Therapeutic Drug Monitoring of 1 106 Cases of Vancomycin Therapy and Analysis of Risk Factors / 医药导报

Objective To analyze the achievement of target vancomycin concentration and the risk factors affecting the concentration to reach the target,providing a reference for the rational use of vancomycin and the implementation of therapeutic drug monitoring(TDM).Methods Patients who were hospitalized and received vancomycin TDM from January 2016 to June 2019 at Zhongshan Hospital,Fudan University were selected.Clinical data,vancomycin blood concentrations,and occurrences of acute kidney injury(AKI)during the hospitalization were collected.Factors affecting the attainment of target vancomycin concentrations were analyzed using logistic regression and grouped according to whether the target concentrations were attained.The correlation between drug concentration and the occurrence of AKI was analyzed.Results A total of 1 106 patients were included,with 70.7％being males and a median age of 60.0(IQR=20)years.Surgical departments accounted for 76.4％of the distribution.The median duration of vancomycin therapy was 10.8 d(IQR=9.0).A total of 21.6％of patients had their first concentration monitored before administration of doses 4 and 5.The drug concentration monitoring results of 46.8％(518/1 106)of patients were in the range between 10-20 μg·mL-1,reaching the target concentration range.The incidence of vancomycin-associated AKI was 25.9％.The incidence of AKI varied among patients with different vancomycin concentrations:when the concentrations are＜10,10-＜15,15-20,and＞20 μg·mL-1,the AKI rates are 15.8％,20.5％,25.8％,and 39.4％,respectively.Multivariate logistic regression analysis showed that target concentrations were more likely to be reached with a dosing course of＞7-14 d(OR=1.688,P=0.001)and＞14 d(OR=1.744,P=0.002)than with a dosing course of ≤7 d.Patients receiving conventional daily doses were more likely to achieve target concentrations than those receiving the non-conventional daily dose(OR=1.540,P=0.003).Conclusion The current status of vancomycin TDM in China still suffers from deficiencies,such as delayed timing of monitoring and low rate of target concentration attainment.Higher vancomycin concentrations are significantly associated with AKI,and the factors affecting the vancomycin concentration to reach the target mainly include treatment duration and the complexity of the dosing regimen.

Detection and In-house Quality Control Assessment for Cyclosporin A and Tacrolimus by High Performance Liquid Chromatography-tandem Mass Spectormetry Method / 医药导报

Objective To establish a quality control method for monitoring the blood concentrations of cyclosporin A and tacrolimus by HPLC-MS/MS,and to evaluate the quality control samples using the Westgard multi-rule theory.Methods HPLC-MS/MS was used to determine the concentration of cyclosporin A and tacrolimus in human whole blood.The quality control samples of low,medium and high concentration levels in the therapeutic drug monitoring process were statistically analyzed,Levery-Jennings and Z-score quality control charts were drawn,and the Westgard multi-rule theory was applied for in-house quality control evaluation.Results The established method was fully validated with linear ranges of 10.40-1 040.00 ng·mL-1 and 0.50-49.50 ng·mL-1,the quantification limits were 10.40 and 0.50 ng·mL-1,respectively.The extraction recoveries were 108.61％-113.24％and 101.99％-109.37％,respectively.The matrix factors normalized by internal standard were 106.68％-111.27％and 95.70％-97.81％for cyclosporin A and tacrolimus,respectively.The intra-day and inter-day accuracy and precision were less than 15.0％.Other parameters were also validated and met the acceptance criteria.Levery-Jennings and Z-score quality control charts showed that there were 4 warnings(violation of the 12s rule)in the results of the 26 groups of quality control samples in the third quarter of 2022,and no phenomenon was observed to be out of control.Conclusion The established in-house quality control system for therapeutic drug monitoring of cyclosporin A and tacrolimus can effectively ensure the accuracy of blood drug concentration detection.

Simultaneous Determination of Blood Concentrations of Five Antiretrovirals in Human Plasma by Ultra High Performance Liquid Chromatography-tandem Mass Spectormetry Method / 医药导报

Objective To develop an ultra-performance liquid chromatography-mass spectrometry(UPLC-MS/MS)method for the simultaneous quantification of dolutegravir,raltegravir,efavirenz,lamivudine and tenofovir in human plasma and to apply it to the therapeutic monitoring.Methods Dolutegravir-D5,raltegravir-D4,efavirenz-D5,lamivudine-13 C-15 N2 and tenofovir-D7 were used as internal standard,respectively.All samples were extracted using the protein precipitation method with acetonitrile and then diluted for analysis.Chromatographic separation was performed on Shim-pack XR-ODS Ⅲ(2.0 mmx50 mm,1.6 μm)column.Mobile phases A and B consisted of 0.1％formic acid in water and acetonitrile respectively.A programmed mobile phase gradient was used at a flow rate of 0.3 mL·min-1 and column temperature of 40 ℃.The tandem mass spectrometer was equipped with an electrospray ionization(ESI)source operating in multiple reaction monitoring(MRM)modes.After methodological validation,it can be used for therapeutic drug monitoring in HIV patients.Results There was good linearity in the validated concentration ranges of 62.5-3 000 ng·mL-1 for dolutegravir,10-500 ng·mL-1 for raltegravir,125-6 000 ng·mL-1for efavirenz,10-500 ng·mL-1 for lamivudine and 10-500 ng·mL-1 for tenofovir with the linear correlation coeffificients of determination(R2)of all higher than 0.998.The accuracy of both intra-day and inter-day studies ranged from 94.0％-109.3％,and the relative standard deviations were less than 7％.The IS-normalized matrix factor and extraction recoveries of all analytes were 95.7％-106.0％and 98.7％-104.5％at all concentrations.All analytes were stable in plasma at a certain storage environment.The trough blood concentrations of dolutegravir,efavirenz,lamivudine and tenofovir were 107.7-2 366.0,740.0-3 410.0,38.5-1 229.3,31.6-224.4ng·mL-1 in HIV patients,respectively.Conclusion The method is highly aceurate,easy to perform,low-cost,and suitable for therapeutic drug monitoring of dolutegravir,raltegravir,efavirenz,lamivudine and tenofovir in HIV patients.

Evaluation of the predictive ability of individualized drug administration adjuvant decision-making system JPKD for tacrolimus blood concentration in kidney transplant recipients / 器官移植

Objective To evaluate the predictive ability and influencing factors of individualized drug administration adjuvant decision-making system Java PK® for Desktop (JPKD) for tacrolimus blood concentration in kidney transplant recipients. Methods The monitoring data of tacrolimus blood concentration from 149 recipients early after kidney transplantation were collected. The trough blood concentration of tacrolimus was predicted by JPKD. The absolute weighted deviation and relative prediction deviation between the actual and predicted concentration were calculated. The influencing factors of the absolute weighted deviation were analyzed by univariate and multivariate logistic regression analyses, and the predictive values of these influencing factors on the accuracy of software prediction were assessed by delineating the receiver operating characteristic (ROC) curve. Results Two hundred and sixty-six samples of tacrolimus blood concentration data were collected from 149 patients. The measured blood concentration of tacrolimus was (6.5±3.0) ng/mL (1.1-16.6 ng/mL), and the predicted value calculated by JPKD was (5.6±2.5) ng/mL (1.4-14.4 ng/mL). The absolute weighted deviation of the calculated data was 28.38%, and the relative prediction deviation was −13.55%. Univariate analysis showed that gender, albumin, changes in hematocrit, cytochrome P450 (CYP)3A5*3 genotype and C3435T genotype were associated with the inaccurate prediction results. Multivariate logistic regression analysis found that CYP3A5*3 genotype of AA and the changes in hematocrit were the independent risk factors affecting the accuracy of tacrolimus blood concentration predicted by JPKD. ROC curve analysis showed that when the changes in hematocrit exceeded 2.25%, the risk of inaccurate software prediction was increased. Conclusions JPKD possesses certain accuracy in predicting the blood concentration of tacrolimus in kidney transplant recipients, which may improve the qualified rate of tacrolimus blood concentration. Nevertheless, CYP3A5*3 genotype and the changes of hematocrit may affect the accuracy of predictions.

Advances in therapeutic drug monitoring methods based on liquid chromatography-tandem mass spectrometry / 中华检验医学杂志

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology has the characteristics of high specificity and high throughput, making it rapidly applied and developed in the field of clinical testing. Its application in the monitoring of therapeutic drugs can effectively improve the quantitative accuracy and sensitivity, and formulate a personalized and optimal dosing plan for patients. However, this technology still faces some challenges, and automation, quality control, and quantitative traceability will be the future development direction.

Application progress on in vivo drug analysis technique in clinical pharmacy / 药学实践与服务

Objective To explore the progress on the application of in vivo drug analysis techniques in clinical pharmacy work. Methods Relevant literature was reviewed to provide an overview of the characteristics of clinical samples, common in vivo drug analysis methods used in the clinic, the application and existing problems of in vivo drug analysis in clinical pharmacy. Results and Conclusion In recent years, with the increasing demand for individualized and precise treatment in clinical practice and the continuous development of analytical techniques, in vivo drug analysis techniques have been widely used in clinical pharmacy work, which have become one of the important auxiliary techniques to promote rational clinical drug use, improve individualized treatment and reduce the occurrence of adverse reactions. However, in the actual application, there were still problems such as the invasive blood sampling that hinders sampling, the weak ability to interpret drug monitoring results and clinical testing methods that still need to be improved. These problems should be taken seriously and continuously improved and solved in the subsequent research and application.

Quality evaluation of Chinese and global guidelines/consensus for TDM of anti-TNF-α agents in patients with inflammatory bowel disease / 中国药房

OBJECTIVE To evaluate the quality of guidelines/consensus on therapeutic drug monitoring （TDM） of anti-tumor necrosis factor-α （TNF-α） in patients with inflammatory bowel disease （IBD） in China and globally. METHODS PubMed， Embase， CNKI， Wanfang data， VIP， and release websites of guidelines/consensus in China and globally were searched to collect guidelines/expert consensus on TDM with anti-TNF-α for IBD patients. The search period was from database establishment to June 2023. After two investigators independently screened the literature and extracted the data， the methodological quality of the included guidelines/consensuses was evaluated using the Appraisal of Guidelines for Research and Evaluation Ⅱ. The main recommendations of the included guidelines/consensuses were summarized. RESULTS A total of 9 articles were included， 3 were guidelines and 6 were expert consensus. The standardized percentages of the 9 guidelines/consensus in the 6 dimensions （scope and aims， participants， rigor of formulation， clarity of expression， application， and editorial independence） were 90.43%， 41.98%， 52.55%， 85.49%， 19.00%， and 76.85%， respectively. Eight guidelines/consensus had a recommendation of grade B and one consensus of grade C. The main recommendations involve TDM application scenarios， threshold ranges， strategy adjustments， detection methods， and interpretation of results. Most guidelines/consensus recommend passive TDM for non-responders. It is recommended to set the TDM concentration range according to the expected treatment results and make strategy adjustments in combination with the disease condition and TDM results. Additionally， the same test method is recommended for the same patient. Some guidelines/consensus hold that no differences were noted in the interpretation of results between biosimilar and original drug. CONCLUSIONS The overall quality of the included guidelines/consensus was fair， with relatively consistent recommendation. Clinicians need to understand the characteristics and limitations of TDM with this class of drugs， and interpret and apply results of TDM in combination with specific clinical treatment goals.

Investigation of patients’preferences regarding therapeutic drug monitoring of mycophenolic acid in solid organ transplantation / 中国药房

OBJECTIVE To investigate the preferences of patients who underwent solid organ transplantation regarding therapeutic drug monitoring （TDM） of mycophenolic acid （MPA） and explore the factors influencing patients’ decision-making process， so as to provide support for the development of individualized medication guidelines for MPA and improvement of clinical decision-making. METHODS The cross-sectional study was used to design the questionnaire on the patients’ preferences to accept MPA TDM， and involved patients who underwent solid organ transplantation and received MPA treatment at two tertiary hospitals in Beijing from April 14， 2022， to June 27， 2022. The Likert 5-level scoring method was used to score the patients’ preferences to accept MPA TDM， the influencing factors and their correlation of the patients’ preferences to accept MPA TDM were analyzed by Pearson correlation analysis and binary Logistic regression analysis， and the nonparametric test and chi-square test were used to rank and analyze the consistency of the factors affecting patients’ preference decision. RESULTS A total of 140 questionnaires were collected， and the effective recovery rate was 77.35%. The average preference score of 140 patients to receive MPA TDM was （4.01±0.65）， and the overall preference value was high. There were 116 （82.86%） patients agreed or strongly agreed with MPA TDM. Significant differences were observed in preference scores between patients who had previously undergone MPA TDM and those who had never undergone it （[ 4.30±0.53） scores vs. （3.80±0.65） scores， P＜0.001]. Additionally， patients’ preference scores were significantly influenced by their understanding level and attention level （P＜0.001）. The ranking of factors contributing to decision-making exhibited consistency （P＜0.001）. The factors were ranked in descending order of clinical efficacy， safety， comfortability， economy and time cost. CONCLUSIONS The patients who underwent solid organ transplantation hold high preferences towards MPA TDM. The primary factors influencing their decisions are their prior experience， understanding level， and attention level.

Research progress in therapy drug monitoring of levetiracetam / 中国药房

Levetiracetam （LEV） is the second generation of broad-spectrum anti-epileptic drug. LEV has the advantages of rapid absorption， short half-life， precise efficacy， good tolerance and few drug interactions. In order to improve the clinical efficacy of LEV， and reduce the occurrence of adverse reactions， children， pregnant women， the elderly， and patients with renal insufficiency should receive therapeutic drug monitoring （TDM）. Clinically， the samples are usually plasma or serum， and the TDM methods are mostly immunoassay or chromatography. There is currently no consensus on the effective concentration range of LEV， and the correlation between plasma concentration and adverse reactions is also unclear. The main factors affecting LEV plasma concentration include age， pregnancy， and patient compliance. How to interpret TDM results and adjust dosage based on the results will be the focus of future work.

Standardization and validation of a high-efficiency liquid chromatography with a diode-array detector (HPLC-DAD) for voriconazole blood level determination / Estandarización y validación de un método de cromatografía líquida de alta eficiencia con detector de arreglo de diodos (HPLC-DAD) para la determinación de niveles sanguíneos de voriconazol

Abstract Introduction. A specialized service for antifungal blood level determination is not available in Colombia. This service is essential for the proper follow-up of antifungal therapies. Objective. To standardize and validate a simple, sensitive, and specific protocol based on high-performance liquid chromatography with a diode array detector for voriconazole blood level quantification. Materials and methods. We used an Agilent HPLC™ series-1200 equipment with a UV- diode array detector with an analytical column Eclipse XDB-C18 and pre-column Eclipse- XDB-C18 (Agilent). We used voriconazole as the primary control and posaconazole as an internal control. We performed the validation following the Food and Drug Administration (FDA) recommendations. Results. The best chromatographic conditions were: Column temperature of 25°C, UV variable wavelength detection at 256 nm for voriconazole and 261 nm for posaconazole (internal standard); 50 μl of injection volume, 0,8 ml/min volume flow, 10 minutes of run time, and mobile phase of acetonitrile:water (60:40). Finally, retention times were 3.13 for voriconazole and 5.16 minutes for posaconazole. Quantification range varied from 0.125 μg/ml to 16 μg/ml. Conclusion. The selectivity and chromatographic purity of the obtained signal, the detection limits, and the standardized quantification make this method an excellent tool for the therapeutic monitoring of patients treated with voriconazole.

Resumen Introducción. Hasta la fecha, Colombia no cuenta con un servicio especializado de medición de niveles séricos de antifúngicos, procedimiento esencial para el adecuado seguimiento del tratamiento de infecciones fúngicas invasoras. Objetivo. Estandarizar y validar un protocolo -simple, sensible y específico- basado en la aplicación de cromatografía líquida de alta eficiencia acoplada con un detector de arreglo de diodos para la cuantificación de los niveles séricos de voriconazol. Materiales y métodos. Se usó un equipo HPLC-AgilentTM, serie-1200, con un detector UVDAD, una columna analítica Eclipse-XDB-C18 y una pre-columna Eclipse-XDB-C18, ambas de la marca Agilent. Como control primario se utilizó voriconazol y como control interno, posaconazol. La validación se hizo cumpliendo todos los criterios de aceptación recomendados por la Food and Drug Administration (FDA). Resultados. Las mejores condiciones cromatográficas se obtuvieron con los siguientes parámetros: temperatura de la columna de 25 °C, detección UV-VWD de 261 nm, volumen de inyección de 50 μl, flujo de 0,8 ml/minuto y un tiempo de corrido de 10 minutos. La fase móvil usada fue acetonitrilo:agua (60:40) y los tiempos finales de retención fueron de 3,13 para voriconazol y de 5,16 minutos para posaconazol. El rango de cuantificación fue desde 0,125 μg/ml hasta 16 μg/ml. Conclusiones. La selectividad y la pureza de la señal cromatográfica, así como los límites de detección y cuantificación estandarizados hacen de esta metodología una excelente herramienta para el seguimiento terapéutico de pacientes tratados con voriconazol o en profilaxis con este fármaco.

Side effects of chronic systemic glucocorticoid therapy: what dermatologists should know

Abstract In dermatologists' clinical practice, the use of systemic glucocorticoids is recurrent for the management of different comorbidities that require chronic immunosuppression. The prescription of this medication requires caution and basic clinical knowledge due to the several adverse effects inherent to the treatment. However, different doubts may arise or inappropriate conduct may be adopted due to the lack of objective and specific guidelines for the screening, prophylaxis and management of complications from chronic corticosteroid therapy. Considering this problem, the authors carried out a narrative review of the literature to gather up-to-date data on adverse effects secondary to the chronic use of systemic glucocorticoids. The broad approach to this topic made it possible to review the pathophysiology and risk factors for these complications, as well as to develop updated orientation that can be used as a learning tool and quick reference for dermatologists during their clinical practice with glucocorticoids.

Evaluation of proactive therapeutic drug monitoring application in infliximab users in ulcerative colitis

Objective: To evaluate the application of proactive pro-drug therapy (TDM) at week six in users of infliximab therapy in ulcerative colitis patients and to analyze the need for further disease optimization. Method: This is a retrospective analysis that will be carried out simultaneously at the Hospital de Clínicas de Passo Fundo and at the Endoclin Diagnostic Center in the city of Passo Fundo, with secondary data collection between January 2020 and May 2022. The sample included patients from both sexes, regardless of age, who are being followed up in the services mentioned above, by signing the informed Free and Clarified Consent Term. Results: 63.2% of patients required optimization of their treatment based on the serum level assessment at week six. Conclusion: Proactive TDM performed at week six benefits patients in order to complete indications for treatment to avoid lack of drug response and complications from the disease. (AU)

Therapeutic drug monitoring in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a problem that directly affects the quality of life of patients suffering from this condition. Monitoring the serum level of infliximab (IFX) (TDM) is an important tool for guiding therapeutic decisions in IBD patients. The purpose of this study was to determine the significance of quantitatively measuring the serum level of IFX (TDM) and antibody to IFX (ATI). Methods and materials: Prospective observational study involving 40 IBD patients on IFX therapy, including 14 Proactive (week 06 of the induction phase) and 26 Reactive (maintenance phase). Immediately prior to the infusion, blood samples were drawn and measured using a Bulhlmann rapid test instrument. Serum concentrations of IFX were categorized as supratherapeutic (>7.0 micrograms/ml), therapeutic (between 3.0 and 7.0 micrograms/ml), and subtherapeutic (3.0 micrograms/ml). When the serum concentration of IFX was 3 mcg/ml (subtherapeutic), the ATI was measured. 25 patients with CD and 15 patients with UC were evaluated. Only three of the twenty patients with subtherapeutic serum levels had a positive ATI, and both were reactive; two had CD and one had UC. There was a statistically significant difference between reactive and proactive patients with respect to levels of CRP (p = 0.042), with proactive DNS patients suffering greater alterations in CRP and albumin. (AU)

Application of machine learning in the therapeutic drug monitoring and individual drug therapy / 中国药房

Machine learning has been applied in the medical field due to its powerful data analysis and exploration capabilities. In recent years， more and more studies have applied it to therapeutic drug monitoring and individual drug therapy of immunosuppressants， anti-infective drugs， antiepileptic drugs， etc. Compared with the traditional population pharmacokinetic modeling methods， the constructed models based on machine learning can predict blood drug concentration and drug dose more accurately， improve the level of clinical precision drug use and reduce the occurrence of adverse drug reactions. Based on this， this article reviews the application of machine learning in therapeutic drug monitoring and individual drug therapy， with a view to providing theoretical basis and technical support for clinical precise drug use.

Chinese consensus guidelines for therapeutic drug monitoring of polymyxin B, endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.

Effects of plateau hypoxia on pharmacokinetic parameters and cerebral-blood distribution of levetiracetam in rats / 中南大学学报(医学版)

Objective:Plateau hypoxia exposure causes changes in pharmacokinetic parameters and cerebral-blood distribution of drugs,including many substrates of P-glycoprotein(P-gp).Levetiracetam,a kind of antiepileptic drugs,is a substrate of P-gp.Whether plateau hypoxia exposure changes its pharmacokinetic characteristics and cerebral-blood distribution remains unclear.This study aims to investigate the effects of plateau hypoxia on the pharmacokinetics and cerebra-blood distribution of levetiracetam. Methods:Wistar rats were divided into a low-altitude control group,a high-altitude group,a solvent group,and a P-gp induction group.After 24 h of exposure at altitude of 4 010 m,rats in the high-altitude group were given levetiracetam orally or intravenously.The plasma was respectively collected at 0.083,0.25,0.5,0.83,1.25,2,4,6,8,10,12,and 24 h after oral administration of the drug,while both plasma and brain were respectively collected at 5,45,60,120 and 240 min after intravenous injection.After 3 days administration of dexamethasone,plasma and brain of rats in the P-gp induction group were collected at 120 min after intravenously giving levetiracetam.Plasma and brain concentrations of the drug were determined by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).The expression of P-gp in blood-brain barrier was detected by Western blotting. Results:Compared with the low-altitude control group,the area under the curve(AUC)and mean residence time(MRT)of levetiracetam were respectively decreased by 14.69%(P<0.01)and 15.42%(P<0.01),while the clearance(CL)was increased by 16.67%(P<0.01)in the high-altitude group.The ratio of brain/blood plasma drug concentration was decreased by 22.82%(P<0.05),12.42%(P<0.05),17.40%(P<0.01),and 13.22%(P<0.01)at 5,45,120,and 240 min after injection,respectively.The expression of P-gp on the blood-brain barrier was increased by 86.3%(P<0.05).Compared with the solvent control group,the expression of P-gp on the blood-brain barrier in the P-gp induction group was increased by 56.3%(P<0.05),the ratio of brain/blood plasma drug concentration was decreased by 19.3%(P<0.05). Conclusion:After acute plateau hypoxia exposure,the pharmacokinetic of levetiracetam in rats are altered,and the cerebral-blood distribution of the drug in rats is decreased,which may be related to the up-regulation of P-gp expression on the blood-brain barrier.

Effect of Proactive and Reactive Therapeutic Drug Monitoring of Infliximab on Prognosis of Patients With Inflammatory Bowel Disease / 胃肠病学

Background:Therapeutic drug monitoring(TDM)has emerged as the important method for managing loss of response to infliximab.The effect of reactive and proactive TDM on clinical outcomes in inflammatory bowel disease(IBD)is uncertain.Aims:To evaluate the effect of proactive and reactive TDM of infliximab on the prognosis of patients with IBD.Methods:Clinical data of 99 IBD patients treated with IFX from January 2017 to October 2021 at the First Affiliated Hospital of Air Force Military Medical University were retrospectively analyzed,including 34 patients with proactive TDM and 65 patients with reactive TDM.The rate of treatment failure,IBD-related surgery or hospitalization were compared between the two groups.Logistic regression analysis was used to determine the independent risk factors of treatment failure.Results:The median follow-up of the patients was 21(13,32)months.The rate of treatment failure,IBD-related hospitalization rate of proactive TDM group were significantly lower than those of reactive TDM group(P<0.05),however,no significant difference in IBD-related surgery rate was found between two groups(P=0.081).Univariate analysis showed that ileocolonic resection before TDM,antibodies to infliximab(ATI)and reactive TDM might be correlated with treatment failure(P<0.05).Logistic regression analysis showed that reactive TDM(OR=5.829,95%CI:1.070-31.754,P=0.042)was the risk factor of treatment failure,and ileocolonic resection before TDM(OR=0.119,95%CI:0.019-0.736,P=0.022)was the protective factor of treatment failure.Conclusions:Compared with reactive TDM group,proactive TDM can significantly decrease the rate of treatment failure and IBD-related hospitalization rate.Reactive TDM is the risk factor of treatment failure,and ileocolonic resection before TDM is the protective factor of treatment failure.

In vivo solid phase microextraction for therapeutic monitoring and pharmacometabolomic fingerprinting of lung during in vivo lung perfusion of FOLFOX / 药物分析学报

In vivo lung perfusion(IVLP)is a novel isolated lung technique developed to enable the local,in situ administration of high-dose chemotherapy to treat metastatic lung cancer.Combination therapy using folinic acid(FOL),5-fluorouracil(F),and oxaliplatin(OX)(FOLFOX)is routinely employed to treat several types of solid tumours in various tissues.However,F is characterized by large interpatient variability with respect to plasma concentration,which necessitates close monitoring during treatments using of this compound.Since plasma drug concentrations often do not reflect tissue drug concentrations,it is essential to utilize sample-preparation methods specifically suited to monitoring drug levels in target organs.In this work,in vivo solid-phase microextraction(in vivo SPME)is proposed as an effective tool for quantitative therapeutic drug monitoring of FOLFOX in porcine lungs during pre-clinical IVLP and intravenous(Ⅳ)trials.The concomitant extraction of other endogenous and exogenous small molecules from the lung and their detection via liquid chromatography coupled to high resolution mass spec-trometry(LC-HRMS)enabled an assessment of FOLFOX's impact on the metabolomic profile of the lung and revealed the metabolic pathways associated with the route of administration(IVLP vs.Ⅳ)and the therapy itself.This study also shows that the immediate instrumental analysis of metabolomic samples is ideal,as long-term storage at-80 ℃ results in changes in the metabolite content in the sample extracts.

The value of drug concentration and anti-drug antibody monitoring in biologic therapy for inflammatory bowel disease / 中华检验医学杂志

Inflammatory bowel disease (IBD) is a chronic relapsing autoimmune disorder of the gastrointestinal tract. In recent years, biologic agents have been widely used in the treatment of IBD, significantly ameliorating symptoms in affected individuals. However, immunogenicity of these medications remains a limiting factor in IBD biologic therapy. The appropriate drug concentration is of great significance in improving the efficacy of biological agents, reducing the production of anti-drug antibodies, and reducing adverse reactions. Therefore, monitoring drug trough concentrations and anti-drug antibody levels during treatment can optimize medication usage and facilitate more informed adjustments to treatment strategies. This article elaborates on the mechanism and reasons for the generation of anti-drug antibodies, as well as the significance, timing, effectiveness, and detection methods of drug concentration and anti-drug antibody monitoring. Thus, it underscores the value of drug concentration and anti-drug antibody monitoring in the context of biologic therapy for IBD.

Multi-centre survey and analysis of individual therapy of antimicrobial agents in children / 中国药房

OBJECTIVE To investigate the development of individual therapy of antimicrobial agents in pediatric patients. METHODS A questionnaire survey was conducted to investigate the individual therapy of antimicrobial agents in 30 children’s hospitals and pediatric departments of general hospitals in China. The survey data was analyzed statistically by Microsoft Excel 2007 and SPSS 26.0 software. RESULTS In this survey， 75 questionnaires were collected， and 53 of them were valid with an effective rate of 70.7%. The results showed that 86.7% （26/30） of the hospitals carried out individual therapy of antimicrobial agents in different forms. Clinical needs primarily contributed to the individual therapy in these hospitals， while the insufficient personnel and equipment were the biggest obstacles for individual therapy. The proportions of hospitals， who implemented evidence- based pharmacy， therapeutic drug monitoring （TDM）， model-informed precision dosing （MIPD） and antimicrobial-related genetic tests were 70.0%， 80.0%， 30.0% and 33.3%， respectively. Various detection methods of TDM were carried out in various hospitals， and the antimicrobial agents which needed TDM focused on vancomycin and voriconazole. Moreover， nearly half of pharmacists did not know much about MIPD. CONCLUSIONS At present， TDM is the main way to develop individual therapy of antimicrobial agents in various hospitals， but its monitoring coverage and testing standards need to be improved. MIPD and antimicrobial-related gene tests still need to be further promoted in clinical practice.