某三级甲等医院住院患者万古霉素血药浓度监测结果与疗效关系分析

目的：了解万古霉素血药浓度监测的临床应用情况,以指导临床合理用药。方法：对某三级甲等医院2010年9月—2012年9月使用万古霉素住院患者进行的118例次血药浓度监测结果进行回顾性分析。结果：该院住院患者使用万古霉素的总有效率为70.21%（33/47）;118次万古霉素血药浓度监测所得谷浓度在治疗窗范围内的仅占30.6%（19/62）;谷浓度低于10 mg/L的占69.4%（43/62）;谷浓度〉10 mg/L的患者肾毒性发生率为8.5%（4/47）。结论：该院住院患者万古霉素用量和血药浓度均偏低,需重视其血药浓度监测并结合临床实际,实现个体化给药。     

万古霉素治疗新生儿败血症血药浓度监测及应用分析

目的 探讨万古霉素治疗新生儿败血症的临床应用效果,为临床治疗提供参考.方法 选取2013年1月至2015年1月使用万古霉素治疗新生儿败血症患儿68例,应用高效液相色谱法(HPLC)测定患儿应用万古霉素后的血药峰浓度和谷浓度,并根据其结果进行疗效分析.结果 68例患儿中,测得万古霉素血药浓度的谷浓度最低值为2.15mg/L,最高值为13.65 mg/L,甲均为(6.24±2.05) mg/L,峰浓度最低值为8.96 mg/L,最高值为52.06mg/L,平均为(31.48±11.12) mg/L,治疗效果显著.结论 严格掌握万古霉素的使用剂量,实时监测其血药浓度,做到个体化给药,可以有效治疗新生儿败血症,减少不良反应的发生.     

我院万古霉素临床合理使用评价及血药浓度监测分析

目的:为万古霉素临床合理使用提供参考。方法:收集我院2015年1月-2016年6月使用万古霉素的299例患者的病历资料,对用药情况、用药合理性、病原学检查结果、万古霉素血药浓度、疗效、不良反应等指标进行统计分析。结果:我院住院患者应用万古霉素多为治疗用药,且以经验性治疗用药为主(90.30%);用药前样本送检率为61.82%,有52例(28.42%)患者检出特异病原菌。万古霉素用药不合理的有69例(23.08%),均为药物浓度不适宜。万古霉素血药浓度监测率为43.33%,谷浓度维持在10~20mg/L的占40.00%;治疗有效率为79.39%;治疗后急性肾损伤的发生率为5.41%。结论:我院住院患者应用万古霉素前样本送检率和血药浓度监测率均偏低,有效血药谷浓度的患者比例亦低。医院应加强万古霉素的应用管理,促进临床个体化用药。     

临床药师参与重症监护室新生儿万古霉素个体化治疗实践

目的:分析临床药师参与75例重症监护室新生儿万古霉素个体化治疗实践,为新生儿特别是早产儿万古霉素安全合理应用提供参考.方法:收集我院2018年4月至2019年12月临床药师参与万古霉素治疗的75例重症监护新生患儿的临床资料,包括基本信息、疾病分布、病原学检查、万古霉素使用情况、血药浓度、治疗转归及药品不良反应等,进行统计分析.结果:75例重症监护室患儿中,64例(85.33％)为早产儿,疾病分布以败血症最多(55例,73.33％),抗菌药物使用前病原送检率100％,阳性检出率为52.00％ (39/75).首次万古霉素治疗方案医师对药师建议的采纳度为72.00％ (54/75),首次谷浓度在5～15 μg/mL的患儿占74.67％ (56/75),治疗总有效率为70.67％(53/75).临床药师开展药学监护,有1例患儿用药后出现肝功能损伤,其余患儿无不良反应发生.结论:临床药师参与新生儿万古霉素个体化治疗,监测万古霉素血药浓度,有助于提高新生患儿感染治疗有效率,确保临床用药安全.     

新生儿的万古霉素血药浓度监测及安全性评价

目的:建立以高效液相色谱(HPLC)法测定万古霉素血药浓度的方法,探讨万古霉素在新生儿的血药浓度与临床疗效、不良反应之间的关系。方法:采用Hypersil-ODS柱,流动相为乙腈-磷酸二氢钾(0.05mol.L-1,pH3.21)(10∶90),检测波长为236nm,流速为1.00mL.min-1;新生儿重症感染病例30例,用万古霉素治疗7～14d,给药剂量按每次10～15mg.kg-1,观察给药前后患儿肝、肾功能指标(ALT、AST、T-Bil、D-Bil、BUN、CCr)及不良反应情况;监测患儿万古霉素的峰(坪)浓度和谷浓度。结果:30例患儿治疗中未见明显不良反应,万古霉素的谷浓度的平均值为(5.8±3.4)mg.L-1,峰(坪)浓度的平均值为(30.9±12.0)mg.L-1,给药前后肝、肾功能指标比较差异无显著性。结论:万古霉素对治疗新生儿重症感染疗效确切,临床应用时必须严格掌握适应症、剂量,在血药浓度的监测下个体化治疗。     

39例新生儿万古霉素血药浓度监测与用药分析

目的:评价万古霉素在新生儿的临床应用及其血药浓度监测情况,为临床合理用药提供参考。方法:采用回顾性分析方法,收集2012-2013年在新生儿使用万古霉素治疗并进行血药浓度监测的39例,对其疾病分布、病原学检查、PCT检测、药物敏感试验、用药天数、药物疗效、合并用药、肝肾功能等指标进行统计分析。结果:39例患儿中临床第一诊断为新生儿肺炎者比例最高,为29例(74.36%);病原学送检率100%,阳性检出率69.2%;药物敏感试验显示对万古霉素高度敏感的占77.78%;PCT送检率97.44%;万古霉素血药谷浓度范围在15~20 μg·ml^-1的为19.05%;平均用药时间(12.4±4.9)d;联合应用2种抗菌药物的比例为84.62%;抽样患儿使用万古霉素治疗的有效率为89.7%。结论:新生儿使用万古霉素治疗由革兰阳性菌引起的重症感染疗效确切,但应进行血药浓度(谷浓度)监测,使其血药浓度维持在安全有效范围内,以提高用药的安全性和有效性。     

新生儿万古霉素血药浓度监测与不良反应分析

目的:探讨新生儿应用万古霉素行血药浓度监测的意义。方法:选取2012年1月至2014年11月使用万古霉素治疗的住院新生儿174例,采用高效液相色谱(HPLC)法测定患儿万古霉素血药峰浓度和谷浓度,并观察患儿不良反应发生情况。结果:174例患儿中,万古霉素血药谷浓度最低值为2.04 mg·L-1,最高值为13.49 mg·L-1,平均为(6.01±2.18)mg·L-1,峰浓度最低值为9.04 mg·L-1,最高值为50.47 mg·L-1,平均为(32.17±11.08)mg·L-1;有101例患儿血清谷浓度<5 mg·L-1,治疗总有效率为93.07%,不良反应率为16.83%,45例患儿血清谷浓度在5~10 mg·L-1,治疗总有效率为100.00%,不良反应率为16.83%,28例患儿血清谷浓度>10 mg·L-1,治疗总有效率为100.00%,不良反应率为28.57%,3个不同范围血药浓度的治疗疗效和不良反应比较,差异无统计学意义(P>0.05);不良反应主要以肝损害和听力损害为主,其中肝损害发生率为9.20%,听力损害发生率为10.34%;随着万古霉素血清谷浓度增加,不良反应发生率没有趋势性增加(X2=2.032,P=0.154)。结论:新生儿应用万古霉素有较高的肝损害和听力损害发生率,临床应用应严格掌握剂量、适应证,在血药浓度监测下行个体化治疗。     

我院41例万古霉素血药浓度监测与临床用药分析

目的:评价我院万古霉素血药浓度监测及其临床应用情况。方法:采用回顾性调查方法,对我院2005年11月～2008年12月应用万古霉素并监测血药浓度的41例住院患者的临床资料(基础疾病、细菌学培养结果、万古霉素血药浓度值、疗效、肾功能情况等)进行统计、分析。结果:我院住院患者应用万古霉素的总有效率为65.0%;万古霉素血药浓度所测得峰值<25mg.L-1者占62.7%,谷值<5mg.L-1者占55.2%;治疗后肾功能异常发生率为12.2%。结论:我院住院患者万古霉素应用量和血药浓度均偏低,需重视其血药浓度监测并结合临床实际,实现个体化给药。     

123例万古霉素血药浓度监测及临床用药分析

目的 通过分析123例患者万古霉素血药浓度的监测结果,为临床合理用药提供参考.方法 采用回顾性调查方法,对本院2010年1 月～2011 年1 月应用万古霉素并监测血药浓度的123 例住院患者的临床资料(基础疾病、细菌学培养结果 、万古霉素血药浓度值、疗效、肾功能情况等)进行统计、分析.结果 本院住院患者应用万古霉素的总有效率为69.11%;万古霉素血药浓度所测得峰值＜ 30 μg/mL者占60.18%,＜ 10 μg/mL者占13.85%;治疗后肾功能异常发生率为12.20%.结论 本院住院患者万古霉素应用量和血药浓度均偏低,需重视其血药浓度监测并结合临床实际,实现个体化给药.     

高肌酐清除率重症患者万古霉素血药浓度监测分析

目的：通过分析我院高肌酐清除率重症患者万古霉素血清谷浓度变化,探讨该类患者最优化的万古霉素给药方案。方法：采用回顾性分析研究,选择2016年3月至2016年12月入住我院重症监护室使用并监测万古霉素血清谷浓度的重症患者,对其中肌酐清除率大于120ml/min的患者的一般资料、万古霉素血清谷浓度、疗效等临床资料进行统计分析。结果：共纳入57例患者,共计96次万古霉素血清谷浓度,仅21.88%(21/96)达到目标浓度(15~20mg/L),其中低于15 mg/L者62.50%(60/96),高于20 mg/L者15.62%(15/96)。肌酐清除率相对偏低组(120~149 ml/min),谷浓度达标率及超标率均高于其他组,肌酐清除率＞240ml/min与Ccr120~149 ml/min万古霉素血清谷浓度差异有统计学意义(P＜0.05);多重线性回归分析显示,肌酐清除率、给药剂量及血浆白蛋白时影响万古霉素血清谷浓度的主要因素(P＜0.05),性别、年龄、SOFA评分、血肌酐、总胆红素对万古霉素血清谷浓度的影响无统计学意义(P＞0.05);万古霉素达标者与未达标者病死率比较差异无统计学意义(χ2=0.690,P=0.406)。结论：高肌酐清除率重症患者万古霉素血清谷浓度临床达标率低,需密切监测血药浓度,及时调整治疗方案;肌酐清除率、给药剂量及血浆白蛋白对万古霉素血清谷浓度影响较大,制定给药方案时需考虑这些因素。     

Role of glutathione in reduction of arsenate and of gamma-glutamyltranspeptidase in disposition of arsenite in rats

Arsenate (AsV), the environmentally prevalent form of arsenic, is converted sequentially in the body to arsenite (AsIII), monomethylarsonic acid (MMAsV), monomethylarsonous acid (MMAsIII), and dimethylarsinic acid (DMAsV) and some trimethylated metabolites. Although the biliary excretion of arsenic in rats is known to be glutathione (GSH)-dependent, involving transport of arsenic-GSH conjugates, the role of GSH in the reduction of AsV to the more toxic AsIII in vivo has not been defined. Therefore, we studied how the fate of AsV is influenced by buthionine sulfoximine (BSO), which depletes GSH in tissues. Control and BSO-treated rats were given AsV (50 micromol/kg, i.v.) and arsenic metabolites in bile, urine, blood and tissues were analysed by HPLC-HG-AFS. BSO increased retention of AsV in blood and tissues and decreased appearance of AsIII in blood, bile (by 96%) and urine (by 63%). The biliary excretion of MMAsIII was also nearly abolished, the appearance of MMAsIII and MMAsV in the blood was delayed and the renal concentrations of these monomethylated arsenicals were decreased by BSO. Interestingly, appearance of DMAsV in blood and urine remained unchanged and the concentrations of this metabolite in the kidneys and muscle were even increased in response to BSO. To test the role of gamma-glutamyltranspeptidase (GGT) in arsenic disposition, the effect of the of the GGT inhibitor acivicin was investigated in rats injected with AsIII (50 micromol/kg, i.v.). Acivicin lowered the hepatic and renal GGT activities and increased the biliary as well as urinary excretion of GSH, but failed to alter the disposition (i.e. blood and tissue concentrations, biliary and urinary excretion) of AsIII and its metabolites. In conclusion, shortage of GSH decreases not only the hepatobiliary transport of arsenic, but also reduction of AsV and the formation of monomethylated arsenic, while not hindering the production of dimethylated arsenic. While GSH plays an important role in the disposition and toxicity of arsenic, GGT, which hydrolyses GSH and GSH conjugates, apparently does not influence the fate of the GSH-reactive trivalent arsenicals in rats.     

微透析取样技术在中药体内分析中的应用研究进展

本文综述了微透析取样技术在中药体内分析中的应用,介绍微透析取样技术的原理、组成、探针类型、特点,重点阐述了微透析取样技术在测定脑、血液、皮肤等组织器官中中药有效成分浓度的应用实例。表明微透析取样技术在中药药效研究中具有广阔的前景。     

应用PASS系统分析我院2010年住院医嘱

目的:了解我院2010年住院患者的合理用药情况,探讨如何利用合理用药监测系统( PASS)提高合理用药水平.方法:利用PASS对我院2010年15 966例住院患者的1 184 997条用药医嘱进行监测,以黑色警示医嘱为依据,收集不合理用药信息,并对监测结果进行统计、分析.结果:不合理用药医嘱50 261条,发生率为4.24％.绝对禁止黑色医嘱5441条,主要为药物相互作用(66.54％)、注射液体外配伍(17.86％)、用法用量(15.46％)、儿童警告(1.14％).结论:应用PASS系统能有效监测医嘱中的不合理用药情况,有利于提高临床合理用药水平,但PASS系统尚存在局限性,有待进一步完善.     

Changes in levels of dependency and predictors of mortality in elderly people in institutional care in Dunedin

The 1983 study of dependency of subjects in institutional care in Dunedin was repeated two years later. A significant increase in levels of dependency in residential homes, particularly in the Religious and Welfare sector was found. In 1983 there were 29 high dependency residents and 73 medium dependency residents in residential homes. In 1985 these numbers had increased to 55 and 86 respectively. There was no change in the number of low dependency residents. In 1983, 6 high dependency residents had been admitted to residential home care in the year prior to the study. In 1985 the number of high dependency residents recently admitted had increased to 23. There had also been a significant increase in the dependency of patients in Religious and Welfare continuing care hospitals. Of the 933 subjects in institutional care in 1983 who were able to be followed, 354 (37.9%) died in the following 2 years. Mortality rate was higher for those in hospital care (48.1%) than for those in residential home care (29.6%). Mortality rates were higher in more dependent subjects and this was evident for each measure of dependency.     

应用PASS系统对我院2008年住院医嘱的分析

目的监测分析2008年我院住院患者用药情况。方法将PASS系统嵌入医生工作站、临床药学工作站等子系统,构建合理用药计算机网络系统,对住院医嘱进行及时监测,将监测结果向医生反馈,并对其进行统计、分析。结果2008年共监测医嘱3 620 241条,不合理医嘱908条,占0.02%。不合理医嘱中,配伍禁忌(381条)占41.96%,用法用量(381条)占41.96%,药物相互作用(108条)占11.89%,儿童用药(38条)占4.19%。经与医生沟通后,更改不合理医嘱856条,占94.27%。结论PASS系统可有效监测医嘱中的不合理用药,通过与医生交流,大大减少药物不良事件的发生,值得临床推广应用,也为临床药师开展工作带来了极大的便利。但PASS系统尚存在局限性,有待进一步完善。     

Role of desacetylation in the detoxification of cephalothin in renal cells in culture

The toxicity of three cephalosporin antibiotics to rabbit kidney cells in culture was compared to their known nephrotoxic potential in vivo (cephaloridine greater than cefazolin greater than cephalothin). While cephalothin is considered to be a relatively nonnephrotoxic cephalosporin when administered to many species including humans and rabbits, in several in vitro systems involving rabbit renal tissue, cephalothin was comparatively more toxic than anticipated based on in vivo data. Cephalothin is extensively desacetylated in rabbits to a less microbiologically active metabolite, desacetylcephalothin. When a microsomal S9 fraction from rabbit kidney was added to the in vitro assay in cultured rabbit renal cells, cephalothin was desacetylated and its toxicity to kidney cells was reduced. The addition of S9 in vitro provided a toxicity ranking of the cephalosporins that correlated with their known in vivo nephrotoxic potentials (cephaloridine greater than cefazolin greater than cephalothin). The in vitro detoxification of cephalothin by S9 was blocked by the coadministration of the esterase inhibitor, aminocarb. Desacetylcephalothin was relatively nontoxic to rabbit renal tissue in vitro. These results suggest that the desacetylation of cephalothin in vivo represents a previously unrecognized mechanism of detoxification of this cephalosporin antibiotic. Furthermore, this mechanism of detoxification may be applicable to other acetylated cephalosporins.     

2009年某院住院患者抗真菌药用药调查

目的:分析讨论某院抗真菌药使用的合理性,为临床安全有效地使用抗真菌药提供参考。方法:回顾性统计分析某院2009年住院患者抗真菌药用药信息。结果:2009年某院住院患者抗真菌药DDDs排名前3名分别为:氟康唑、制霉菌素和伊曲康唑;使用金额排名前3名分别为:氟康唑、米卡芬净及卡泊芬净;更换一种抗真菌药进行治疗的患者数为176人,在全部患者中占13.4%。结论:应进一步强化用药指征的意识,提高标本送检率,同时改善某些抗真菌用药不合理更换的现象,以避免耐药性发生,从而更好更长远地体现抗真菌药的治疗价值。     

Kinetics of in vitro metabolism of methoxyphenamine in rats

1. Methoxyphenamine (MP) was metabolized in vitro by rat liver preparations to O-desmethylmethoxyphenamine (O-desmethyl-MP), N-desmethylmethoxyphenamine (N-desmethyl-MP) and 5-hydroxymethoxyphenamine (5-hydroxy-MP). These metabolic pathways were inhibited by SKF 525-A and carbon monoxide, which indicates that these reactions were mediated at least partly by an NADPH-dependent cytochrome P-450 system. 2. Strain differences in the metabolism of this drug in vitro were observed in female Lewis and Dark Agouti (DA) rats, which are proposed models for human debrisoquine phenotypes. Methoxyphenamine O-demethylase and 5-hydroxylase activity in DA rats were lower than those in Lewis rats. 3. The metabolic transformation of methoxyphenamine in vitro to O-desmethyl-MP was inhibited competitively by debrisoquine and sparteine. This indicates that the cytochrome P-450 isoenzyme mediating the metabolism of MP to O-desmethyl-MP is similar to that mediating metabolism of debrisoquine and sparteine. However, no inhibition was observed with methenytoin.     

Comparison of in vitro cell models in predicting in vivo brain entry of drugs

Although several in vitro models have been reported to predict the ability of drug candidates to cross the blood-brain barrier, their real in vivo relevance has rarely been evaluated. The present study demonstrates the in vivo relevance of simple unidirectional permeability coefficient (P(app)) determined in three in vitro cell models (BBMEC, Caco-2 and MDCKII-MDR1) for nine model drugs (alprenolol, atenolol, metoprolol, pindolol, entacapone, tolcapone, baclofen, midazolam and ondansetron) by using dual probe microdialysis in the rat brain and blood as an in vivo measure. There was a clear correlation between the P(app) and the unbound brain/blood ratios determined by in vivo microdialysis (BBMEC r=0.99, Caco-2 r=0.91 and MDCKII-MDR1 r=0.85). Despite of the substantial differences in the absolute in vitro P(app) values and regardless of the method used (side-by-side vs. filter insert system), the capability of the in vitro models to rank order drugs was similar. By this approach, thus, the additional value offered by the true endothelial cell model (BBMEC) remains obscure. The present results also highlight the need of both in vitro as well as in vivo methods in characterization of blood-brain barrier passage of new drug candidates.