plasma concentrations of risperidone, 9-OH-risperidone, and active moiety (sum of risperidone and 9-OH-risperidone concentrations) did not differ between responders (n = 28) and non-responders (n = 14). No correlation between plasma levels and percent decrease in total PANSS score was found for risperidone (rs = -0.187, NS), 9-OH-risperidone (rs = 0.246, NS), and active moiety (rs = 0.249, NS). Active moiety concentrations in plasma were higher (P < 0.001) in patients developing clinically significant parkinsonian symptoms (n = 7) than in those with minimal (n = 7) or no drug-induced parkinsonism (n = 28). CONCLUSIONS: In chronic schizophrenic patients experiencing an acute exacerbation of the disorder, plasma levels of risperidone and its active metabolite correlate with the occurrence of parkinsonian side effects, whereas no significant correlation appears to exist with the degree of clinical improvement.     

某三甲精神病院利培酮血药浓度监测现状及影响因素分析

目的：通过分析某三甲精神病院利培酮（risperidone,RIS）血药浓度监测（therapeutic drug monitoring,TDM）现状,探索RIS血药浓度影响因素。方法：采用回顾性分析方法,收集2019年7月至2020年7月进行RIS TDM住院患者的检测结果及相关病例资料,分析利培酮、活性代谢物9-羟基利培酮（9-OH-RIS）以及总活性成分（active moiety,AM）血药浓度值的分布情况,探索日剂量、性别、年龄对血药浓度的影响以及体质量和体质指数（body mass index,BMI）与血药浓度的相关性。结果：1 007例患者共行RIS TDM 4 458例次,平均监测次数为4.47次,29.99%例次监测结果不在建议的参考范围（20~60 ng·mL^-1）内,临床实际RIS血药浓度值（C_RIS）、9-OH-RIS血药浓度值（C_9-OH-RIS）以及AM血药浓度值（C_AM）的参考值范围分别为（0.45~39.79）、（8.43~74.87）和（11.74~97.23） ng·mL^-1。C_AM与日剂量具有相关性（ρ=0.536,P<0.01）,C_9-OH-RIS与日剂量具有相关性（ρ=0.570,P<0.01）,C_RIS与日剂量呈较弱的相关性（ρ=0.192,P<0.01）。女性较男性有更高的C_AM与AM浓度剂量比（C/D）值,不同年龄段患者C_AM与C/D值存在差异。体质量与C_AM（ρ=-0.065,P<0.01）和C/D值（ρ=-0.098,P<0.01）呈负相关,与RIS/9-OH-RIS比值（ρ=0.037,P=0.014）呈正相关。BMI与C_AM（ρ=-0.054,P<0.01）和C/D值（ρ=-0.033,P=0.026）呈负相关。结论：临床实际C_AM参考值范围相比于AGNP-TDM专家组推荐的参考范围更宽;日剂量、性别、年龄、体质量和BMI是影响C_AM以及C/D值的重要因素,这些因素或可以为RIS临床个体化用药提供参考。     

利司哌酮所致不良反应国内9年研究概况

汇总国内有关期刊发表的利司哌酮(又名利培酮,商品名维思通)临床研究文献340篇,综合其不良反应发生情况。利司哌酮常见的不良反应有锥外系反应、失眠、便秘、窦性心动过速、头昏、口干、嗜睡、恶心呕吐、体重增加、视物模糊等。     

基于UPLC-MS/MS技术的人血清中利培酮及其代谢产物的治疗药物监测

目的建立一种快速测定人血清中利培酮及其代谢产物9-羟基利培酮浓度的超高效液相色谱串联质谱法(UPLC-MS/MS)。方法以利培酮-d4为内标,以Waters Acquity UPLC BEH C18(2.1×50 mm,1.7μm)为色谱柱,柱温:50℃,0.1%甲酸水溶液(A)~0.1%甲酸甲醇(B)为流动相,快速进行治疗药物监测。结果在1~100 ng/ml,利培酮和9-羟基利培酮的线性良好(r>0.999),低、中、高质控的日内和日间精密度的RSD均小于6.0%,基质效应在92.4%~106.7%,RSD小于6.5%。结论本方法操作简单,灵敏度高、准确度好,可在4 min中完成一次标本检测,通量高,可满足临床对利培酮和9-羟基利培酮检测的需求。     

利培酮药物浓度监测及正常范围参考值的初步建立

目的 通过大样本的治疗药物浓度监测,建立利培酮的正常范围参考值,探索其部分相关因素.方法 收集利培酮治疗2周以上的住院病例的高效液相色谱技术(HPLC)-电化学方法测定所得的利培酮和其代谢产物9-羟利培酮(9-OH-RSP)浓度数据,共3670例,采用SPSS17.0软件分析.结果 18～60岁组女性9-OH-RSP...     

Prolactin elevation of the antipsychotic risperidone is predominantly related to its 9-hydroxy metabolite

OBJECTIVE: Treatment with the antipsychotic risperidone is frequently associated with hyperprolactinemia. The aim of this study was to evaluate the role of the main compound risperidone and its active 9-hydroxy metabolite on elevating prolactin levels. METHODS: Twenty patients with psychotic disorders, on therapy with risperidone, were studied. All patients had been receiving risperidone for at least 2.5 months, and the median daily dose of risperidone was 3 mg (range 1-10). Morning serum samples for prolactin were analyzed and investigated in relation to the serum concentrations of risperidone and 9-hydroxyrisperidone. RESULTS: Elevated prolactin levels were found in 17 (85%) of the patients. Levels of prolactin were positively correlated to the 9-hydroxyrisperidone serum concentration (r(s) = 0.48, p = 0.03) and to the daily dose of risperidone (r(s) = 0.51, p = 0.03), but did not correlate to the risperidone serum concentration. CONCLUSION: The present results suggest that 9-hydroxyrisperidone and not risperidone is the main contributor to the increased serum levels of prolactin observed in many risperidone-treated patients.     

利培酮治疗汉族精神分裂症患者时血药浓度与临床疗效的关系

目的 探讨利培酮治疗汉族精神分裂症患者时利培酮和代谢产物9-羟利培酮血药浓度与临床作用的关系.方法 采用开放、自身对照研究.入组精神分裂症患者363例,男性195例,女性168例.用临床总体印象量表(CGI-S、CGI-I)评价疾病严重程度和疗效.结果 [1]利培酮血药浓度为(9.70±10.24)μg·L-1,9-羟利培酮浓度为(31.07±18.02)μg·L-1,总浓度为(40.77±23.22)μg·L-1.女性患者血药浓度显著高于男性.[2]利培酮、9-羟利培酮及总血药浓度与CGI-I之间均未发现显著性的相关.治疗有效组(191例)与无效组(172例)相比,2组在剂量、药物血药浓度等方面的差异均无统计学意义.[3]锥体外系反应(EPS)组的平均病程及平均住院次数显著少于无EPS组.结论 利培酮治疗汉族精神分裂症患者时,女性患者浓度显著高于男性,与疗效之间未见显著相关性.