Background:To establish a method for the simultaneous quantification of diazepam (DIA) and its active metabolites, nordazepam (NorD) and oxazepam (OXAZ), and provide a reference range for therapeutic concentrations in patients with alcohol dependence. Methods:Simple and direct protein precipitation was used to extract the biological samples. Subsequent separation was performed on an Agilent XDB-C18 column (50 mm × 4.6 mm, 1.8 μm) with a column temperature maintained at 35 °C and a flow rate of 0.5 mL/min via ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The mobile phase consisted of methanol-water containing 5 mM ammonium formate (75:25, v/v). Detection was conducted using electrospray ionization in multiple reaction monitoring modes: m/z 284.6→193.2 for DIA, m/z 270.5→140.1 for NorD, m/z 286.9→241.1 for OXAZ, m/z 289.6→198.2 for DIA-D5, m/z 275.5→140.0 for NorD-D5, and m/z 291.9→246.1 for OXAZ-D5. The linear response range for DIA, NorD, and OXAZ was 1-1500 ng/mL. Results:The key parameters of the bioanalytical method were validated: the average extraction recovery was 95%-101% (CV <6%); calibration curves exhibited good linearity over the concentration range (R2 ≥0.99 for all analytes); accuracy was within 85%-115%; and intra-day and inter-day precision were satisfactory (CVs <15%). The concentrations of analytes in 26 routine therapeutic drug monitoring (TDM) samples from patients with alcohol dependence were determined. Conclusions:We developed and validated a rapid, simple, and economic UPLC-MS/MS method for the quantification of DIA, NorD, and OXAZ in human serum. The method is well-suited for the determination of serum levels of DIA and its active metabolites in patients with alcohol dependence, and could be further applied to TDM and subsequent studies.

ObjectivesTo characterize the population pharmacokinetics (PPK) of lurasidone in Chinese psychiatric inpatients and to quantify the sources of inter-individual variability, with a specific focus on the impact of valproate (VPA) co-medication and age on drug exposure.MethodsRoutine therapeutic drug monitoring (TDM) data were collected from 156 patients (providing 212 serum concentrations). A PPK model was developed utilizing a nonlinear mixed-effects modeling approach (NONMEM). Model performance was assessed via goodness-of-fit plots, normalized prediction distribution errors (NPDE), and bootstrap analysis. Additionally, model-based simulations were performed to estimate concentration profiles stratified by age and VPA co-medication.ResultsA one-compartment model with first-order absorption and elimination best described the data. The typical estimate for apparent clearance (CL/F) was 339 L·h-1. Age and concomitant VPA were identified as significant covariates. VPA co-administration increased CL/F by 47.7%, leading to significantly reduced systemic exposure. Notably, the majority of observed steady-state concentrations (3–11 ng/mL) fell below the lower limit of the AGNP reference range.ConclusionThe pharmacokinetics of lurasidone in Chinese inpatients were effectively characterized by the established PPK model. Lurasidone exposure in this population is generally lower than the AGNP reference range, particularly in patients receiving VPA. Age and VPA co-medication are critical determinants of CL/F. These findings suggest that TDM interpretation should be adjusted for these factors, and optimal concentration targets for Chinese patients may need to be revisited.

BACKGROUND:The aim of this study was to determine the therapeutic reference range of lurasidone, and to analyze the factors influencing the dose-corrected concentration of lurasidone in Chinese psychiatric patients, thereby providing a basis for the development of individualized dosing of lurasidone. METHODS:A retrospective analysis was conducted for hospitalized patients who had received lurasidone and undergone blood concentration monitoring from May 2022 to September 2023 at the Affiliated Brain Hospital of Guangzhou Medical University. Analyses were based on patient demographic data, treatment regimens, and administered drug concentrations. RESULTS:Data for a total of 123 lurasidone steady-state trough concentrations were collected from 120 hospitalized patients. It was found that 85.56% of lurasidone steady-state trough concentrations were below the lower limit of the lurasidone therapeutic reference range (15 ng·mL -1 ), and that the median steady-state trough concentration was 7.09 ng·mL -1 (IQ1-IQ3 = 4.12-11.82 ng·mL -1 ). Gender, age, and co-medication with valproic acid were found to be significant factors influencing lurasidone steady-state trough concentration/daily dose (C/D) values. C/D values for females were 14% higher than those obtained for males. Among patients who did not receive concomitant administration of valproic acid, the C/D values were 55% higher than those who had received co-administered valproic acid. Furthermore, C/D values obtained for elderly patients (≥60 years) were 140% higher than those recorded for adolescents (<18 years) and 157% higher than those in younger adults (18-60 years). CONCLUSIONS:The findings of this study indicated that the guideline-recommended therapeutic reference range (15-40 ng·mL -1 ) for lurasidone may not be appropriate, at least for the Chinese population. More extensive therapeutic drug monitoring is recommended for elderly female patients and those receiving co-medication with lurasidone and valproic acid.

OBJECTIVES:To analyze the factors affecting the concentrations of the active moiety of risperidone (RIS) and its active metabolite 9-hydroxyrisperidone (9-OH-RIS) in psychiatric outpatients taking immediate-release formulations. METHODS:This is a retrospective study on the therapeutic drug monitoring (TDM) data regarding RIS and 9-OH-RIS in adult psychiatric outpatients. TDM data with simultaneous RIS and 9-OH-RIS monitoring from March 2018 to February 2020 and relevant medical records (including dosage, dosage form, sex, age, diagnosis, combined medication, and comorbid disease) from 399 adult psychiatric outpatients (223 males and 176 females) were included in this study. RESULTS:The daily dose of RIS was 5.56 ± 2.05 mg, the concentration of total active moiety was 42.35 ± 25.46 ng/mL, and the dose-adjusted plasma concentration (C/D) of active moiety was 7.83 ± 3.87 (ng/ml)/(mg/day). Dose, sex, and age were identified as important factors influencing concentrations of RIS and 9-OH-RIS in adult psychiatric outpatients. CONCLUSIONS:Individualized medication adjustments should be made according to the specific conditions of psychiatric outpatients. The findings strongly support the use of TDM to guide dosing decisions in psychiatric outpatients taking RIS.

目的 探讨精神分裂症患者服用帕利哌酮后剂量校正浓度(C/D)的影响因素,为帕利哌酮的临床个体化用药提供参考.方法 选取2019年1月至2021年1月在本院进行过帕利哌酮治疗药物监测的126例精神分裂症患者的138例次血药浓度检测数据.帕利哌酮给药方案为3、6、9或12 mg,qd或bid.收集患者性别、年龄、给药频次、给药剂量、联合用药等资料.用SPSS 25.0软件对数据进行统计分析.用独立样本t检验比较性别、给药频次、联合用药对帕利哌酮剂量校正谷浓度的影响;用One-Way ANOVA方差分析比较年龄对帕利哌酮谷浓度的影响;用多重线性回归分析帕利哌酮C/D的影响因素.结果 性别显著影响帕利哌酮的C/D(P<0.01),女性患者帕利哌酮的C/D(4.86±2.78)ng·mL-1·mg-1·d显著高于男性(3.56±2.36)ng·mL-1·mg-1·d(P<0.01).进行多重线性回归分析,发现性别、联合应用阿立哌唑2个自变量影响帕利哌酮C/D(F=7.03,P<0.001,R2=0.136).结论 本研究结果表明,性别与联合应用阿立哌唑为影响帕利哌酮C/D的2个差异较显著的因素.

目的 建立一种简便快捷的高效液相色谱串联质谱(HPLC-MS/MS)测定人血清中鲁拉西酮浓度的方法.方法 内标选用鲁拉西酮-d8,血清样品处理采用乙腈蛋白沉淀法,色谱柱为Agilent XDB-C18(4.6 mm×50.0 mm,1.8 μm),流动相为甲醇(含5 mmol·L-1甲酸铵和0.1％甲酸)-水-乙腈=66.67 ∶16.67∶16.67,等度洗脱,流速:0.5 mL·min-1,柱温:40℃,进样量:2μL.应用电喷雾离子化,正离子模式下进行多反应监测:对照品鲁拉西酮(m/z 493.10→166.00)和内标鲁拉西酮-d8(m/z 501.10→166.00).结果 鲁拉西酮在1～200 ng·mL-1范围内线性关系良好,准确度在96.57％～99.34％,提取回收率在96.02％～98.39％,日内及日间RSD均小于15％,稳定性考察结果良好.结论 本方法简便快捷,灵敏度高,专属性强,适用于测定临床精神障碍患者中鲁拉西酮的血药浓度监测.

目的 研究服用舒必利患者的剂量校正浓度(C/D)的影响因素,为患者实现舒必利个体化治疗及用药提供依据.方法 收集分析2018年3月至2022年3月在广州医科大学附属脑科医院住院治疗且服用舒必利进行治疗药物浓度监测的患者血药浓度监测数据212份,并收集患者的性别、年龄、体质量指数及合并用药等资料,通过SPSS 25.0软件进行数据统计并对结果进行分析.结果 患者舒必利的给药日剂量为(597.17±17.79)mg·d-1,平均血药浓度为(919.19±41.81)ng·mL-1,其中有43.9％例次超出治疗窗参考范围.性别、年龄、体质量指数对舒必利的C/D产生的影响有统计学意义(均P<0.05).通过多重线性回归分析发现,年龄与体质量指数对舒心利的C/D具有影响(P<0.05).结论 舒必利的血药浓度与剂量相关.临床上使用舒必利时,需根据患者性别、年龄和体质量指数进行给药剂量的调整.患者体质量指数小于18 kg·m-2时,可以考虑适当降低患者服用舒必利的剂量,同时加强治疗药物浓度监测以防药物不良反应的发生.

Background: Alcohol use disorder (AUD) is characterized by chronic excessive alcohol consumption, often alternating with periods of abstinence known as alcohol withdrawal syndrome (AWS). Diazepam is the preferred benzodiazepine for treatment of alcohol withdrawal syndrome under most circumstances, but the specific mechanism underlying the treatment needs further research. Methods: We constructed an animal model of two-bottle choices and chronic intermittent ethanol exposure. LC-MS/MS proteomic analysis based on the label-free and intensity-based quantification approach was used to detect the protein profile of the whole brain. Weighted gene correlated network analysis was applied for scale-free network topology analysis. We established a protein-protein interaction network based on the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software and identified hub proteins by CytoHubba and MCODE plugins of Cytoscape. The online tool Targetscan identified miRNA-mRNA pair interactions. Results: Seven hub proteins (Dlg3, Dlg4, Shank3, Grin2b, Camk2b, Camk2a and Syngap1) were implicated in alcohol withdrawal syndrome or diazepam treatment. In enrichment analysis, glutamatergic synapses were considered the most important pathway related to alcohol use disorder. Decreased glutamatergic synapses were observed in the late stage of withdrawal, as a protective mechanism that attenuated withdrawal-induced excitotoxicity. Diazepam treatment during withdrawal increased glutamatergic synapses, alleviating withdrawal-induced synapse inhibition. Conclusion: Glutamatergic synapses are considered the most important pathway related to alcohol use disorder that may be a potential molecular target for new interventional strategies.

Objective To simultaneously determine venlafaxine（VEN）, O-desmethylvenlafaxine（ODV） and N-desmethylvenlafaxine（NDV） in human serum using LC-MS/MS. Methods Serum samples were prepared by protein precipitation using acetonitrile and separated by a ZORBAX Eclipse XDB-C18 column（4.6 mm×50.0 mm, 1.8 μm） with the mobile phase of acetonitrile-5 mmol·L -1 ammonium formate（20∶80, v/v）. Positive electrospray ionization was employed for mass spectrometric analysis. The specificity, standard curve and lower limit of quantification, precision and recovery, stability, matrix effect of the method were investigated. Results VEN, ODV and NDV were determined in linear ranges of 5-500 ng·mL -1 , 10-1 000 ng·mL -1 and 2-200 ng·mL -1 . The coefficient of variations of IS-normalized matrix effects were no more than 5.76%. The relative and absolute recoveries were 96.87%-99.78% and 99.86%-114.76%, respectively. Intra-day and inter-day precisions were ranged 0.97%-8.55% and 2.20%-6.52%, respectively, while the relative errors were-3.78%-8.50% and-2.73%-5.58%, respectively. VEN, ODV and NDV all exhibited well stability in serum samples after stored at room temperature for 24 h,-20 ℃ for 14 days or freeze-thaw for 3 circles. Conclusion The current method can be applied to therapeutic drug monitoring of VEN,which is able to rapidly feedback the results and guide the clinical rational administration.

IntroductionAbnormal neurotransmission of glutamate and γ-aminobutyric acid (GABA) is a key characteristic of alcohol-related disorders. To track research output, we conducted a bibliometric analysis to explore the current status and trends in this field over the past decades.MethodsStudies related to neurotransmitters and alcohol use disorder published in English from 2005–2021 were retrieved from the Web of Science Core Collection and Scopus databases. The R–bibliometrix package was used for a descriptive analysis of the publications. Citespace, WOSviewer, and R–bibliometrix were used to construct networks of countries/institutions/authors based on co-authorship, co-citation analysis of cited references and co-occurrence as well as burst detection of keywords.ResultsA total of 4,250 unique articles and reviews were included in the final analysis. The annual growth rate of publications was 5.4%. The USA was the most productive country in this field, contributing nearly half of the total documents. The top ten most productive institutions were all located in the USA. The most frequent worldwide collaboration was between the USA and Italy. The most productive and influential institution was the University of California. The author contributing the most productions to this field was Marisa Roberto from the Scripps Research Institute. The top co-cited reference was a review titled “Neurocircuitry of addiction.” The top journal in terms of the number of records and citations was Alcoholism: Clinical and Experimental Research. Comprehensive analyses have been conducted over past decades based on co-cited reference analysis, including modulators, transporters, receptor subtypes, and animal models. In recent years, the research frontiers have been shifting to the identification of risk factors/biomarkers, drug development for alcohol use disorder, and mechanisms related to alcoholic and non-alcoholic fatty liver.ConclusionOur bibliometric analysis shows that glutamate and GABA continue to be of interest in alcohol use disorder. The focus has evolved from mechanisms and medications related to glutamate and GABA in alcohol use disorder, to novel drug development, risk factor/biomarker identification targeting neurotransmitters, and the mechanisms of related diseases.

A high-performance liquid chromatographic method coupled with triple quadrupole mass spectrometry (LC-MS/MS) for the analysis of blonanserin and its active metabolite, N -desethyl blonanserin, in rat plasma has been developed and validated. The biological samples were treated by simple direct protein precipitation before separation on an Agilent Eclipse Plus C 18 column (4.6 × 100 mm, 3.5  μ m) with a column temperature of 35°C at a flow rate of 0.5 mL/min. The mobile phase A is a mixture of methanol and water (75 : 25, v/v, 5 mM ammonium formate), and the mobile phase B is acetonitrile containing 0.1% formic acid. The ratio of mobile phase A to mobile phase B is 15 : 85. Electrospray ionization (ESI) multiple reaction monitoring modes are used for detection, which are m/z 368.10 ⟶ 296.90 (blonanserin), m/z 340.15 ⟶ 297.05( N -desethyl blonanserin), and m/z 348.15⟶ 302.05 ( N -desethyl blonanserin-d 8 ). The linear response range was 0.1–100.0 ng/mL for blonanserin and N -desethyl blonanserin. The lower limit of quantification (LLOQ), calibration curves, carryover, and matrix effects were sufficiently accurate and precise according to the National Medical Products Administration (NMPA) guidelines for bioanalytical method validation. This analytical method was successfully applied in a blonanserin-poloxamer thermosensitive gel pharmacokinetic study in rats.

目的 探讨O-去甲基文拉法辛与文拉法辛血药浓度比值(ratio of 0-desmethylvenlafaxine to venlafaxine concentration,CODV/CVEN)的影响因素.方法 回顾性收集146例次文拉法辛和O-去甲基文拉法辛血药浓度监测的住院患者信息,包括年龄、细胞色素P450 2D6(cytochrome P450 2D6,CYP2D6)基因型、CYP2C19基因型、日剂量、文拉法辛及O-去甲基文拉法辛浓度等信息,用SPSS 16.0软件进行统计分析.结果 ＜60岁和≥60岁患者的CODV/CVEN分别为2.09±1.75和3.15±1.99,差异有统计学意义(P＜0.05).CYP2D6慢代谢者(poor metabolizers,PM)、中间代谢者(intermediate metabolizers,IM)和广泛代谢者(extensive metabolizers,EM)的 CODV/CVEN分别为 1.48±1.43,2.70±1.71 和3.74±2.43,差异均有统计学意义(均P＜0.05).CYP2C19 PM、IM和EM的CODV/CVEN分别为1.41±1.59,2.47±1.76 和 2.59±2.33,PM 的 CODV/CVEN 和IM、EM比较,差异均有统计学意义(均P＜0.05).结论 ≥60岁、CYP2D6 EM的患者可能更适合使用文拉法辛进行治疗.

WHAT IS KNOWN AND OBJECTIVE:Olanzapine is an atypical antipsychotic drug used for mental disorders. There are limited studies providing sufficient pharmacokinetic data, thus the variability of concentrations of olanzapine used in Chinese paediatric patients aged 10 to 17 years remains to be evaluated.METHODS:Therapeutic drug monitoring data were collected from 151 paediatric patients aged 10 to 17 years who received olanzapine. The model was developed with a NONMEM software program. The final model validation and evaluation were assessed by bootstrap, diagnostic scatter plots, and normalized prediction distribution error (NPDE). Regimens of different dosages were simulated to reach the target concentration levels of 20 ng/ml, by using the final model with typical parameters.RESULTS:The one-compartment model was considered the best fit for the data. Typical estimates of the absorption rate constant (Ka), apparent clearance (CL/F), and apparent distribution volume (V/F) in the final model were 0.142 h-1 , 15.4 L/h, and 322 L, respectively. Sex and concomitant valproate (VPA) were included as significant predictors of olanzapine clearance, which was described by the following equation: CL/F = 15.4 × (1 + 0.546 × SEX) × (1 + 0.264 × VPA). Results of Monte-Carlo simulation suggested that male paediatric patients with concomitant VPA were advised to take no less than 15 mg per day of olanzapine orally, and in female paediatric patients with concomitant VPA, a dosing regimen of 10 mg may be sufficient to achieve the therapeutic range of olanzapine.WHAT IS NEW AND CONCLUSION:Our results identified concomitant valproate and sex as significant covariates in olanzapine population pharmacokinetics. Our model may be a useful tool for recommending dosage adjustments for physicians. The pharmacokinetics of olanzapine in patients aged 10 to 17 years was generally similar to that of adults and the elderly.

Objective: To establish a population pharmacokinetic model in Chinese psychiatric patients to characterize escitalopram pharmacokinetic profile to identify factors influencing drug exposure, and through simulation to compare the results with the established therapeutic reference range. Methods: Demographic information, dosing regimen, CYP2C19 genotype, concomitant medications, and liver and kidney function indicators were retrospectively collected for inpatients taking escitalopram with therapeutic drug monitoring from 2018 to 2021. Nonlinear mixed-effects modeling was used to model the pharmacokinetic characteristics of escitalopram. Goodness-of-fit plots, bootstrapping, and normalized prediction distribution errors were used to evaluate the model. Simulation for different dosing regimens was based on the final estimations. Results: The study comprised 106 patients and 337 measurements of serum sample. A structural model with one compartment with first-order absorption and elimination described the data adequately. The population-estimated apparent volume of distribution and apparent clearance were 815 and 16.3 L/h, respectively. Age and CYP2C19 phenotype had a significant effect on the apparent clearance (CL/F). CL/F of escitalopram decreased with increased age, and CL/F of poor metabolizer patients was significantly lower than in extensive and immediate metabolizer patients. The final model-based simulation showed that the daily dose of adolescents with poor metabolizer might be as high as 15 mg or 20 mg and referring to the therapeutic range for adults may result in overdose and a high risk of adverse effects in older patients. Conclusion: A population pharmacokinetics model of escitalopram was successfully created for the Chinese population. Depending on the age of the patients, CYP2C19 genotype and serum drug concentrations throughout treatment are required for adequate individualization of dosing regimens. When developing a regimen for older patients, especially those who are poor metabolizers, vigilance is required.

Introduction: Venlafaxine (VEN) is a widely used dual selective serotonin/noradrenaline reuptake inhibitor indicated for depression and anxiety. It undergoes first-pass metabolism to its active metabolite, O-desmethyl venlafaxine (ODV). The aim of the present study was to develop a joint population pharmacokinetic (PPK) model to characterize their pharmacokinetic characters simultaneously. Methods: Plasma concentrations with demographic and clinical data were derived from a bioequivalence study in 24 healthy subjects and a naturalistic TDM setting containing 127 psychiatric patients. A parent-metabolite PPK modeling was performed with NONMEM software using a non-linear mixed effect modeling approach. Goodness of fit plots and normalized prediction distribution error method were used for model validation. Results and conclusion: Concentrations of VEN and ODV were well described with a one-compartment model incorporating first-pass metabolism. The first-pass metabolism was modeled as a first-order conversion. The morbid state and concomitant amisulpride were identified as two significant covariates affecting the clearance of VEN and ODV, which may account for some of the variations in exposure. This model may contribute to the precision medication in clinical practice and may inspire other drugs with pre-system metabolism.

Paroxetine is one of the most potent selective serotonin reuptake inhibitors (SSRIs) approved for treating depression, panic disorder, and obsessive-compulsive disorder. There is evidence linking genetic polymorphisms and nonlinear metabolism to the Paroxetine’s pharmacokinetic (PK) variability. The purpose of the present study was to develop a population PK (PPK) model of paroxetine in Chinese patients, which was used to define the paroxetine’s PK parameters and quantify the effect of clinical and baseline demographic factors on these PK characteristics. The study included 184 inpatients with psychosis (103 females and 81 males), with a total of 372 serum concentrations of paroxetine for PPK analyses. The total daily dosage ranged from 20 to 75 mg. One compartment model could fit the PKs characterize of paroxetine. Covariate analysis revealed that dose, formulation, and sex had a significant effect on the PK parameters of paroxetine; however, there was no evident genetic influence of CYP2D6 enzymes on paroxetine concentrations in Chinese patients. The study determined that the population’s apparent distribution volume (V/F) and apparent clearance (CL/F), respectively, were 8850 and 21.2 L/h. The CL/F decreased 1-2-fold for each 10 mg dose increase, whereas the different formulations caused a decrease in V/F of 66.6%. Sex was found to affect bioavailability (F), which decreased F by 47.5%. Females had higher F values than males. This PPK model described data from patients with psychosis who received paroxetine immediate-release tablets (IR-T) and/or sustained-release tablets (SR-T). Paroxetine trough concentrations and relative bioavailability were different between formulations and sex. The altered serum concentrations of paroxetine resulting from individual variants and additive effects need to be considered, to optimize the dosage regimen for individual patients.

Background: There is a crucial link between the gut microbiota and the host central nervous system, and the communication between them occurs via a bidirectional pathway termed the “microbiota-gut-brain axis.” The gut microbiome in the modern environment has markedly changed in response to environmental factors. These changes may affect a broad range of host psychiatric disorders, such as depression, by interacting with the host through metabolic, immune, neural, and endocrine pathways. Nevertheless, the general aspects of the links between the gut microbiota and depression have not been systematically investigated through bibliometric analysis. Aim: This study aimed to analyze the current status and developing trends in gut microbiota research in the depression field through bibliometric and visual analysis. Methods: A total of 1,962 publications published between 1999 and 2019 were retrieved from the Web of Science Core Collection. CiteSpace (5.6 R5) was used to perform collaboration network analysis, co-citation analysis, co-occurrence analysis, and citation burst detection. Results: The number of publications has been rapidly growing since 2010. The collaboration network analysis revealed that the USA, University College Cork, and John F. Cryan were the most influential country, institute, and scholar, respectively. The most productive and co-cited journals were Brain Behavior and Immunity and Proceedings of the National Academy of Sciences of the United States of America, respectively. The co-citation analysis of references revealed that the most recent research focus was in the largest theme cluster, “cytokines,” thus reflecting the important research foundation in this field. The co-occurrence analysis of keywords revealed that “fecal microbiota” and “microbiome” have become the top two research hotspots since 2013. The citation burst detection for keywords identified several keywords, including “Parkinson's disease,” “microbiota-gut-brain axis,” “microbiome,” “dysbiosis,” “bipolar disorder,” “impact,” “C reactive protein,” and “immune system,” as new research frontiers, which have currently ongoing bursts. Conclusions: These results provide an instructive perspective on the current research and future directions in the study of the links between the gut microbiota and depression, which may help researchers choose suitable cooperators or journals, and promote their research illustrating the underlying molecular mechanisms of depression, including its etiology, prevention, and treatment.

目的 建立同时测定人血清中氨磺必利和阿立哌唑质量浓度的方法.方法 以乙腈为沉淀剂,通过蛋白沉淀法处理血清样本.色谱柱:Agilent XDB-C18(4.6 mm×50.0 mm,1.8μm),流动相:甲醇-水(含2 mmol·L-1甲酸铵),等度洗脱,柱温:35℃,流速:0.7 mL·min-1,进样量:1μL.电喷雾离子源,正离子化,多反应离子监测.考察该方法的专属性、标准曲线与定量下限、精密度与回收率、基质效应和稳定性.结果 氨磺必利和阿立哌唑均在20～2000 ng·mL-1线性关系良好,定量下限均为20 ng·mL-1,批内和批间精密度RSD在1.43％ ～13.62％,提取回收率为92.95％ ～103.84％,稳定性良好.结论 本方法的样品处理简便,专属性强,稳定性好,适用于单独或联合使用氨磺必利和阿立哌唑药物的患者进行治疗药物监测.

目的 探究舒肝解郁胶囊对精神疾病患者喹硫平血药浓度的影响.方法 回顾性收集服用喹硫平治疗的住院患者的病历资料,记录患者的一般信息、给药方案、肝功能指标以及喹硫平稳态谷浓度等,根据是否联用舒肝解郁胶囊分为试验组(喹硫平联用舒肝解郁胶囊)和对照组(喹硫平).结果 共纳入116例样本信息,其中试验组和对照组的喹硫平血药浓度值分别为(90.76±14.51)和(169.01±15.27)ng·mL-1,剂量校正浓度分别为(0.24±0.04)和(0.47±0.05)ng·mL-1·mg-1·d;试验组和对照组超出治疗窗的比例为70.97％(22例次/31例次)和43.53％(37例次/85例次),差异均有统计学意义(均P<0.01).结论 舒肝解郁胶囊与喹硫平合用能显著降低喹硫平的血药浓度,建议两药合用时适当增加喹硫平的剂量,加强喹硫平血药浓度监测,促进药物临床合理应用.

目的:研究拉莫三嗪在双相情感障碍治疗中剂量校正浓度(C/D)的影响因素,为其个体化用药提供参考.方法:回顾性收集广州医科大学附属脑科医院2019-2020年拉莫三嗪血药浓度监测数据及139例患者统计学资料,考察年龄、性别、合并疾病及合并用药对稳态谷浓度及C/D的影响.结果:患者拉莫三嗪血药浓度均值为(4.64±3.37)μg·mL-1,平均日剂量为(142.35±81.66)mg,患者的C/D均值为(36.06±22.97)μg·mL-1·g-1·d,无合并用药患者与合并丙戊酸用药患者血药浓度分别为(3.2±2.19),(6.42±3.70)μg·mL-1,C/D 分别为(24.76±14.76),(50.31±23.16)μg·mL-1·g-1·d.合并丙戊酸患者组的C/D明显大于无合并用药患者组(P＜0.001).年龄、性别、合并疾病对血药浓度和C/D无显著影响.结论:合并丙戊酸用药可显著增加拉莫三嗪剂量校正后血药浓度,建议合并丙戊酸用药患者可实施拉莫三嗪剂量减半,同时密切监测拉莫三嗪血药浓度,减少不良反应的发生.