我院ICU脑干出血患者医院感染病原菌分布及耐药性分析

目的:为临床合理使用抗菌药物提供参考。方法:收集2014年1月-2015年12月我院重症医学科(ICU)283例脑干出血患者的病原学资料,回顾性分析其医院感染病原菌的分布特征及耐药情况。结果:283例患者中,确诊为医院感染的患者共205例,感染率为72.44%;共送检临床标本765份,以痰液(60.00%)、血液(14.38%)和胆汁(9.54%)等标本为主;共检出病原菌765株,包括以肺炎克雷伯菌为主的革兰氏阴性菌496株(64.84%),以金黄色葡萄球菌为主的革兰氏阳性菌238株(31.11%)和以白色假丝酵母菌为主的真菌31株(4.05%);共检出产超广谱β-内酰胺酶(ESBLs)肺炎克雷伯菌89株、产ESBLs大肠埃希菌23株、耐甲氧西林金黄色葡萄球菌87株。肺炎克雷伯菌、大肠埃希菌、铜绿假单胞菌和鲍曼不动杆菌对碳青霉烯类药物敏感(耐药率<5%);金黄色葡萄球菌、表皮葡萄球菌和产色葡萄球菌对常用抗菌药物的耐药率均较高,但对万古霉素敏感(耐药率均为0)。结论:我院ICU脑干出血患者医院感染的主要病原菌为革兰氏阴性菌,其耐药情况及产酶情况不容乐观;对主要病原菌敏感性较高的药物包括碳青霉烯类药物和万古霉素等。临床应加强监测病原菌的耐药特征,有针对性地选用抗菌药物。     

2011-2016年我院1775株血流感染病原菌构成及其耐药性分析

目的:为临床合理使用抗菌药物提供参考。方法:收集我院2011年1月-2016年12月住院患者的血培养阳性标本,回顾性分析我院血液感染(BSI)病原菌分布及耐药情况。结果:2011-2016年,我院住院患者共送检血培养标本26 034份,其中阳性标本1 775份,总阳性率为6.82%;主要来源于肿瘤、血液科(10.65%),神经外科(8.28%)和儿科(8.00%)。共检出病原菌1 775株,包括以大肠埃希菌、肺炎克雷伯菌为主的革兰氏阴性菌967株(54.48%),以凝固酶阴性葡萄球菌、金黄色葡萄球菌为主的革兰氏阳性菌649株(36.56%)和以白色念珠菌为主的真菌159株(8.96%)。大肠埃希菌和肺炎克雷伯菌对常用抗菌药物均存在不同程度的耐药性,但对哌拉西林钠他唑巴坦钠、亚胺培南、美罗培南较敏感;鲍曼不动杆菌对含酶抑制剂类、头孢菌素类、氨基糖苷类、喹诺酮类药物的耐药率均较高;铜绿假单胞菌对第三代头孢菌素类、氨基糖苷类、喹诺酮类药物较敏感。金黄色葡萄球菌对青霉素类、头孢菌素类、氨基糖苷类药物的耐药率较高;凝固酶阴性葡萄球菌对大部分常用抗菌药物的耐药率均超过40%;但两者对利奈唑胺、万古霉素敏感,耐药率均为0。共检出产超广谱β-内酰胺酶(ESBLs)大肠埃希菌205株(42.01%)、产ESBLs肺炎克雷伯菌64株(30.33%)、耐甲氧西林金黄色葡萄球菌31株(17.61%);未检出耐万古霉素肠球菌和耐万古霉素金黄色葡萄球菌。结论:我院BSI病原菌主要分布在肿瘤、血液科等科室,以肠杆菌科细菌、葡萄球菌为主,真菌也占一定比例,其耐药及产酶情况不容乐观。对主要病原菌较敏感的抗菌药物包括碳青霉烯类、利奈唑胺和万古霉素等。     

儿童重症监护病房肺炎患者病原菌分布及耐药性分析

目的探讨我院儿童重症监护病房(PICU)肺炎患者病原菌分布及耐药情况,为合理选用抗菌药物提供依据。方法对我院PICU 2012年1月-2013年12月肺炎患者痰培养标本中分离出的病原菌及耐药性进行回顾性分析。结果共培养分离出病原菌289株,其中革兰氏阴性菌194株,占67.13%,主要为大肠埃希菌、肺炎克雷伯菌、流感嗜血杆菌。革兰氏阴性菌对青霉素类及头孢菌素类的耐药率较高,未发现对碳青霉烯类抗生素耐药。培养出革兰氏阳性菌90株,占31.14%,主要为金黄色葡萄球菌、肺炎链球菌;革兰氏阳性球菌对青霉素类、头孢类及大环内酯类耐药率较高,未发现对万古霉素耐药。培养出真菌5株,占1.73%。结论我院PICU肺炎患者优势病原菌为革兰阴性杆菌,以大肠埃希菌、肺炎克雷伯菌和流感嗜血杆菌为主。各类细菌对常用抗菌药物表现为高度多重耐药,临床应依据细菌病原学及耐药性资料合理选择抗菌药物。     

2016～2018年某基层三级综合医院院内感染病原菌分布及耐药率分析

目的:回顾性调查2016~2018年某基层三级综合医院院内感染病原菌分布和对常见抗菌药物的耐药率,为临床住院患者合理使用抗菌药物提供数据参考。方法:选择该院2016~2018年院感患者作为研究对象,分析院内感染的病原菌分布及耐药情况。结果:1650例感染患者,共检出病原菌1042株。院内感染病原菌检出数量前五位的分别为大肠埃希菌、铜绿假单胞菌、肺炎克雷伯菌、鲍曼不动杆菌及金黄色葡萄球菌;院内感染部位前3位为泌尿道,手术切口和下呼吸道;大肠埃希菌、肺炎克雷伯菌和阴沟肠杆菌对氨苄西林的耐药性均为最高,对碳青霉烯类抗菌药物较为敏感。肺炎克雷伯菌除对氨苄西林的耐药情况比大肠埃希菌严重以外,对其他药物耐药率均较大肠埃希菌低。阴沟肠杆菌对头孢唑林和头孢呋辛耐药率超75%,对其余药物耐药率均低于15%。鲍曼不动杆菌对大多数抗菌药物的耐药率较高,在70%以上。铜绿假单胞菌对庆大霉素耐药率100.00%,对阿米卡星耐药率2.38%。屎肠球菌与粪肠球菌对青霉素及庆大霉素耐药率较高,均未发现对万古霉素耐药。表皮葡萄球菌及金黄色葡萄球菌对青霉素、苯唑西林耐药率较高,对利奈唑胺、万古霉素和左氧氟沙星未见耐药。结论:院内感染病原菌种类较为固定,病原菌耐药形势严峻,应加强抗菌药物临床应用管理及院感防控措施,多方协作以减少耐药菌株在院内传播。     

某院血流感染患者血标本中病原菌的分布与耐药性分析

目的：分析医院血流感染患者血标本中病原菌的分布与主要病原菌的耐药特点,为临床用药提供参考。方法：选取2019年1月—2020年12月长葛市人民医院收治的242例血流感染患者作为研究对象,分析患者血标本中病原菌的分布与主要病原菌的耐药情况。结果：242例血流感染患者血标本中共检出病原菌291株,其中以大肠埃希菌（121株,占41.58%）、肺炎克雷伯菌（34株,占11.68%）和金黄色葡萄球菌（32株,占11.00%）为主;291株病原菌主要检出自感染/肿瘤科（131株,占45.02%）和呼吸内科（41株,占14.09%）;药敏结果显示,大肠埃希菌对除复方磺胺甲噁唑、头孢曲松、头孢呋辛、左氧氟沙星外的所有抗菌药物的耐药率均小于30.00%,肺炎克雷伯菌对所有抗菌药物的耐药率均小于30.00%;金黄色葡萄球菌对达托霉素、复方磺胺甲噁唑、拉氧头孢、利福平、利奈唑胺、莫西沙星、庆大霉素、替加环素、替考拉宁、头孢西丁、头孢唑林、万古霉素、克林霉素、左氧氟沙星的耐药率均小于30.00%。结论：医院血流感染患者的病原菌主要为大肠埃希菌、肺炎克雷伯菌和金黄色葡萄球菌,当前其对多数抗菌药物的耐药性尚不太...     

2017-2018年成都市温江区人民医院血流感染病原菌的分布及耐药性分析

目的 了解成都市温江区人民医院血流感染病原菌的分布及耐药性,指导临床合理用药,减少院内感染。方法 回顾性分析2017-2018年成都市温江区人民医院血流感染病原菌的分布及耐药情况。结果 共分离出病原菌229株,其中革兰阴性菌164株,占71.62%,主要为大肠埃希菌、肺炎克雷伯菌;革兰阳性菌59株,占25.76%,主要为金黄色葡萄球菌、凝固酶阴性葡萄球菌;真菌6株,占2.62%。大肠埃希菌对氨苄西林、氨苄西林/舒巴坦、头孢菌素、复方新诺明、喹诺酮类的耐药率均较高,且呈上升趋势;对阿米卡星、米诺环素、呋喃妥因、碳青霉烯类药物的耐药率均较低,且呈下降趋势。肺炎克雷伯菌虽对多数抗菌药物的耐药率低于10%,但对大部分抗菌药物的耐药率呈上升趋势。金黄色葡萄球菌对青霉素的耐药率极高,且呈上升趋势。凝固酶阴性葡萄球菌对大部分抗菌药物的耐药率均较高,但对大环内酯类的耐药率呈下降趋势。葡萄球菌中均未检出耐万古霉素、替考拉宁、利奈唑胺、呋喃妥因、阿米卡星菌株。结论 成都市温江区人民医院血流感染的病原菌主要为革兰阴性菌,对常用抗菌药物表现不同耐药性,临床应建立完善抗菌药物监测体系,合理使用抗菌药物。     

2018-2020年某医院血培养病原菌分布及耐药性分析

目的 了解2018—2020年南阳市第二人民医院血培养分离病原菌的分布及药物敏感性的变化,为临床抗感染治疗提供依据。方法 回顾性分析2018—2020年南阳市第二人民医院所有血培养阳性患者的病原菌分布及药敏结果,采用WHONET5.6及SPSS 25.0软件对结果进行统计分析。结果?共送检血培养9543份,分离出病原菌937株,阳性检出率为9.8%。其中革兰阳性菌446株(47.6%),革兰阴性菌477株(50.9%),真菌14株(1.5%)。革兰阳性菌主要检出细菌为表皮葡萄球菌,金黄色葡萄球菌,人葡萄球菌;革兰阴性菌主要检出细菌为大肠埃希菌,肺炎克雷伯菌。2018—2020年,除凝固酶阴性葡萄球菌对克林霉素的耐药率下降外(P<0.05),金黄色葡萄球菌和凝固酶阴性葡萄球菌对抗菌药物的耐药率差异无统计学意义(P>0.05)。耐甲氧西林金黄色葡萄球菌(MRSA)占53.2%。未检出对万古霉素、利奈唑胺、替考拉宁耐药的葡萄球菌。大肠埃希菌对除阿米卡星外的其他抗菌药物的耐药率差异均无统计学意义(P>0.05),肺炎克雷伯菌对除复方磺胺甲恶唑的耐药率均明显下降(P<0....     

我院儿科2015-2017年痰培养病原菌分布及耐药性分析

目的：了解我院儿科患儿痰培养病原菌分布及耐药情况,为临床合理使用抗菌药物提供参考。方法：筛选出我院儿科2015-2017年做痰培养检查的出院病例,对分离的病原菌及其耐药性进行分析与总结。结果：3 900份标本共检出病原菌1 003株（阳性率25.72%）,其中革兰阳性菌351株（35.00%）,革兰阴性菌617株（61.52%）,真菌35株（3.49%）;检出菌排名前5位的分别是大肠埃希菌260株（25.92%）、肺炎链球菌239株（23.83%）、肺炎克雷伯菌141株（14.06%）、金黄色葡萄球菌107株（10.67%）和流感嗜血杆菌64株（6.38%）。革兰阳性菌对红霉素、克林霉素和青霉素的耐药率高,其中肺炎链球菌对红霉素的耐药率为97.91%,金黄色葡萄球菌对青霉素的耐药率为96.33%。革兰阴性菌对第三代、第四代头孢菌素、含酶抑制剂的β-内酰胺类、单环β-内酰胺类、碳青霉烯类药物的耐药率较低,其中大肠埃希菌和肺炎克雷伯菌对头孢他啶的耐药率分别为13.85%和36.62%。耐甲氧西林金黄色葡萄球菌（MRSA）的检出率为15.89%,产超广谱β-内酰胺酶（ESBLs）的大肠埃希菌和肺炎克雷伯菌检出率分别为48.46%和51.06%。结论：我院儿科住院患者痰培养检出的病原菌以革兰阴性菌为主,不同病原菌对常用抗菌药物的耐药性不同,临床可参考细菌药敏试验结果选用抗菌药物,以提高疗效,减少耐药菌株的产生。     

佛山市中医院重症医学科痰液病原菌分布及耐药性分析

目的了解佛山市中医院重症医学科(ICU)近3年痰液标本的病原菌分布情况及对抗菌药物的耐药性,为指导临床合理用药提供参考依据。方法选取2017年1月1日至2019年10月17日佛山市中医院ICU合格痰液标本分离的病原菌与药敏进行回顾性调查分析。结果共分离出748株病原菌,其中革兰阴性菌579株,占77.41%,主要以鲍曼不动杆菌、铜绿假单胞菌、肺炎克雷伯菌、大肠埃希菌为主;革兰阳性菌113株,占15.11%,主要为金黄色葡萄球菌、肺炎链球菌;酵母样真菌56株,占7.48%,主要以白假丝酵母菌为主。鲍曼不动杆菌对大多数抗菌药物的耐药率大于70.00%,其中对美罗培南、亚胺培南耐药率高达91.26%、93.20%;铜绿假单胞菌对多粘菌素B高度敏感,对美罗培南、亚胺培南的耐药率分别为36.41%、39.81%;肺炎克雷伯菌对亚胺培南耐药率为9.33%,对多粘菌素B高度敏感;大肠埃希菌对美罗培南、亚胺培南的耐药率均为0.00%;金黄色葡萄球菌对苯唑西林耐药率为35.48%,未发现耐万古霉素及利奈唑胺的金黄色葡萄球菌;白假丝酵母菌对酮康唑、5-氟胞嘧啶的耐药率均为3.23%,对其他监测抗菌药物均高度敏感。结论佛山市中医院ICU痰液标本感染病原菌以革兰阴性菌为主,不同细菌的耐药率有所不同,特别是鲍曼不动杆菌、铜绿假单胞菌对碳青霉烯类抗菌药物呈现高耐药性,临床必须合理使用抗菌药物。     

2017—2020年柳州某医院血流感染病原菌变迁及耐药性分析

目的 分析连续4年的血流感染(Bloodstream infection, BSI)的病原菌分布及主要病原菌耐药性,为BSI的经验性治疗和院内感染防控提供参考依据。方法 回顾分析我院2017年1月至2020年12月分离的血培养阳性的标本,对病原菌的构成及主要病原菌的药敏进行分析,采用Whonet 5.6软件进行耐药统计分析。结果 2017—2020年共检出病原菌2 473株,主要来自重症医学科、普外科和肾内科等,其中革兰阳性菌544株(占22.0%),革兰阴性菌1 786株(72.2%)。前3位分离菌为大肠埃希菌942株(38.1%),肺炎克雷伯菌373株(15.1%),金黄色葡萄球菌214株(8.7%)。大肠埃希菌和肺炎克雷伯菌产超广谱β-内酰胺酶(ESBLs)检出率分别为40%和20%左右。大肠埃希菌在2017—2018年有3例碳青霉烯类耐药,2019—2020年无碳青霉烯类耐药。肺炎克雷伯菌在2019年有1例碳青霉烯类耐药,其余3年无碳青霉烯类耐药。金黄色葡萄球菌对万古霉素、利奈唑胺、奎奴普丁/达福普汀和替加环素均为敏感,耐甲氧西林金黄色葡萄球菌(MRSA)检出率为20%左右。结...     

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.