三种抗结核药物血药浓度调控成功率的比较分析

目的 基于治疗药物监测(TDM),分析抗结核药物异烟肼(INH)、利福平(RFP)、吡嗪酰胺(PZA)的血药浓度调控结果。方法 利用西安市胸科医院信息管理系统,收集2016年11月至2017年11月期间,根据临床治疗的需要,进行剂量调整及有实施前后2次及以上血浆药物浓度监测资料的初治确诊肺结核患者作为研究对象,共132例。其中,INH、RFP和PZA等3种一线抗结核药物实施2次及以上TDM监测患者例数及剂量调整患者例数为:INH组符合上述两种情况的患者分别为50例和19例;RFP组分别为47例和9例;PZA组分别为35例和11例。分析各组患者药物剂量调整情况。结果 INH、RFP和PZA组血药浓度调整率分别为38.0%(19/50)、19.1%(9/47)和31.4%(11/35)。INH组血药浓度调控成功率为31.6%(6/19);RFP组血药浓度调控成功率为7/9;PZA组血药浓度调控成功率为81.8%(9/11);三组比较差异有统计学意义(Fisher精确概率法,P=0.013),INH组血药浓度调控成功率明显低于PZA组和RFP组。结论 三种一线抗结核药物血药浓度在一次剂量调整后都不能完全达到治疗浓度范围内,其中INH与RFP和PZA相比,其剂量调整的成功率较低,这提示基于TDM制定给药剂量的方案还不能够实现一步到位,针对具体患者和药物品种还有进一步加强TDM和剂量调整。     

抗结核药治疗药物监测临床应用专家共识

治疗药物监测(therapeutic drug monitoring,TDM)是通过测定患者体内的药物暴露、药理标志物或药效指标,利用定量药理模型,以药物治疗窗为基准,指导制订适合患者的个体化给药方案。抗结核治疗过程中,存在药物浓度个体差异大、不良反应多等问题,可能导致治疗失败、耐药和复发。进行抗结核药物TDM,可以优化药物治疗方案,提高药物疗效,降低不良反应。为推进中国结核病TDM规范化,保证TDM的科学性、伦理性、合法性,使患者最大程度获益,经有关结核病临床和基础研究领域的专家反复讨论,就抗结核药物TDM的意义、适应证、检测方法、实施流程及TDM的质量控制等,制订了《抗结核药治疗药物监测临床应用专家共识》。     

肺部真菌感染患者伏立康唑血药浓度监测的临床应用

目的 通过监测肺部真菌感染患者伏立康唑的血药浓度,探讨伏立康唑血药浓度与临床疗效和不良反应的相关性以及在不同病区的特点.方法 采用高效液相色谱法一荧光法测定伏立康唑血药浓度,观察不同病区肺部真菌感染患者在治疗期间的临床疗效和不良反应发生的情况.结果 共纳入87例患者,伏立康唑血药浓度检测次数为133次,87例患者首次检测的血药浓度为(3.37±2.6) mg/L,133次检测的血药浓度为(2.98±2.28) mg/L;静脉治疗时血药浓度(3.30±2.61) mg/L,口服治疗时血药浓度为(2.31±2.02) mg/L,静脉治疗的血药浓度显著高于口服治疗的血药浓度(P=0.018);门诊患者血药浓度为(3.06±2.2) mg/L,普通病区患者血药浓度为(2.6±2.5) mg/L,ICU患者血药浓度为(3.1±2.5)mg/L,三组间差异无统计学意义,但对于同一患者而言,门诊患者药物浓度波动幅度较小,ICU患者血药浓度波动幅度较大.87例患者中,68例治疗成功(78％),19例治疗失败(22％),比较治疗成功组和失败组伏立康唑血药浓度,两组差异无统计学意义,提示血药浓度与疗效无明显相关性,但在治疗失败组中,血药浓度低于1 mg/L的比例明显高于治疗成功组,两组差异有统计学意义(36.8％ vs 14.7％,P=0.048).87例患者中,低钾血症发生率为32％,肝功能受损为14％,肾功能受损为3.4％,皮疹为3.4％,视觉障碍为2％.其中,视觉障碍和肝功能受损发生率与血药浓度有关系(均P＜0.05).结论 伏立康唑血药浓度波动范围大,平均血药浓度为(3.37±2.6) mg/L.血药浓度与临床疗效无明显相关性,但血药浓度低于1 mg/L,治疗失败率可能增加;神经系统的不良反应和肝功能受损与较高的血药浓度有关;建议治疗期间血药浓度维持在(1～5) mg/L.在使用伏立康唑时,不同来源的患者应监测其血药浓度,尤其是ICU患者,应加强血药浓度的监测,及时调整用药方案,以减少药物不良反应.     

洛汀新对2型糖尿病伴高血压者ET、NO的研究

洛汀新目前较为一致地在糖尿病（DM）伴高血压（HT）者中，作为临床抗高血压的一线用药。本文试图应用ACEI药物对2TDM伴与不伴高血压（HT）者的内皮素（ET）、一氧化氮（NO）水平的观察，认识该药物作用机理。     

氨茶碱血药浓度测定的临床应用

我院对83例支气管哮喘及慢性喘息型支气管炎患者服用氨茶碱及长效茶碱片后进行血清茶碱药物测定,观察药物剂量、血药浓度及疗效之间的关系,并探讨通过血药浓度测定如何指导临床用药个体化。     

利奈唑胺血清药物浓度监测在耐药结核病患者中的应用

利奈唑胺是一种新型的?唑烷酮类抗生素,是治疗耐药结核病的关键药物,该药治疗窗口狭窄,虽然疗效明显,但是临床应用不良反应的发生率高,如何安全有效地应用该药治疗耐药结核病一直困扰临床医生。治疗药物监测（therapeuticdrugmonitoring,TDM）通过监测患者血液中的药物浓度,可为药物剂量调整提供依据,使药物达到有效治疗浓度的同时最大程度地降低不良反应发生。目前国内外均有报道利用TDM研究利奈唑胺在耐药结核病患者中的最佳使用剂量和疗程,探讨利奈唑胺的谷浓度、峰浓度与不良反应发生率之间的关系,特别是对老年人、儿童、肝肾功能不全的患者临床安全使用利奈唑胺个体化治疗进行系列的探索研究。本文对利奈唑胺不良反应的发生机制、利奈唑胺的使用剂量及安全性、利奈唑胺药物浓度的影响因素、TDM的方式和应用等进行综述,为更加安全有效地应用利奈唑胺治疗耐药结核病提供参考。     

治疗性药物监测在结核病治疗中的应用进展

治疗性药物监测(therapeutic drug monitoring,TDM)是应用血液、尿液或唾液中的药品浓度确定药品剂量,为患者制定治疗方案,以获得最佳疗效,减少耐药及不良反应的检测技术。TDM是个体化治疗的重要策略,可为临床调整药品剂量提供参考。结核病患者血药浓度个体差异大、不良反应多,常导致治疗失败、复发和耐药。目前在结核病治疗中TDM尚未实现标准化,也无任何官方指南。但最近国外的指南推荐对有药品暴露改变风险或预后不良的结核病患者,在治疗期间应行TDM。因此,作者分别就TDM的定义及临床意义、检测技术方法、抗结核药品治疗应用情况作一综述,为临床医师提供参考。     

70例儿童癫痫患者卡马西平血药浓度监测结果分析

目的评价儿童癫痫患者卡马西平(CBZ)的临床合理应用情况。方法回顾分析儿童癫痫患者70例CBZ血药浓度监测结果。结果不同CBZ血药浓度对临床疗效的影响不同,差异有统计学意义(P0.05);单用CBZ和CBZ与常用抗癫痫药(AEDs)联合用药对临床疗效的影响差异无统计学意义(P0.05);不同年龄及给药剂量对CBZ血药浓度的影响差异有统计学意义(P0.05),不同性别与是否联合用药对CBZ血药浓度的影响差异无统计学意义(P0.05)。结论 CBZ血药浓度个体差异很大,应通过对其进行监测,并结合临床疗效制定个体化给药方案。     

胃癌瘤体注射卡铂血药浓度与临床相关性研究

我们曾选择进展期胃癌为对象，把卡铂（ｃａｒｂｏ－ｐｌａｔｉｎ）直接注入瘤体内，取得较好疗效［１］。在此基础上，我们应用高效液相色谱法测定血药浓度，进一步研究卡铂的血药浓度与临床疗效及毒副作用的相关性，为局部应用化疗药物提供实验依据。１．病例选择：１９...     

血药浓度与合理用药

血药浓度是指血液中的药物浓度。药物在血液中有的以游离状态存在,有的溶解在血浆中向其他组织转运,有的可与血浆蛋白结合或进入血球中。药代动力学研究表明:许多药物的疗效和毒性与血药浓度相关。研究血药浓度对指导临床安全、合理     

Updates in therapeutic drug monitoring in inflammatory bowel disease

Biologics and immunomodulators (IMM) are generally considered the most effective therapies for the treatment of ulcerative colitis and Crohn’s disease. However, despite the efficacy of these therapies, many patients either have a primary lack of response or a secondary loss of response to these medications. Therapeutic drug monitoring (TDM) is a systematic approach to managing such patients. In this review, we summarize the latest data on TDM, including reactive and proactive TDM, in patients with inflammatory bowel disease on biologics and/or IMM.     

What's in a trough? Therapeutic drug monitoring and antiretroviral regimens

The benefits and toxicity of any drug are a function of the drug's concentration in the patient. Therapeutic drug monitoring (TDM), or drug concentration analysis, implies that a patient's drug concentration must fall within a certain range in order for the drug to be therapeutic. TDM requirements are described in a table. Researchers are looking at the relationship between antiretroviral drug concentrations and clinical outcome. There is no consensus regarding TDM use for antiretroviral drugs. An appendix includes text from the AIDS Clinical Trials Group Pharmacology Committee Position Paper on Therapeutic Drug Monitoring for Antiretroviral Drugs. The committee does not recommend using drug concentrations to change antiretroviral therapy in individual patients.     

Use of therapeutic drug monitoring for multidrug-resistant tuberculosis patients

STUDY OBJECTIVES: Therapeutic drug monitoring (TDM) is the process of obtaining the serum concentration of a medication and modifying the dose based on the results. Little is known about the application of TDM in the treatment of patients with multidrug-resistant (MDR) tuberculosis (TB) in clinical practice. This study characterized how TDM was applied in the management of MDR TB patients, and examined the clinical indications for ordering TDM, the process for obtaining drug concentrations, and the clinician response to the drug concentrations. DESIGN: In a retrospective study, we compared the clinical and demographic characteristics of MDR TB patients who received TDM with those who did not. The clinical application of TDM also was described in patients who received TDM. SETTING: A municipal TB control program.Patients or participants: Patients in whom TB was diagnosed that was caused by an isolate resistant to at least isoniazid and rifampin, and who received treatment for TB in one of the health department chest clinics between July 1, 1993, and August 31, 1997, were studied. RESULTS: Forty-nine patients receiving TDM had a longer time to culture conversion and treatment duration, more pulmonary TB in combination with an extrapulmonary site, drug resistance, and visits to the health department clinics (p < 0.05) than the 60 patients without TDM. Of the 49 patients who had initial TDM, 73.5% of them had the reason for being tested specified. A total of 85.7% of initial TDM results were collected at the appropriate time of blood sampling. Clinician response to TDM results varied with the drug that was being tested. CONCLUSIONS: The use of TDM depended largely on the patient's clinical presentation. Site-specific guidelines on the use of TDM for managing TB patients may maximize the benefit of TDM.     

Optimizing antifungal drug dosing and monitoring to avoid toxicity and improve outcomes in patients with haematological disorders

Antifungal prophylaxis, empirical therapy and treatment of established fungal infections in the haematology population may be associated with significant toxicity or drug interactions leading to sub-therapeutic antifungal drug concentrations and poorer clinical outcomes. These risks may be minimised by clinical assessment, laboratory monitoring of biochemical or haematological indices, avoidance of particular drug combinations and dose modification in certain circumstances. Specific measures, such as the optimal timing of oral drug administration in relation to meals, use of pre-hydration and electrolyte supplementation may also be required. For certain agents, therapeutic drug monitoring (TDM) is warranted where non-compliance, non-linear pharmacokinetics, a narrow therapeutic window, suspected drug interaction or unexpected toxicity are encountered. Pharmacokinetics and pharmacodynamics of clinical relevance to the haematology population are discussed for the azole, polyene and echinocandin classes of antifungal agents. The evidence supporting an association between TDM and enhanced treatment outcomes is presented for individual antifungal drugs, and recommendations for clinical practice are provided. Further randomised study of newer antifungal agents, such as posaconazole, is required to explore the potential for improved clinical outcomes in association with TDM.     

Pharmacodynamics and clinical use of anti-HIV drugs

Antiretroviral drug exposure has been linked to both antiviral efficacy and the development of toxicity and further research in this area is ongoing and necessary. Use of these data may have important implications for TDM of HAART regimens in clinical practice. TDM, in conjunction with an assessment of the patient's viral resistance in the form of an IQ, needs to be examined and validated in large clinical trials.     

中国成人肝移植受体微乳化环孢素A吸收期血药浓度与药物暴露量的相关性研究

目的通过分析中国成人肝移植受体微乳化环孢素A(cyclosporine microemulsion，Neoral)吸收期不同采样点血药浓度与药物暴露量的相关性，探讨用服药后2h浓度(C2)代替吸收期药物暴露量(AUC0-4)进行治疗药物监测的可能性。方法通过定期测定22例中国成人肝移植受体口服Neoral前及服药后1、2、3、4h的血药浓度，用直线回归分析计算不同采样点与AUC0的相关系数。结果服药后2h浓度(C2)与AUC0-4的相关性最高，相关系数r=0.96，谷浓度(C0)与AUC0-4的相关性最差，r=0．67,并且C2与AUC0-4相关性的稳定性最好，随访期间r^2一直维持在0．91以上。结论 C2与Neoral吸收期药物暴露量的相关性最高，并且这种相关性的稳定性最好。可以考虑使用C2作为单一采样点代替AUC0-4进行Neoral治疗药物监测。