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.

El papel de los esquemas cognitivos y la adversidad infantil en la probabilidad de desarrollar un trastorno depresivo mayor / The role of cognitive schemas and childhood adversity in the likelihood of developing Major Depressive Disorder

Abstract Introduction/objective: Major Depressive Disorder (MDD) is a multifactorial mental health disorder. Stressful events and childhood abuse have been included in different models to explain its etiology. However, little evidence is available on how attributional style and early maladaptive schemas are related to MDD. Method: A retrospective case-control study using a three-stage hierarchical logistic model was conducted to explore the relationship between MDD and psychosocial variables such as childhood adversity, stressful life events, attributional style, and cognitive schemas in a sample of 171 individuals with a current depressive episode and 171 healthy controls. Results: Depression could be predicted by childhood adversity, an attributional style characterized by interpreting stressful events as negative and uncontrollable and the cognitive schemas in impaired autonomy/performance domains and impaired limits. Conclusions: Our results highlight the relevance of identifying cognitive factors, beyond clinical symptoms that could be useful to better understand MDD. These findings may result in better preventive programs and create awareness of the role of cognitive domains in MDD.

Resumen Introducción/objetivo: el trastorno depresivo mayor (TDM) es un trastorno de salud mental de origen multifactorial. Los eventos estresantes y el maltrato infantil se han incluido en diferentes modelos para explicar su etiología. Sin embargo, hay poca evidencia disponible sobre cómo el estilo atribucional y los dominios de esquemas maladaptativos tempranos se relacionan con el TDM. Método: Se realizó un estudio retrospectivo de casos y controles utilizando un modelo logístico jerárquico de tres etapas para explorar la relación entre el TDM y variables psicosociales como la adversidad infantil, los eventos estresantes, el estilo atribucional y los esquemas cognitivos en una muestra de 171 individuos con un episodio depresivo actual y 171 controles sanos. Resultados: La depresión podría predecirse por la adversidad infantil, un estilo atribucional caracterizado por interpretar los eventos estresantes como negativos e incontrolables y los esquemas cognitivos en los dominios de autonomía/desempeño y límites deteriorados. Conclusiones: Nuestros resultados resaltan la relevancia de identificar factores cognitivos, más allá de los síntomas clínicos, que podrían ser útiles para alcanzar una mejor comprensión del trastorno. Estos hallazgos favorecen el diseño de programas de prevención que enfaticen en el rol de los esquemas cognitivos.

Place de la tomodensitométrie dans la prise en charge des occlusions intestinales aigues à Dakar / Place of tomodensitometry in the management of acute intestinal occlusions in Dakar

ntroduction : L'occlusion intestinale aiguë (OIA) est un syndrome défini par l'arrêt du transit intestinal provoqué par un obstacle ou par une paralysie du péristaltisme intestinal. Il s'agit d'une urgence diagnostique et thérapeutique. Le scanner multibarrette a révolutionné la prise en charge de cette pathologie, car permettant de répondre aux différentes questions du chirurgien.Le but de notre étude était de décrire les aspects scanographiques des OIA, de déterminer les étiologies et de montrer la place de la TDM dans la prise en charge des OIA. Matériel et Méthode : Il s'agissait d'une étude rétrospective descriptive réalisée sur 05ans (Janvier 2010 à décembre 2015) portant sur 81 dossiers de patients colligés dans les services d'imagerie du CHU Aristide Le Dantec et de l'hôpital Principal. Les dossiers retenus sont ceux dont le diagnostic était établi à partir de la clinique, de l'imagerie et/ou non de la chirurgie. Résultats : Les occlusions mécaniques représentaient 94,4% (76 cas) et fonctionnelles 5.6% (05 cas). Elles étaient de type grêle dans 70% des cas et colique dans 30%. Les lésions élémentaires mises en évidence étaient : zone transitionnelle (36 patients), signe du fèces (28 patients), signe du bec (06 patients), signe du tourbillon (11 patients), signes de gravité (36 patients). Soixante-douze patients ont bénéficié d'une chirurgie et 04 patients d'un traitement médical. Le diagnostic préopératoire était confirmé par la chirurgie chez 68 patients. La chirurgie a redressé le diagnostic dans 04 cas. Les signes de gravité étaient confirmés à la chirurgie chez tous nos patients. Conclusion : La TDM occupe une place prépondérante dans le choix thérapeutique des OIA. Elle doit être demandée en première intention devant un syndrome occlusif

Introduction: Acute intestinal obstruction (AIO) is a syndrome defined by the cessation of intestinal transit caused by an obstacle or paralysis of intestinal peristalsis. It is a diagnostic and therapeutic emergency. The multi-bar CT scan has revolutionized the management of this pathology, as it allows the surgeon to answer different questions. The aim of our study was to describe the CT aspects of AIO, to determine the etiologies and to show the place of CT in the management of AIO. Material and Method: This was a retrospective descriptive study conducted over 5 years (January 2010 to December 2015) on 81 patient files collected in the imaging departments of the CHU Aristide Le Dantec and the Hôpital Principal. The files retained were those whose diagnosis was established from the clinic, imaging and/or not from surgery. Results: Mechanical occlusions represented 94.4% (76 cases) and functional occlusions 5.6% (05 cases). They were of the small bowel type in 70% of cases and colonic in 30%. The elementary lesions found were: transitional zone (36 patients), feces sign (28 patients), beak sign (06 patients), whirlpool sign (11 patients), signs of severity (36 patients). Seventytwo patients received surgery and 04 patients received medical treatment. The preoperative diagnosis was confirmed by surgery in 68 patients. Surgery corrected the diagnosis in 04 cases. Signs of severity were confirmed at surgery in all our patients. Conclusion: The CT scan has a major role in the therapeutic choice of AIO. It should be requested in first intention before an occlusive syndrome

Target-responsive subcellular catabolism analysis for early-stage antibody-drug conjugates screening and assessment

Events including antibody‒antigen affinity, internalization, trafficking and lysosomal proteolysis combinatorially determine the efficiency of antibody-drug conjugate (ADC) catabolism and hence the toxicity. Nevertheless, an approach that conveniently identifies proteins requisite for payload release and the ensuing toxicity for mechanistic studies and quality assessment is lacking. Considering the plethora of ADC candidates under development, we developed a target-responsive subcellular catabolism (TARSC) approach that examines ADC catabolism and probes changes in response to targeted interferences of proteins of interest. We firstly applied TARSC to study the commercial T-DM1 and the biosimilar. We recorded unequivocal catabolic behaviors regardless of the absence and presence of the targeted interferences. Their negligible differences in TARSC profiles agreed with their undifferentiated anti-tumoral efficacy according to further

Therapeutic drug monitoring in the individualized administration of cyclosporin A: Application and research progress / 中国临床药理学与治疗学

Cyclosporine A (CsA) is a kind of cellular immunosuppressant, which is widely used in organ transplantation, blood diseases and autoimmune diseases. Because of its poor oral bioavailability, individual differences and prone to adverse reactions, so clinical therapeutic drug monitoring (TDM) and individual administration of CsA can ensure its safety and effectiveness. However, the treatment window of CsA is narrow, and its blood concentration is affected by age, sex, diet, drug factors, genetic factors and so on. Therefore, combined with the literature reports at home and abroad, this paper reviews the research on the application of TDM and individual drug administration of CsA, in order to provide more valuable reference for clinical safe and rational drug use.

Apport de la TDM thoracique pour le dépistage de la COVID-19 et impact médico-économique de la pandémie à COVID-19 au service de radiologie de Fann (Dakar-Sénégal) / Contribution of thoracic CT for COVID-19 screening and medico-economic impact of the COVID-19 pandemic in the radiology department of Fann (Dakar-Senegal)

Objectifs :Évaluer l'apport de la TDM thoracique dans le diagnostic des patients suspects de COVID-19en comparaison avec la technique de référence (RT-PCR) et déterminer l'impact médico-économique de la COVID-19 au service de radiologie du CHU de Fann. Matériels et méthodes: Il s'agissait d'une étude rétrospective, descriptive sur une période de 4 mois allant du 1er avril au 31 Juillet 2020, au service de radiologie du CHU de Fann.Ont été inclus les patients reçus pour suspicion clinique de COVID-19, qui avaient eu une TDM thoracique et un prélèvement naso-pharyngé par écouvillonnage pour RT-PCR, soit au total 314 patients. Nous avons étudié les données épidémiologiques, cliniques, les images évocatrices de COVID-19 (opacités en verre dépoli, condensation, topographie lésionnelle), existence ou non d'une embolie, les anomalies en faveur de surinfection, les lésions associées, l'impact sur la fréquentation des différentes modalités etl'impact sur les recettes. Résultats:L'âge médian était de 62 ans et le sex-ratio 1,61. La fièvre a été présente chez 7 patients (2,23%); la toux chez 17 patients (5,41%); la dyspnée chez 30 patients (9,55%) et un syndrome de détresse respiratoire chez 63 patients (20,07%). La clinique n'a pas été précisée chez 163 patients (51,91%). La TDM thoracique était normale chez 20 patients (6,37%), évocatrice de COVID-19 chez 274 patients (87,26%) et non évocatrice de COVID-19 chez 20 patients (6,37%). La RT-PCR était positive chez 125 patients soit 39,80%. La sensibilité et la spécificité de la TDM étaient respectivement de 91,2% et 15,34%. La valeur prédictive positive, la valeur prédictive négative et le taux de précision étaient respectivement de 42%, 72,5% et 45,5%. La baisse du taux de fréquentation était de 59% en radiographie standard, 55% en échographie, 24% au scanner et 87% en mammographie. Dans notre étude on a noté une baisse de 40% des recettes au second trimestre de 2020 comparativement au premier trimestre. Conclusion: La TDM thoracique a une bonne sensibilité pour le diagnostic de la COVID-19. De ce fait, elle peut être considérée comme un outil principal pour la détection des lésions pulmonaires évocatrices de pneumonie COVID-19. Les impacts médico-économiques de la COVID-19 ont été considérables.

Evaluation of hormonal and metabolic factors related to depression in reproductive age women / Evaluación de factores hormonales y metabólicos relacionados con la depresión en mujeres en edad fértil

Abstract Introduction Major depressive disorder (MDD) is a prevalent disease affecting women more than men worldwide. Various factors are involved in the genesis of depression, including hormones such as testosterone and certain metabolic factors Objective To evaluate hormone levels and metabolic variables in women with major depression and healthy controls. Method A cross-sectional, comparative analytical study was conducted in 40 participants, 23 patients with an MDD diagnosis and 17 controls, all of women in reproductive age between the ages of 18 and 45. Sociodemographic variables, hormonal profile, and metabolic variables were assessed and the 17-item Hamilton Depression Scale was used to evaluate depressive symptoms. Results No statistically significant differences were observed between the groups in the hormonal and metabolic variables explored. Nevertheless, it was observed that the lower the testosterone levels and the higher the serum glucose levels, the more intense depressive symptoms were. Discussion and conclusion Testosterone is associated with a lower depressive symptoms score on the Hamilton Depression scale, suggesting a potential antidepressant effect, whereas high glucose levels are associated with a higher score on this scale. We believe that the measurement of hormonal and metabolic variables in women can contribute to a better understanding of the pathophysiology of depression.

Resumen Introducción El trastorno depresivo mayor (TDM) es una enfermedad prevalente a nivel mundial, que afecta más a mujeres que a hombres. En la génesis de la depresión se consideran diversos factores, entre ellos algunas hormonas como la testosterona y ciertos factores metabólicos Objetivo Evaluar los niveles de hormonas y variables metabólicas en mujeres con depresión mayor y controles sanas. Método Se realizó un estudio transversal, comparativo y analítico en 40 participantes, 23 pacientes con diagnóstico de TDM y 17 controles, todas ellas mujeres de 18 a 45 años en periodo reproductivo. Se evaluaron variables sociodemográficas, perfil hormonal y variables metabólicas, y se aplicó la Escala de Depresión de Hamilton de 17 reactivos para evaluar los síntomas depresivos. Resultados No se observaron diferencias estadísticamente significativas entre los grupos en las variables hormonales y metabólicas exploradas. Sin embargo, se observó que, cuanto menores eran los niveles de testosterona y mayores los de glucosa sérica, los síntomas depresivos eran de mayor intensidad. Discusión y conclusión La testosterona se asocia con un menor puntaje de síntomas depresivos en la Escala Hamilton, lo que sugiriere un potencial efecto antidepresivo, mientras que los niveles altos de glucosa se asocian con un mayor puntaje en dicha escala. Consideramos que la medición de variables hormonales y metabólicas en la mujer puede contribuir a mejorar el conocimiento de la fisiopatología de la depresión.

Anti-HER2 Antibodies In Combination With Chemotherapy Or Chemotherapy-Free Regimens Targeting Her2-Positive Breast Cancer: A Systematic Review

@#Breast cancer is the leading cause of cancer-related death in female worldwide. Human epidermal growth factor receptor 2 (HER2) amplification is observed in approximately 20% of breast cancer cases and is associated with poor clinical outcomes. Dual HER2 blockade without chemotherapy represents an attractive therapeutic approach, and it remains unresolved if anti-HER2 therapeutic antibodies are sufficient to replace chemotherapy regimens. In this review, we discuss the approved therapeutic monoclonal antibodies (pertuzumab and trastuzumab) and antibody-drug conjugate (trastuzumab emtansine or T-DM1) for the treatment of HER2-positive breast cancer patients. In summary, phase II and III clinical trials have demonstrated that dual HER2 blockade (pertuzumab and trastuzumab) plus chemotherapy regimens confer better efficacy compared with dual HER2 blockade alone, or anti-HER2 antibody monotherapy, in HER2-positive breast cancer patients. Dual HER2 blockade (pertuzumab and trastuzumab) combined with chemotherapies (5-fluorouracil, epirubicin, cyclophosphamide and docetaxel) yield superior response. Moreover, dual HER2 blockade (T-DM1 and pertuzumab) in combination with docetaxel represents a promising treatment regimen containing T-DM1. Ongoing clinical trials are assessing the optimal chemotherapy of choice with anti-HER2 antibodies combinations. In conclusion, improved outcomes are attributable to selection for the optimal chemotherapy regimen in combination with anti-HER2 antibodies instead of replacing chemotherapy altogether with the current line of anti-HER2 therapeutic antibodies.

Modifications to a Drug Ordering System Improved the Implementation Rate of Therapeutic Drug Monitoring for Voriconazole / 医薬品情報学

Introduction: Voriconazole (VRCZ) is a triazole antifungal agent for which therapeutic drug monitoring (TDM) is recommended. At Juntendo University Hospital, the VRCZ TDM implementation rate was 42% between January 2011 and October 2017. Here, we report that modifications to the hospital’s drug ordering system improved the implementation rate of VRCZ TDM.Method: In August 2018, the drug ordering system was modified so that a message appeared on the screen to notify clinicians of the need to monitor VRCZ blood concentrations and to recommend a date for sample collection. In addition, the laboratory orders for VRCZ levels were digitized. We compared two one-year periods before and after implementation of the modifications (August 2017 to July 2018 and August 2018 to July 2019) to verify the effect of the changes.Result: Results showed an increase in the TDM implementation rate: 12 patients (42.8%) received TDM before modification of the system, and 26 patients (92.9%) received TDM after modification of the system. Further, the rate of blood sampling at the recommended time point for estimating blood concentration (day 5-7 after the start of administration) improved after system modification, i.e., blood samples were collected from 18 patients (64.3%) at the steady state point. In contrast, blood samples were collected from only 6 patients (21.4%) before system modification. When blood concentrations deviated from the target range in patients who received TDM, clinicians took appropriate actions, such as reducing drug doses, prescribing drug holidays, or discontinuing medications.Conclusion: A system that provides information related to VRCZ blood concentration measurements can help clinicians provide patients with optimal pharmacotherapy.

Therapeutic drug monitoring of phenytoin using high performance liquid chromatography in a tertiary care hospital of Kashmir, India

Background: Phenytoin is the most commonly used anti-epileptic drug (AED) in this set up due to cost effectiveness and easy availability. Significant fluctuations in serum phenytoin levels leading to toxicities or treatment failures make it an ideal candidate for therapeutic drug monitoring (TDM).Methods: Patients of age ?18 years who were put on phenytoin were enrolled in this study. Estimation of serum phenytoin levels was done using HPLC. Data was analysed using SPSS version 20.0. Chi square test, Kruskal Wallis test were used to analyse the data.Results: A total of 105 patients enrolled in the study, twenty patients (19%) had normal or therapeutic serum phenytoin levels. Thirty-nine patients (37.2%) had sub therapeutic serum phenytoin levels, while forty-six patients (43.8%) had toxic serum phenytoin levels.Conclusions: The TDM of phenytoin should adopt a multi-disciplinary approach with active involvement of neuro-physicians, pharmacologists, pharmacists and other technical staff for improving the overall management of epilepsy. TDM data will provide the clinicians with greater insight into the factors determining the patient’s response to drug therapy.

Survey on the Development of Therapeutic Drug Monitoring in Chinese Hospitals in 2018 / 中国药学杂志

OBJECTIVE: To understand the development of therapeutic drug monitoring (TDM) in domestic hospitals and provide guidance for disciplinary development. METHODS: A range of professions involved in 7 aspects (33 questions) of TDM were surveyed by questionnaire on WeChat in late 2018. Information gathered included: basic information, development of TDM laboratories and clinical departments, monitoring drug types and quantity, quality control, interpretation of reports and individual drug regimen, and approval and management. These data were exported in Excel, and the valid data were included. RESULTS: Five hundred and four responses were received, of which 463 were valid and included, of which 177 hospitals developed TDM. The results of the above 7 aspects which were from those 177 hospitals in 2018 were summarized as follows. The educational backgrounds were mainly the master degree (43%) and the bachelor degree (33%). Most hospitals (75%) established chromatographic methods. The monitoring items were mainly blood drug concentration test(63%) and drug genetic testing (36%). In all clinical departments, TDM was most applied in Neurology. Eleven categories of drugs applying TDM in 2018 were investigated, of which psychotic drugs with the most varieties included eighteen drugs, and immunosuppressive agents had the most samples monitoring (57%). Over one half of hospital (64%) carried out the quality control. Only one half of hospitals (89/177) developed clinical interpretation, of which 75% showed that clinical pharmacists participated in the interpretation; 82% developed individualized plans based on the results. Most hospitals (65%) carried out the TDM review and the systems of examination and approval, and TDM in 47% of the hospitals was included in the hospital pharmacy management and drug therapy committee management system. CONCLUSION: This survey has obtained information of the seven aspects, and has mastered the TDM profile of 11 categories of drugs in 2018. However, there is still insufficient development in the quality control, clinical interpretation, individualized regimen development and TDM management. In addition to conducting drug monitoring, TDM work in the future will focus on improving and developing the above deficiencies and promoting clinical rational drug use.

Application of HPLC-MS/MS Method in the Determination of Whole Blood Concentration of Tacrolimus in Bone Marrow Transplant Patient / 现代检验医学杂志

Objective To develop a HPLC-MS/MS method for determination of Tacrolimus(FK506) in bone marrow trans plant patient,and explore the relationship of HPLC-MS/MS with CMIA and Elecsys in the measurement of FK506 blood drug concentration,and provide reliable basis for clinical rational use of monitoring method in FK506 blood drug concentra tion.Methods The separation was performed on a Ultimate xB-C18 column with a mobile phase of water (containing 2 mmol/L ammonium acetate and 0.1 ml/dl formic acid) and methanol (containing 0.1 ml/dl formic acid).The way of eluting was gradient.Mass spectrum detection method was ESI positive ion mode and the MRM transitions of FK506 m/z 821.5～ 768.5 and Ascomycin m/z 809.4～756.4.Selected part of the whole blood samples of FK506 in bone marrow transplant patient and respectively were tested by HPLC/MS/MS method,CMIA method and Elecsys method.Then,three methods for the detection of FK506 density were compared.Results The standard curve of FK506 was linear over the range of 0.5～50 ng/ml,Y=0.228X-0.003 08 (r=0.999 0).FK506 blood concentrations were not significantly different in HPLC/MS/MS method,CMIA method and Elecsys method.Conclusion The HPLC-MS/MS method in the detection of FK506 was established and can be used for monitoring of whole blood concentration of FK506 in bone marrow transplant patients.

Determination of Imatinib and Dasatinib in Leukemia Patients Plasma by HPLC-MS/MS / 现代检验医学杂志

Objective To develop a HPLC-MS/MS method for determination of Imatinib and Dasatinib in CML patient,and make it used in clinic trial.Methods The separation was performed on a Ultimate XB-C18 column with a mobile phase of water(containing 2 mmol/L ammonium acetate and 0.1 ml/dl formic acid)and methanol(containing 0.1 ml/dl formic acid). The way of eluting was gradient.Mass spectrum detection method was ESI positive ion mode and monitoring Imatinib m/z 494.5>394.3 and Dasatinib m/z 488.3>401.3.Results The standard curve of Imatinib was linear over the range of 0.05~7.5 μg/ml,Y =5.6×105 X+5× 103 (R =0.999 8).Thestandard curve of Dasatinib was linear over the range of 5~250 ng/ml,Y =211X+66.6(R=0.999 6).The relative recovery was among the range of 90%~107%.RSDs of intra-and inter-day validation were less than 10%.Conlusion This method is convenient,accurate and rapid,and can be used for the deter-mination of Imatinib and Dasatinib in clinic test.

The Comparison Survey between TDM Guideline and TDM Analysis Software Related to Setting the Initial Dose of Vancomycin Aimed to Utilize the TDM Guideline / 医薬品情報学

<b>Objective: </b>We have used therapeutic drug monitoring (TDM) analysis software to set the initial dose of vancomycin in our hospital.  In contrast, the TDM guideline, in which the initial dose of vancomycin per body weight was set, was published in 2012.  We looked forward with utilizing the TDM guideline in the clinical setting, after which we conducted multiple surveys to determine the important points of the TDM guideline.<br><b>Methods: </b>We surveyed patients treated with vancomycin, in whom the initial dose was set using the TDM analysis software and the concordance rate between the vancomycin dose set with the software and that set with the TDM guideline.<br><b>Results: </b>The concordance rate of vancomycin dose was 42.1%.  The mean age of the high-dose group (vancomycin dose higher than that recommended by the TDM guideline), was younger than that of the recommended-dose group.  Additionally, the mean body weight of the high-dose group was significantly lower than that of the recommended-dose group.  The corrected creatinine clearance of the low-dose group was significantly lower than that of the recommended-dose group.<br><b>Conclusion: </b>Our results suggest that when the initial dose is set after referring the TDM guideline in patients who are not very high age, and having low body weight and decreased renal function, the dose may differ from the dose set by using TDM analysis software.  In addition, since the recommended dose per body weight is a range and not a single value, setting the dose appropriate to target trough concentration is necessary.

Biological effects of trastuzumab and T-DM1 on different breast cancer lines / 中国药学杂志

OBJECTIVE: To investigate the different biological effects of trastuzumab and T-DM1 on BT-474 and HCC1954 cell lines. METHODS: Flow cytometry was employed to study the expression level of HER2 on the two cell lines. ELISA was used to check the binding ability of trastuzumab and T-DM1 with HER2 antigen. With cell proliferation inhibition and killing methods, the dose-response curves were explored to demonstrate the biological effects of trastuzumab and T-DM1 on the two cell lines. RESULTS: HER2 were highly expressed in both of the two cell lines. The HER2 binding ability was highly similar between trastuzumab and T-DM1. Trastuzumab could inhibit the proliferation of BT474 but not HCC1954, while T-DM1 could kill both kinds of cells. CONCLUSION: In the in vitro cell models, T-DM1 can play biological effect in HER2 highly expressed but trastuzumab-resistant cell lines.

The evaluation and analysis on the results of voriconazole plasma concentration monitoring / 药学实践杂志

Objective To clarify the necessity of therapeutic drug monitoring (TDM ) of voriconazole ,and give relevant clinical tips ,by comparing the plasma concentration of different clinical specialties before and after adjustment of dose .Methods This is a retrospective study of voriconazole TDM data .It involves 435 cases voriconazole plasma trough concentration meas-urement results of 154 inpatients to make a preliminary assessment .Results 4 .3% plasma concentration were higher than 5 .5 μg/ml ,26 .5% plasma concentration were less than 1 .0 μg/ml in renal transplantation department ;while 52 .3% plasma concentration were higher than 5 .5 μg/ml ,no less than 1 .0 μg/ml in infectious disease department .Conclusions Therapeutic drug monitoring is necessary for rational use of voriconazole .The majority of plasma concentrations in renal transplantation pa-tients were <1 .0 μg/ml ,lower than recommended treatment concentration range ;while most infectious disease patients have> 5 .5 μg/ml ,higher than recommended treatment concentration range .Clinical pharmacists can be more closely involved in the clinical use of voriconazole based on the results of the therapeutic drug monitoring .

Evidence-based medicine for trough serum concentration of vancomycin in Chinese adults / 中国生化药物杂志

Objective To systematically review articles about therapeutic drug monitoring of vancomycin in Chinese adults, so as to provide a reference of vancomycin trough concentrations for clinical evidence-based medicine.Methods Literature concerning vancomycin therapeutic drug monitoring were electronically retrieved in, CBM, Wanfang data, CNKI and Vip.Furthermore, the articles written in English by Chinese author in PubMed, EMbase were included.All the data were searched from inception of the database or network to Aug.2014.Two reviews independently screened literature according to the inclusion and exclusion criteria, and assessed the quality of literature using the Combieg and NOS.Analyzing the types of studies, the number of therapeutic monitoring of vancomycin, trough serum concentration, clinical outcome and renal function.Results A total of 35 studies including 32 cross-sectional studies and 3 cohort studies were included, all studies were observational studies.3099 patients with 5206 blood concentrations monitoring results were eligible for final analyses in all 32 cross-sectional studies.The rates of trough serum concentration in 5-15 mg/L was 53.6%.Compared with the trough concentrations between 5 and 15 mg/L, clinical cure rate was no significant difference in the trough concentrations of over 15μg/mL.However, the incidence rate was significantly reduced in renal toxicity in 5-15 mg/L trough serum concentration.Conclusions For adults, trough serum concentration of vancomycin should adopt the 5-15 mg/L in China.However, considering lack of high-level evidence, so it needs to be studied further.

Simultaneous determination of cyclosprine a, tacrolimus, sirolimus, mycophenolic acid, and prednisolone by UPLC-MS/MS / 中国药学杂志

OBJECTIVE: To establish an UPLC-MS / MS method for simultaneous determination of a variety of drugs used for im¬munosuppressive therapy in the whole blood of renal transplant patients and to use this method for blood concentration monitoring in therapeutic: drug monitoring.

Lack of association between plasma levels of non-nucleoside reverse transcriptase inhibitors & virological outcomes during rifampicin co-administration in HIV-infected TB patients.

Background & objectives: Among patients with HIV-associated tuberculosis (TB), reduced plasma non-nucleoside reverse transcriptase inhibitors (NNRTI) concentrations during rifampicin (RMP) co-administration could lead to HIV treatment failure. This study was undertaken to examine the association between plasma nevirapine (NVP) and efavirenz (EFV) concentrations and virological outcomes in patients infected with HIV-1 and TB. Methods: This was a nested study undertaken in a clinical trial of patients with HIV-1 and TB, randomized to two different once-daily antiretroviral treatment (ART) regimens along with anti-TB treatment (ATT). Trough concentrations of plasma NVP and EFV were estimated at months 1 (during ATT and ART) and 6 months (ART only) by HPLC. Plasma HIV-1 RNA level >400 copies/ml or death within 6 months of ART were considered as unfavourable outcomes. Genotyping of CYP2B6 516G>T polymorphism was performed. Results: Twenty nine per cent of patients in NVP arm had an unfavourable outcome at 6 months compared to 9 per cent in EFV arm (P<0.08). The mean NVP and EFV levels estimated at 1 and 6 months did not significantly differ between favourable and unfavourable responders. Logistic regression analysis showed CYP2B6 516G>T polymorphism significantly associated with virologic outcome in patients receiving EFV–based regimen. Interpretation & conclusions: Trough plasma concentrations of NVP and EFV did not show any association with response to ART in patients on ATT and once-daily ART. CYP2B6 516G>T polymorphism was associated with virologic outcome among patients on EFV.

A novel HER2-targeted drug:T-DM1 antibody-drug conjugate / 中国肿瘤临床

T-DM1 is a novel antibody-drug conjugate that has similar biological activity with that of trastuzumab. T-DM1 specifically delivers DM1, the effective anti-microtubule drug, into the cytoplasm of tumor cells with HER2 overexpression. The efficacy of T-DM1 monotherapy is better than lapatinib in combination with capecitabine and T-DM and is expected to become the standard second-line treatment for HER2-positive advanced breast cancer drugs. Clinical trials that compare T-DM1 with trastuzumab joint taxane as the first-line of treatment for advanced breast cancer trials are currently being performed. T-DM1 is a brand new anti-HER2 drug after trastuzumab. U.S. FDA already approved T-DM1 as a drug for the treatment of HER2-positive advanced breast cancer patients.