群体药代动力学在万古霉素治疗药物监测的应用

群体药代动力学(PPK)应用统计学原理,可综合评价影响药代动力学个体间及个体内差异的各种因素,并进一步利用Bayesian反馈,能较为准确地预测患者个体药代动力学参数。PPK在万古霉素治疗药物监测、给药方案设计调整及药动-药效研究中均有广泛应用。     

Pharmacokinetics of Vancomycin in Oncology Egyptian Paediatrics: A Dosage Adjustment Trial

The purpose of this study is to determine the pharmacokinetic parameters of vancomycin in Egyptian paediatric oncology patients and to evaluate the factors that influence the variability of the pharmacokinetic parameters in this population. Vancomycin serum concentration at steady state was determined in 51 paediatric cancer patients who were treated with vancomycin multiple intravenous infusions. Also individual vancomycin pharmacokinetic parameters were calculated assuming one compartment model. The mean vancomycin total body clearance and mean vancomycin volume of distribution were significantly higher among the age range of 2 to <12 years as compared with older age. Obese patients showed significant lower values of peak and trough vancomycin concentrations than those of normal and underweight patients. A significant correlation was found between the estimated creatinine clearance (Schwartz formula) and vancomycin total body clearance in the studied patients. Also, a significant direct correlation between vancomycin volume of distribution and ratio between blood urea nitrogen (mg/dl)/weight (kg) was found. As a conclusion, age and obesity were identified as the most important factors influencing vancomycin total body clearance, volume of distribution and serum concentrations in the studied patients.     

万古霉素治疗药物监测必要性的系统评价

目的 系统评价万古霉素(三环糖肽类抗生素)治疗药物监测(TDM)的必要性.方法 通过计算机检索、手工检索及向厂家索取资料,全面收集全世界范围内万古霉素治疗药物监测的随机对照研究,共纳入3个研究,总计332名患者.比较万古霉素TDM组和非TDM组在疗效和安全性方面的差异.结果 Meta分析结果表明,抗感染所需时间、感染控制累计剂量、肌酐清除率、肌酐水平、以及其他指标,TDM组和非TDM组比较均无显著性差异;但TDM组中,Cmax＞25 μg·mL-1亚组与Cmax<25 μg·mL-1亚组比较,用药时间、累计剂量和ClIP浓度2组均有统计学意义.结论 TDM组和非TDM组在疗效和安全性上均没有显著差异;但TDM组中,Cmax＞25μg·mL-1组与Cmax<25 μg·mL-1组比较,疗效和安全性均有显著性差异.     

万古霉素血药浓度监测回顾性分析

采用荧光免疫偏振法(FPIA)测定万古霉素血药浓度,结合临床病历、病原学检查、肾功能指标、合并用药及不良反应情况, 对我院2005年2月～2008年9月万古霉素血药浓度监测结果进行回顾性分析.以期为临床合理用药提供可靠依据,从而提高疗效和减少毒性的发生率. %;峰浓度﹥40 ·mL-1)范围内的占总监测数的88.94监测住院患者49例,万古霉素血药浓度235例次,结果显示:其中在治疗窗(5～40 μg%;谷浓度﹤5μg·mL-1,占总数的4.25%.性别对血药浓度无显著影响(P﹥0.05).年龄对血药浓度有显著影响(P﹤0.05).·mL-1,占总数的6.81     

Cytochrome P450 and therapeutic drug monitoring with respect to clozapine

Clozapine is an atypical antipsychotic drug that is mainly used for the treatment of refractory schizophrenia. Clozapine is eliminated by oxidation in the liver, predominantly by cytochrome P4501A2 (CYP1A2). Due to the influence of inhibitors, inducers and genetic factors on CYP1A2-activity, several studies have reported a very large interindividual variability in clozapine plasma concentrations at a fixed dose. A number of methods have been published for the measurement of clozapine and metabolites in plasma. Plasma concentrations are most frequently measured by high-performance liquid chromatography. Most methods measure clozapine and the main metabolite, norclozapine, whereas two methods measure clozapine and two metabolites. Several studies suggest that a minimum effective clozapine plasma concentration of >350 μg/l must be achieved in order to ensure acceptable clinical response, whereas the upper limit of the therapeutic interval not yet has been clearly defined. The occurrence of agranulocytosis, the most serious side-effect of clozapine treatment does not seem to be dose-related and it is not possible to predict which patients are at risk of developing agranulocytosis. The risk of central nervous system side-effects seems to increase with concentrations above 1300 μg/l. Monitoring of clozapine plasma concentrations is recommended during concomitant use of other drugs that are known to interact with the oxidation of clozapine, such as carbamazepine (inducer) or fluvoxamine (inhibitor). Overall, it is concluded that therapeutic drug monitoring may be of value in the clinical management of clozapine.     

Long-term therapeutic drug monitoring of clozapine and metabolites in psychiatric in- and outpatients

RATIONALE: Clozapine is a unique antipsychotic drug, outstanding for its lack of extrapyramidal side-effects and its superior efficacy in refractory schizophrenia. However, an unambiguous concentration-response relationship has not yet been established. OBJECTIVE: We investigated serum concentrations of clozapine, norclozapine and clozapine-N-oxide in psychiatric in- and outpatients to identify particular metabolic patterns in clozapine responders and non-responders and putative threshold levels for clozapine response. METHODS: Psychiatric assessments, CYP2D6 genotype, and weekly serum concentrations of clozapine, norclozapine and clozapine-N-oxide were obtained in 34 adult schizophrenic in-and outpatients (18 men, 16 women) during 10 weeks of clozapine treatment with a naturalistic dose design. RESULTS: Responders (n=21) displayed significantly lower serum concentrations of clozapine corrected for dose compared to non-responders (n=13; P<0.05), while none of the other parameters (absolute clozapine concentration, metabolite ratios, gender) were different. Smokers had significantly lower dose-corrected clozapine concentrations. A positive correlation was observed between age and average steady state clozapine concentrations. CONCLUSIONS: These findings indicate a possible link between CYP activity and response to clozapine that is not mediated through differences in serum concentrations. No clinically meaningful pattern in serum parameters could be identified that differentiates responders from non-responders. Thus, clozapine TDM seems ineffective for predicting clinical response. Smoking behavior is a major determinant of clozapine clearance while CYP2D6 genotype does not impact clozapine disposition.     

Vancomycin dosing and therapeutic drug monitoring practices: guidelines versus real-life

Background Correct dosing and therapeutic drug monitoring (TDM) practices are essential when aiming for optimal vancomycin treatment. Objective To assess target attainment after initial dosing and dose adjustments, and to determine compliance to dosing and TDM guidelines. Setting Tertiary care university hospital in Belgium. Method A chart review was performed in 150 patients, ranging from preterm infants to adults, treated intravenously with vancomycin. Patient characteristics, dosing and TDM data were compared to evidence-based hospital guidelines. Main outcome measures Target attainment of vancomycin after initial dosing and dose adjustments. Results Subtherapeutic concentrations were measured in 68% of adults, in 76% of children and in 52% of neonates after treatment initiation. Multiple dose adaptations (median 2, Q1 1–Q3 2) were required for target attainment, whilst more than 20% of children and neonates never reached targeted concentrations. Regarding compliance to the hospital guideline, some points of improvement were identified: omitted dose adjustment in adults with decreased renal function (53%), delayed sampling (16% in adults, 31% in children) and redundant sampling (34% of all samples in adults, 12% in children, 13% in neonates). Conclusion Target attainment for vancomycin with current dosing regimens and TDM is poor in all age groups. Besides, human factors should not be ignored when aiming for optimal treatment. This study reflects an ongoing challenge in clinical practice and highlights the need for optimization of vancomycin dosing strategies and improvement of awareness of all health care professionals involved.

     

某大型综合性医院呼吸科住院患者抗生素使用情况分析

目的：调查我国某大型综合性医院呼吸科住院患者抗生素的使用情况,以指导临床合理用药。方法：采用临床流行病学回顾性调查方法,收集2003年1月-2007年12月我国某大型综合性医院呼吸科所有住院感染患者的临床资料,统计分析感染性疾病种类、抗生素消耗量及相互间的关系。结果：该院呼吸科病房住院患者以下呼吸道感染为主,其他所占比例相对较少;抗生素用量最大为头孢菌素类／β内酰胺酶抑制剂,其次为青霉素类／β内酰胺酶抑制剂,碳青霉烯类及多肽类稳定在较低的水平;上呼吸道与下呼吸道感染与各类抗生素药物的限定日剂量频度存在差别;阿莫西林类药物利用指数值逐年升高,其他类抗生素药物利用指数值变化较为平稳。结论：该大型综合性医院呼吸科在临床经验性选择抗生素、抗生素使用策略方面基本合理,有效降低了病原菌的耐药水平。     

治疗药物监测临床应用现状

回顾治疗药物监测(TDM)的临床应用等,本文重点综述抗癫痫药物与免疫抑制药物的TDM临床应用评价,分析开展TDM过程中存在的问题。     

《中国万古霉素治疗药物监测指南(2020更新版)》解读

2020年12月,《中国万古霉素治疗药物监测指南(2020更新版)》发表于Clinical Infectious Diseases,该版指南严格遵循指南制定与更新的方法学规范,范围为接受万古霉素间断输注的成人、儿童及新生儿,更新类型为部分更新。该更新版指南的主要变化包括:①拓宽了需开展万古霉素治疗药物监测(TDM)的人群范围,如新生儿/儿童患者、接受肾脏替代治疗患者、中重度心力衰竭患者和肾功能亢进患者等;②修订了万古霉素TDM的参数,同时推荐24 h血药浓度-时间曲线下面积和谷浓度;③增加复测TDM的必要性与时机相关推荐意见;④增加肾功能不全、儿童及新生儿等特殊患者的初始剂量推荐。本文对更新版指南的推荐意见进行总结和解读,以促进该指南更好地实施推广。     

英夫利西单抗失应答的被动治疗药物监测在炎症性肠病治疗中的药物经济学系统评价

目的:英夫利西单抗(infliximab,IFX)用于炎症性肠病(inflammatory bowel disease,IBD)治疗可能出现药物失应答,对于IFX失应答,临床采用传统经验增加药物剂量策略或根据治疗药物监测(therapeutic drug monitoring,TDM)策略.为评价其经济性,本研究系统评...     

基于伏立康唑血药浓度监测的药物相互作用研究

目的 临床药师通过治疗药物监测(TDM)手段，研究利福平和伏立康唑之间的药物相互作用。方法 基于利福平和伏立康唑联用，及停用利福平后使用伏立康唑这两类患者的伏立康唑血药浓度监测情况，揭示利福平和伏立康唑间的药物相互作用强度与持续时间。结果 18例利福平和伏立康唑联用患者，94.44%患者的伏立康唑血药浓度低于有效治疗浓度范围下限(1.0mg/L)，其中72.22%患者低于定量下限0.16mg/L；19例停用利福平后再使用伏立康唑的标本中，停药6d内伏立康唑血药浓度小于1.0mg/L共12例，占总例数的63.16%，占停药6d内例数的91.67%；停药7d及以上伏立康唑血药浓度大于1mg/L的5例，占总例数的26.32%，占停药7d及以上例数的83.33%。结论 利福平会严重降低伏立康唑血药浓度，在停用利福平第7d起伏立康唑血药浓度很可能才上升有效浓度范围，因此临床上应避免伏立康唑与利福平联用。临床药师借助TDM成功干预了有临床意义的药物相互作用，TDM是临床药师参与药物治疗的有效技术手段。     

我院治疗药物监测的开展与结果分析

目的：通过对我院2000年91例治疗药物检测的结果分析，统计检测结果的合格率情况，以期对其它医院提供参考。方法：对我院现开展的氨茶碱，地高辛等检测项目的结果用百分数和平均浓度进行统计，结果：氨茶碱在正常范围的百分数为25．0％，地高辛为50％，结论：我院现开展的治疗药物检测结果不在治疗范围内的所占比例较大。     

某院90例万古霉素临床使用的合理性评价

目的:分析医院万古霉素临床使用的合理性,以便为万古霉素合理用药提供参考。方法:抽取2018年1月—2019年6月间收治的使用万古霉素治疗的住院患者90例资料作为研究对象,统计其患者治疗科室、临床诊断以及万古霉素用药相关信息等内容,分析其用药的合理性。结果:90例万古霉素使用患者中(除少数患者外)总体用药是合理的;合理用药主要表现在适应证(94.44%)、溶媒选择、用法用量、用药疗程、联合用药、病原学送检以及及时会诊方面。结论:医院万古霉素临床使用基本符合相关规定,但仍存在小部分不合理用药现象,医院应开展治疗药物监测(TDM),以确保患者万古霉素用药的合理性和安全性。     

甲氨蝶呤血药浓度与患者肝肾功能指标的相关性分析

目的：通过对22例次应用大剂量甲氨蝶呤（HD-MTX）化疗的急性淋巴细胞白血病（ALL）患者血药浓度监测、肝肾功能实验室检查数据进行分析总结,探讨 MTX 20 h 和44 h 血药浓度与 MTX 实验室肝肾功能指标之间的联系。方法对 ALL 患者应用 HD-MTX 化疗后20、44 h 进行血药浓度监测,患者 HD-MTX 化疗后进行血常规、肝肾功能、血糖、血脂、乳酸脱氢酶（LDH）等相关实验室检查,收集资料。采用 SPSS 19．0软件 Spearman 相关分析两变量之间的相关性。结果MTX 20、44 h 血药浓度与患者化疗后血肌酐（CRE）值呈正相关,而与血尿素氮（BUN）、尿酸（UA）值无关。MTX 20 h 血药浓度与患者化疗后血总胆红素（STB）、直接胆红素（DBIL）、谷丙转氨酶（ALT）、谷草转氨酶（AST）值均呈正相关,而44 h 血 MTX 浓度与 STB、DBIL、ALT、AST 值无相关性。结论MTX 20、44 h 血药浓度监测可以预测 MTX 化疗造成的肌酐升高型肾损害,而 MTX 20 h血药浓度监测对于 MTX 造成的肝损害也有一定的预测作用。     

老年患者万古霉素血药浓度监测与疗效评估

目的评估老年患者的万古霉素血药浓度、临床疗效及肾毒性。方法回顾性分析我院呼吸科用万古霉素并监测血药浓度的39例老年患者的临床资料。结果万古霉素的治疗有效率为82.05%;谷浓度在10~20 mg·L-1占48.12%,谷浓度<10 mg·L-1的19例患者中有6例进行了剂量调整,2例(5.13%)患者出现了肾毒性,万古霉素减量或停用后肌酸酐均恢复至基础水平。3例(7.69%)用药前肾功能不全的患者均未有肾毒性发生。万古霉素联用依替米星及利尿剂未发生肾毒性。结论老年患者用万古霉素时应调整剂量,并借助血药浓度的监测对万古霉素进行调整。     

202例次万古霉素血药浓度监测与临床应用分析

目的 分析万古霉素血药浓度监测结果及临床应用情况,为临床合理用药提供参考。方法 采用反相-高效液相色谱法测定万古霉素血药浓度,对万古霉素血药浓度监测结果及相关用药信息进行比较分析。结果 万古霉素谷浓度监测202次,平均血药谷浓度（14.36±8.12）mg/L,浓度小于10 mg/L的有68例次（33.66%）,在10～20 mg/L的有100例次（49.51%）,大于20 mg/L的有34例次（16.83%）;肾功能正常与异常组间,血药谷浓度有显著性差异;用药前后,各项肾功能指标无显著性差异。结论 万古霉素个体差异大,需加强血药浓度监测;针对肾功能异常患者,临床医生和药师需审慎评估给药剂量;临床医生应根据血药浓度及时调整用药方案,实现个体化给药。     

胸腔内注射阿霉素治疗恶性胸腔积液的药物浓度监测和药效学研究

以荧光光谱法对胸腔内注射国产阿霉素治疗恶性胸腔积液患者的血液、胸水中的药浓度进行监测和药效对比研究。研究表明：胸腔内注射４０ｍｇ阿霉素后，９例患者２ｈ的平均血、胸水药浓度分别为６５ｎｇ／ｍｌ，５９μｇ／ｍｌ，比值为１∶８２９，其它时间的胸水药浓度高于相同时间的血药浓度数百倍（Ｐ＜０．０５）。在１２例的疗效评价中，显效率３３．３％，有效率５０％，未发生骨髓抑制、心肌损害等严重毒副反应。