神经精神药理学治疗药物监测共识指南:2017版

治疗药物监测(Therapeutic Drug Monitoring,TDM)通过定量测定和解释血药浓度以优化药物治疗.TDM着眼于药代动力学的个体差异,使个体化药物治疗成为可能.在精神病学和神经病学领域中,有可能明显获益于TDM的主要患者群体包括少年儿童、孕妇、老年患者、智障患者、药物滥用者、涉法精神病患者、已知或怀...     

治疗药物监测

<正>治疗药物监测(therapeutic drug monitoring, TDM)是近代临床药物治疗学重大进展之一。目前 TDM已发展成为专门的学科,有关治疗药物监测的杂志、专著和论文逐年增多。国际治疗药物监测和临床毒理学会每两年都要召开一次国际会议,2005 年4月将在美国召开第9届大会。药物监测的范围     

抗肿瘤药物的治疗药物监测研究

尽管治疗药物监测(TDM)已广泛应用于多个疾病治疗领域,但在抗肿瘤药物方面的应用仍较为局限。近年来,抗肿瘤药物的暴露量与其疗效和药物不良反应之间的相关性研究越来越多,这有利于抗肿瘤药物个体化精准给药。本文综述了细胞毒类和靶向性(小分子和大分子)抗肿瘤药物的治疗药物监测现状,为肿瘤药物个体化用药提供参考。     

蛋白酶抑制剂的治疗药物监测

大量临床试验发现，蛋白酶抑制剂（PIs)血药浓度与药理效应，毒性及耐药密切相关，其药代动力学存在个体差异。同时又初步表明血药浓度监测有助于肝功能不全患者的剂量调整，因此，PIs的治疗药物监测（TDM）对PIs在HIV感染治疗中具有重要作用。但要充分发挥其作用，必须对分析方法，合适的目标浓度和治疗范围，最能预示药理效应的参数，血药浓度的精确解释等方面进行完善，同时需随机，有对照的临床试验评估TDM的临床实用性。     

2000～2004年我院4种抗癫痫药物血药浓度监测结果分析

目的：通过对4种抗癫痫药血药浓度有效率和高于及低于有效浓度的百分率的统计分析，有针对性的指导临床，合理调整给药方案。方法：运用回顾性调查方法，对解放军总医院2000年1月～2004年12月所监测的4种抗癫痫药物的血药浓度结果进行分析。结果：4种药物的监测结果中，有效血药浓度范围内结果占年监测例次的百分率以卡马西平为最高，但总体上均较低；而低于有效浓度范围的结果在年监测例次中所占比例较大。结论：血药浓度监测结果是指导临床用药的依据之一，应综合分析患者的用药方案、用药史、实验室数据和临床疗效．真正做到个体化给药。     

新免疫抑制剂的治疗药物监测

随着器官移植技术的发展和广泛应用,免疫抑制剂受到越来越多的关注。免疫抑制剂通过抑制淋巴细胞的功能,减少移植排斥反应的发生,延长移植物存活时间。但由于本身具有较强的毒性,尤其是肾毒性,因此常常需要在低剂量发生移植排斥和高剂量产生毒性之间取得平衡。除了经典的如肾上腺皮质激素、环磷酰胺、硫唑嘌呤等细胞毒药物外,新一代免疫抑制剂环孢素A、霉酚酸脂、他克莫司、西罗莫司等由于其治疗窗窄,即治疗浓度与中毒浓度接近;药代动力学存在明显的个体内及个体之间的差异,因此需要密切监测药物浓度,以确保药物处于有效治疗范围,且不易中…     

Cyclosporin monitoring in Australasia: 2002 update of consensus guidelines

Therapeutic drug monitoring of cyclosporin (CsA) has been established as part of the routine clinical treatment of patients following organ transplantation for more than 20 years, and based on contemporary knowledge, many consensus guidelines have been published to assist clinics and laboratories attain optimal strategies for patient care. This article addresses the newer directions in CsA monitoring, with particular reference to the Australasian situation that has evolved since the 1993 Australasian guideline. These changes have included the introduction of alternative assay methodologies, changed CsA formulation from Sandimmun to Neoral throughout Australasia, and alternatives to trough concentration (C0) monitoring, especially 2-hour concentration (C2) monitoring and associated validated dilution protocols to accurately quantitate the higher whole blood CsA concentrations. The revision was prepared following a recent survey of all Australasian CsA-monitoring laboratories where discordant practices were evident.     

《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。     

Pharmacovigilance in psychiatry: pharmacogenetic tests and therapeutic drug monitoring are promising tools

Contraceptive management in women with epilepsy is critical owing to the potential maternal and fetal risks if contraception or seizure management fails. This article briefly describes the pharmacokinetic interactions between antiepileptic drugs (AEDs) and hormonal contraceptives and the rational strategies that may overcome these risks. Hormonal contraception, including the use of oral contraceptives (OCs), is widely used in many women with epilepsy – there is no strong evidence of seizures worsening with their use. AEDs are the mainstay for seizure control in women with epilepsy. However, there are many factors to consider in the choice of AED therapy and hormonal contraception, since some AEDs can reduce the efficacy of OCs owing to pharmacokinetic interactions. Estrogens and progestogens are metabolized by cytochrome P450 3A4. AEDs, such as phenytoin, phenobarbital, carbamazepine, felbamate, topiramate, oxcarbazepine and primidone, induce cytochrome P450 3A4, leading to enhanced metabolism of either or both the estrogenic and progestogenic component of OCs, thereby reducing their efficacy in preventing pregnancy. OCs can also decrease the concentrations of AEDs such as lamotrigine and, thereby, increase the risk of seizures. Increased awareness of AED interactions may help optimize seizure therapy in women with epilepsy.     

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.

     

Problems in therapeutic drug monitoring: free drug level monitoring

Historically, it has been assumed that only free drug concentration is the pharmacologically active species. This article reviews the theoretical pharmacological and pharmacokinetic justifications for monitoring free drug levels. The determinants likely to influence plasma protein binding and the free concentrations of drugs are delineated. The different methods which can be used for determining free drug level are presented. Their advantages and drawbacks as well as their reliability and suitability for routine clinical practice are discussed. Currently, antiepileptic drugs such as valproic acid, phenytoin, carbamazepine and a few antiarrhythmic drugs meet the theoretical criteria justifying free drug level monitoring. Conditions causing alteration in free concentrations of these drugs are reported. But, for all these drugs, there is a considerable lack of data establishing the correlations between therapeutic or toxic response and free concentration. Presently, our capability to interpret correctly the free drug level data is still limited. In the future, much more effort must be devoted in order to provide sufficient information on the clinical relevance of free drug concentration.     

Short term impact of guidelines on vancomycin dosing and therapeutic drug monitoring

Background After medical center implementation of 2009 ASHP/IDSA guidelines, we evaluated the appropriateness of vancomycin dosing and TDM. Objective Our primary objectives were to assess short term effects on (1) appropriateness of initial vancomycin dosing, (2) appropriateness of sampling of plasma levels, before and after implementation of guidelines. Method The study was conducted in two phases, pre-guideline and post-guideline implementation. The interventions included (1) Nurses and phlebotomist education regarding the appropriate timing of vancomycin sampling, (2) A nomogram for appropriate initial dosing that was distributed to medical staff. Patient demographics, dosing and timing of sampling were collected in eligible patients and assessed for appropriateness. Results The appropriateness of the prescribed dose increased from 51% (128/253) of patients during the pre period to 78% (155/200) (p?<?0.0001) during the post period. Similarly, overall appropriateness of sampling of vancomycin troughs at steady state improved from 36% (63/173) pre to 55% (106/191) (p?<?0.03) post. Specifically, the appropriate timing of troughs (within 30?min of the next dose) increased from 37% (64/173) during the pre period to 78% (149/191) during the post period (p?<?0.0001). Conclusion Adoption of the guidelines with associated training resulted in significant short term improvement in vancomycin dosing and TDM