7种药物有效血药浓度参考范围的探讨

目的:探讨7种药物的有效血药浓度参考范围。方法:通过咨询已经开展治疗药物监测(TDM)医院的工作人员,查询药品说明书,出版的书籍及检索相关文献,分析能够达到药物治疗目的的最低有效浓度和出现中毒反应的最小中毒浓度,作为临床TDM值的参考范围。结果:初步确定了万古霉素、卡马西平、丙戊酸钠、地高辛、环孢素、他克莫司和吗替麦考酚酯TDM监测指标及其参考范围。结论:药物TDM监测指标参考值可以为临床药师提供参考,给临床医师个体化用药提供了药物调整剂量的依据,确保药物疗效。     

中国新生儿万古霉素血药浓度监测回顾性分析

目的:分析中国新生儿万古霉素治疗药物浓度监测(TDM)现状,为临床用药提供建议。方法:检索中文数据库中国知网、万方数据、维普网,检索时限为建库至2017年12月31日,纳入新生儿万古霉素TDM文献,统计监测例次、监测依据、监测方法、给药方案、首次采血时间、谷浓度范围、不良反应。结果:纳入14篇文献,1273例新生儿的万古霉素TDM 1968例次。多数文献明确了以指南或专家共识作为监测依据,测定方法以高效液相色谱法为主(71.80%),92.38%的TDM采用了说明书的给药方案,73.68%的TDM采用4~5个维持剂量采血;21.24%的TDM谷浓度平均值在10~20 mg/L之间,78.76%的TDM谷浓度平均值<10 mg/L,不良反应发生率为15.24%。结论:中国新生儿万古霉素TDM数量较少,且60%以上的谷浓度监测结果不在治疗范围内,加强TDM十分必要。     

375例次药物浓度监测分析

目的:统计分析375例次药物浓度测定结果及监测目的,探讨治疗药物监测(TDM)的临床应用价值。方法:回顾性调查中山市人民医院2002年8月～2003年8月进行的TDM共375例次(302人次),统计患者基本情况,以及TDM的目的和结果。结果:375例次TDM中,监测目的用于判断是否中毒的13例次,判断是否曾经用药的55例次,判断疗效及调整剂量的286例次,去除毒物过程监测的21例次。未达有效浓度范围的158例次(42.1%),高于有效浓度范围的72例次(19.2%)。地高辛高于有效浓度例次最多。结论:TDM不仅能监测药物疗效、调整药物剂量,而且能帮助临床诊断和治疗方面发挥一定的指导作用。     

我院2011-2012年164例次地高辛血药监测浓度回顾性分析

目的:监测地高辛血药浓度,为临床安全、有效、合理使用地高辛提供参考依据。方法:采用均相酶扩大免疫分析法,对2011-2012年我院164例次地高辛血药浓度进行监测。回顾性分析年龄、性别、病理状态、服药剂量、频次以及联合用药对地高辛血药浓度的影响。结果:监测数据在一般参考治疗浓度范围内占59.1%,平均血药浓度为(1.22±0.42)ng/ml,达到中毒浓度者占32.9%。年龄的增长、肾功能的减退、日剂量增加均可升高地高辛血药浓度,女性患者的血药浓度比男性患者略高,合并用药与地高辛血药浓度也有一定的相关性。结论:地高辛血药浓度的个体差异性较大,应结合患者生理病理、用药情况、血药浓度监测数据,综合评估地高辛药物浓度与其临床疗效的关系,制订个体化的给药方案,切实保证临床用药的合理性、安全性、有效性。     

儿童地高辛血药浓度监测及影响因素分析

目的:观察地高辛血药浓度监测对患儿个体化用药的作用.方法:应用化学发光免疫法(CLIA)测定地高辛血药浓度,并对结果进行分析.结果:161例患儿中在有效血药浓度范围内(0.8～2.0 ng/mL)为79例(占49.1%),小于0.8 ng/mL 74例(占46.0%),大于2.0 ng/mL 8例(占4.9%).结论:应从患儿个体的药效学、药动学出发,结合血药浓度监测及临床观察,在注重防止地高辛中毒反应的同时,使患儿的治疗达到有效、合理、安全.     

儿童地高辛的血药浓度监测及影响因素分析

目的 分析影响地高辛血药浓度的可能因素,保证临床患儿的用药安全。方法 回顾性分析某院2019年7月～2021年2月期间收治的心脏功能异常、接受地高辛治疗的60例患儿的临床资料,整理并罗列患儿基本信息、用药情况等,运用化学发光微粒子免疫分析法（CMIA）检测患儿地高辛血清浓度,分析其可能影响血药浓度变化的相关因素。结果 60例患儿中合理使用地高辛剂量符合有效血药浓度范围（0.8～2.0 ng/ml）的29例,占比48.33%;27例浓度小于0.8 ng/ml,占比45.00%;有4例超过2.0 ng/ml,占比3.33%,这其中有2例中毒患儿,占比50.0%。证实地高辛浓度与患儿年龄和体重、联合用药、疾病种类与给药方式等密切相关。结论 应从患儿个体的药效学、药动学为出发点,指导患儿地高辛的个体化药物治疗,有效防治药物中毒反应,促进患儿治疗安全、合理、有效。     

婴儿口服地高辛醑剂后血药浓度监测结果分析

目的 探讨婴儿口服地高辛醑剂后血药浓度与临床疗效、给药剂量、合并用药情况、性别、年龄和体重的相关性.方法 查阅广东省人民医院2005 ～2009年口服地高辛醑剂的婴儿病历,记录疗效、用药情况、性别、体重、年龄、血药浓度监测结果等,用统计软件SPSS 13.0进行分析.结果 415例婴儿口服地高辛醑剂血药浓度测定值在治疗浓度0.8～2.2 ng/ml的共270例,占65.1％;低于治疗浓度范围下限(＜0.8 ng/ml)的共107例,占25.8％;高于治疗浓度范围上限(＞2.2 ng/ml)的共48例,占11.6％.婴儿地高辛血药浓度值与性别不存在明显相关性,但与给药剂量、年龄、体重、合并用药和具体病情有关.结论 地高辛血药浓度受个体因素与具体病情影响,药物剂量的制订和调整,应考虑可能影响地高辛血药浓度的各种因素,结合婴儿自身情况来决定最佳给药方案.     

小儿地高辛血药浓度监测及影响因素分析

目的 探讨地高辛血药浓度监测结果与可能影响因素,为小儿地高辛的个体化用药提供参考。方法 回顾性分析2017年7月至2018年7月中国科学技术大学附属第一医院(安徽省立医院)因心脏功能异常等口服地高辛治疗的小儿病例资料56例,收集并筛选小儿个体信息、用药信息等,采用化学发光微粒子免疫分析法(CMIA)测定小儿地高辛血清浓度,通过多元线性回归方法分析影响血药浓度变化的可能因素。结果 小儿使用地高辛的临床给药剂量为(9.35±4.28)μg·kg-1·d-1,小儿地高辛血药浓度处于有效浓度(0.5~2.0 ng/mL)为46例,占82.14%;大于2.0 ng/mL为3例,占5.36%;小于0.5 ng/mL为7例,占12.5%。地高辛的血药浓度变化与性别因素无相关性(P＞0.05),与年龄和体质量因素呈负相关(r＝0.182;r＝0.105,P＜0.01),与疾病种类、联合用药和地高辛用量呈正相关(r＝0.098;r＝0.243;r＝0.196,P＜0.01),因抽血时间基本一致,暂未纳入血药浓度影响因素分析范围。结论 小儿地高辛的个体化药学指导应从小儿个体的药效学、药动学出发,结合血药浓度监测及临床观察,在注重防止地高辛中毒反应的同时,促进小儿的治疗安全、有效、合理。     

维吾尔族肾病综合征患儿他克莫司全血谷浓度监测分析

目的监测维吾尔族原发性肾病综合征(PNS)患儿他克莫司全血谷浓度并分析相关临床数据,以期为维吾尔族PNS患儿个体化应用他克莫司提供依据。方法对接受他克莫司治疗的70例维吾尔族PNS患儿的血药浓度、生化检验指标及合并用药进行回顾性调查分析,探讨他克莫司全血谷浓度与临床疗效的相关性,根据临床疗效分为完全缓解组(CR组)、部分缓解组(PR组)、未缓解组(NR组)。结果CR组剂量标准化谷浓度为(2.95±1.17)ng/mL/[mg/(kg·d)]、PR组剂量标准化谷浓度为(4.22±2.92)ng/mL/[mg/(kg·d)]、NR组剂量标准化谷浓度为(1.72±1.43)ng/mL/[mg/(kg·d)],三组比较差异有统计学意义(P<0.05),但三组给药剂量差异无统计学意义(P>0.05)。他克莫司治疗维吾尔族PNS患儿的缓解率为75.71%。结论他克莫司全血谷浓度与药物剂量及相关药物代谢基因相关,在全血谷浓度达5~10 ng/mL时,可达到满意的治疗效果。     

945例次血药浓度监测结果分析

目的对我院治疗药物浓度监测数据进行分析,为临床合理用药提供参考。方法采用系统回顾性方法,对我院2003年11月～2006年5月期间292例患者945次血药浓度结果进行分析。结果血药浓度治疗窗内:卡马西平最高(80.6%),地高辛最低(27.5%);剂量不足:地高辛最高(61.2%),中毒剂量:地高辛最高(11.3%);除环孢素外,1例患者测定一次血药浓度的比例均高于60%;癫痫类药物:罕见1位患者测定次数多于3次;环孢素:1例患者监测次数大于5次的为51.9%。结论TDM在我院开展,多种原因导致药物未在治疗窗内,监测次数偏少。临床药师和医师应联合,充分利用TDM技术,建立一个长期有效的治疗方案,最大限度保障患者用药安全、有效、经济、合理。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.