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。     

我院2015年病原菌分布情况及耐药性分析

目的:为临床合理使用抗菌药物提供依据。方法:采用回顾性分析方法,对我院2015年1-12月病原菌分布、构成及耐药情况进行统计分析。结果:2015年我院检验科微生物室共收到标本9 401份,检出病原菌的标本共1 743份,阳性率为18.54%;共检出病原菌1 591株,主要来源于痰液(59.77%)、尿液(14.77%)和血液标本(8.93%)。共检出革兰氏阳性菌347株(21.81%)、革兰氏阴性菌991株(62.29%)和真菌253株(15.90%);检出量列前4位的分别为大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌和金黄色葡萄球菌。金黄色葡萄球菌、肺炎链球菌和溶血葡萄球菌对万古霉素、利奈唑胺和夫西地酸钠敏感,耐药率均为0;对红霉素的耐药率均超过65%。金黄色葡萄球菌对青霉素的耐药率超过95%,溶血葡萄球菌对常用抗菌药物的耐药率普遍较高。大肠埃希菌、肺炎克雷伯菌和铜绿假单胞菌对碳青霉烯类药物的耐药率均低于15%,且均对多黏菌素敏感,耐药率为0。大肠埃希菌对喹诺酮类药物的耐药率均超过50%。结论:我院病原菌感染以革兰氏阴性菌为主,整体耐药情况不容乐观。对主要病原菌敏感性较高的药物包括万古霉素、利奈唑胺和碳青霉烯类等。临床应加强对病原菌耐药特征的监测,并根据药敏试验结果合理、规范地选用抗菌药物。     

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。     

基层医院产ESBLs 病原菌耐药性分析

目的 分析致病菌中产超广谱β-内酰胺酶(ESBLs)的大肠埃希菌和肺炎克雷伯菌的耐药性,为临床合理使用抗菌药物提供依据.方法 对688株致病菌检验结果进行统计学分析,了解产ESBLs病原菌的耐药情况.结果 致病菌688株中革兰氏阴性菌392株占57.0%,其中大肠埃希菌和肺炎克雷伯菌共179株占45.7%,产ESBLs大肠埃希菌和肺炎克雷伯菌共84株,产酶率为46.9%(84/179),其对青霉素类和1、2、3代头孢菌素高度耐药,对亚胺培南、美罗培南高度敏感.结论 大肠埃希菌和肺炎克雷伯菌是产ESBLs的主要阴性杆菌,碳青霉烯类抗生素亚胺培南、美罗培南等是治疗产ESBLs菌感染的较佳药物.     

基层医院产ESBLs病原菌耐药性分析

目的分析致病菌中产超广谱β-内酰胺酶(ESBLs)的大肠埃希菌和肺炎克雷伯菌的耐药性,为临床合理使用抗菌药物提供依据。方法对688株致病菌检验结果进行统计学分析,了解产ESBLs病原菌的耐药情况。结果致病菌688株中革兰氏阴性菌392株占57.0%,其中大肠埃希菌和肺炎克雷伯菌共179株占45.7%,产ESBLs大肠埃希菌和肺炎克雷伯菌共84株,产酶率为46.9%(84/179),其对青霉素类和1、2、3代头孢菌素高度耐药,对亚胺培南、美罗培南高度敏感。结论大肠埃希菌和肺炎克雷伯菌是产ESBLs的主要阴性杆菌,碳青霉烯类抗生素亚胺培南、美罗培南等是治疗产ESBLs菌感染的较佳药物。     

安阳地区住院儿童肺炎常见病原菌及耐药性分析

目的了解本地区儿童肺炎常见病原菌及耐药情况,指导临床合理用药。方法对安阳市儿童医院2010年1月至2011年3月住院的肺炎患儿的5511份痰培养结果进行回顾性分析,将所有标本中分离得到的病原菌数量较多的前7种作为常见病原菌,进行药敏试验,并分别按菌属及季节进行耐药情况分析。结果共检出常见病原菌2801株,阳性检出率为50.83%。其中革兰氏阳性菌为969株,占35.51%(肺炎链球菌522株,占18.64%,金黄色葡萄球菌447株,占15.96%);革兰氏阴性菌共1673株,占59.73%(克雷伯菌属共581株,占20.74%,大肠埃希菌417株,占14.89%,肠杆菌属282株,占10.07%,鲍曼不动杆菌属160株,占5.71%,大肠埃希菌417株,占14.89%,铜绿假单胞菌127株,占4.53%,假单胞菌39株,占1.39%,液化沙雷菌32株,占1.14%);其他菌属35株,占1.25%;真菌159株,占5.68%。在检出的病原菌中产超光谱β-内酰胺酶(ES-BLs)菌株有206株,占12.31%;耐甲氧西林金黄色葡萄球菌(MRSA)10株,占2.24%。药敏试验显示革兰氏阳性菌中以肺炎链球菌为主,对万古霉素敏感,对克林霉素、阿莫西林、红霉素耐药;金黄色葡萄球菌对青霉素、阿奇霉素、克林霉素都耐药,对万古霉素敏感。革兰氏阴性菌以克雷伯菌属、肠杆菌科其他菌属为主,其中产超光谱β-内酰胺酶(ESBLs)菌株,敏感的抗生素依次为亚胺增南、头孢哌酮/舒巴坦、哌拉西林/他唑巴坦,耐药性较高的依次为阿莫西林棒酸、哌拉西林、头孢唑啉、头孢呋辛、头孢他啶、氨曲南。结论本地区住院肺炎患儿常见病原菌以克雷伯菌、肺炎链球菌、金黄色葡萄球菌、大肠埃希菌为主,其中革兰氏阴性杆菌中产超光谱β-内酰胺酶(ESBLs)菌株对亚胺培南、头孢哌酮/舒巴坦、哌拉西林/他唑巴坦具有较高的敏感性。检出的耐甲氧西林金黄色葡萄球菌菌对方万古霉素敏感。其他药物耐药率较高。     

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...     

2012—2019年某院血培养分离菌的分布及耐药性分析

摘要：目的 了解福建省龙岩市第一医院2012—2019年血培养分离菌的分布及其对常用抗菌药物的耐药情况。方法 采用美国BD Phoenix 100细菌鉴定仪和纸片扩散法对临床送检的血培养分离菌进行鉴定和药敏试验,应用WHONET 5.6软件进行数据统计分析。结果 8年间共分离病原菌3008株(剔除重复菌株),其中革兰阴性菌2173株,占72.2%,革兰阳性菌743株,占24.7%,真菌92株,占3.1%。居前6位的分别是大肠埃希菌(40.0%)、肺炎克雷伯菌(15.4%)、金黄色葡萄球菌(8.2%)、肺炎链球菌(3.7%)和铜绿假单胞菌(3.3%),凝固酶阴性葡萄球菌(2.9%)。耐甲氧西林金黄色葡萄球菌(MRSA)和凝固酶阴性葡萄球菌(MRCNS)分别占各自菌的34.3%和90.7%,未发现对利奈唑胺、替考拉宁、万古霉素耐药的葡萄球菌。粪肠球菌对青霉素和氨苄西林耐药率低,粪肠球菌和屎肠球菌未发现对万古霉素和替考拉宁耐药。未发现对左氧氟沙星、莫西沙星、利奈唑胺和万古霉素耐药的肺炎链球菌。产ESBLs大肠埃希菌和肺炎克雷伯菌分别占各自菌41.6%和19.0%,大肠埃希菌和肺炎克雷伯菌对阿米卡星、阿莫西林/克拉维酸、哌拉西林/三唑巴坦、头孢哌酮/舒巴坦的耐药率均在6%以下;出现对碳青霉烯类耐药肠杆菌科细菌(CRE),大肠埃希菌、肺炎克雷伯菌、阴沟肠杆菌对碳青霉烯类耐药率分别为0.3%、1.1%和1.6%。铜绿假单胞菌对常用抗菌药物的耐药率在12%以下,对碳青霉烯类耐药率为7.0%。鲍曼不动杆菌的对常用抗菌药物耐药率较高,处于30%~50%。结论 血培养分离菌以革兰阴性菌为主,大肠埃希菌和肺炎克雷伯菌是血培养中最常见的分离菌。肺炎克雷伯菌所占比例在2012—2019年有不断上升趋势。应加强与临床沟通,注重血培养规范送检和医院感染控制,重视血培养分离菌的耐药监测工作,加强抗生素的合理使用。     

2009年重庆医科大学附属第一医院细菌耐药监测

目的 调查我院2009年临床分离病原菌对抗菌药物的耐药性.方法 采用纸片扩散法进行抗菌药物敏感实验,采用WHONET5.4软件及SPSS13.0软件进行数据分析.结果 临床分类的1608株病原菌中,革兰阳性菌占25.1%,革兰阴性菌占74.9%:耐甲氧西林金黄色葡萄球菌和凝固酶阴性葡萄球菌株检出率分别为63.7%和93.7%:未发现对万古霉素或替考拉宁中介或耐药的葡萄球菌和肠球菌菌株.大肠埃希菌、肺炎克雷伯菌ESBLs检出率分别为57.2%、56.8%,肺炎克雷伯菌ESBLs的菌株高于2008年监测比例,且差别具有统计学意义(P<0.05).鲍曼不动杆菌对碳青霉烯类抗菌药物的耐药率在55%以上.结论 革兰阳性细菌对万古霉素、替考拉宁、利奈唑胺均敏感;肠杆菌对碳青霉烯类敏感性高;铜绿假单胞菌对阿米卡星敏感、头孢哌酮/舒巴坦相对敏感,鲍曼不动杆菌对碳青霉烯类耐药率高,对头孢哌酮/舒巴坦敏感性高.未发现泛耐药菌株.     

Mohnarin 2008年度报告:中南地区细菌耐药监测

目的 分析中南地区2008年临床分离菌对常用抗菌药物的耐药情况.方法 采用纸片扩散法进行抗菌药物敏感性试验. 结果中南地区11所三级甲等医院共分离32891株细菌,革兰阴性菌占70.3%,革兰阳性菌占29.6%.前10位病原菌依次为大肠埃希菌、铜绿假单胞菌、肺炎克雷伯菌、鲍曼不动杆菌、金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌、阴沟肠杆菌、屎肠球菌、溶血葡萄球菌.耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(MRSCN)的检出率分别为62.1%和83.6%.耐万古霉素和/或替考拉宁的肠球菌17株,分离率0.7%.大肠埃希菌、克雷伯菌属(肺炎克雷伯菌和产酸克雷伯菌)和奇异变形菌中产ESBLs株分离率分别为59.3%、37.5%和6.3%,儿童组(≤14岁)大肠埃希菌和克雷伯菌属(肺炎克雷伯菌和产酸克雷伯菌)产ESBLs株分离率为70.9%和64.9%,成人组(>14岁)为58.4%和35.0%.碳青霉烯类耐药肠杆菌科细菌检出率为0.7%.不动杆菌属细菌对亚胺培南和美罗培南的敏感率分别为53.8%和55.7%,铜绿假单胞菌敏感率分别为71.8%和76%.嗜麦芽寡养单胞菌对左氧氟沙星和TMP/SMZ的敏感率为83.7%和81.9%.流感嗜血菌对TMP/SMZ和氨苄西林的敏感率较低,分别为40.8%和58.7%.儿童组产β-内酰胺酶流感嗜血菌分离率48.6%,明显高于成人组分离率22.0%(P<0.05).罕见β-内酰胺酶阴性而氨苄西林耐药的流感嗜血菌(BLNAR)15株,占4.1%.结论 临床常见病原菌仍以革兰阴性杆菌为主,细菌耐药性呈上升趋势.儿童组产ESBLs菌株较成人组高,出现少数耐万古霉素肠球菌、碳青霉烯类耐药肠杆菌科细菌及多重耐药革兰阴性杆菌,应引起重视.     

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.