青藤碱肠溶片在Beagle犬体内药动学研究

目的:研究口服青藤碱肠溶片在Beagle犬体内的药动学。方法:8只Beagle犬口服青藤碱肠溶片(10mg·kg-1)0、15、30、60、90、120、240、480min后分别从前肢静脉取血2mL,采用高效液相色谱法测定并计算血药浓度,用3p97软件计算药动学参数。结果:青藤碱肠溶片在犬体内药-时曲线符合一室模型,主要药动学参数tmax为(69.66±16.41)min,Cmax为(0.13±0.02)μg·mL-1,t1/2ke为(87.62±28.26)min,AUC0～T为(28.43±3.48)μg·min·mL-1。结论:Beagle犬口服青藤碱肠溶片后在体内吸收迅速,消除较快。     

西嗪伪麻缓释片多次给药后伪麻黄碱的人体药动学研究

目的:研究健康受试者多次口服国产西嗪伪麻缓释片后伪麻黄碱的药动学特点。方法:10名健康受试者(男女各半),每次空腹口服西嗪伪麻缓释片(含伪麻黄碱120mg)1片,bid,连续6d。应用液-质联用(LC-MS)法测定血浆中伪麻黄碱浓度,所测数据用DASver2.0程序处理,然后进行药动学研究。结果:多次口服西嗪伪麻缓释片后伪麻黄碱主要药动学参数为t1/2(6.06±0.67)h,tmax(3.90±0.99)h,Cmax(272.03±52.56)ng·mL-1,CL(58.70±16.80)L·h-1,Vd(255.30±71.20)L,AUC0～36(3419.70±750.80)ng·h·mL-1,AUC0～∞(3422.20±751.00)ng·h·mL-1,MRT0～36(9.45±0.61)h,MRT0～∞(9.47±0.61)h。多次口服受试制剂3d后,伪麻黄碱血药浓度达稳态,其稳态药动学参数为Cssmax(272.03±52.56)ng·mL-1,Cssmin(104.99±37.15)ng·mL-1,Cssav(198.55±38.95)ng·mL-1,DF(0.86±0.20),AUCss(2382.61±467.44)ng·h·mL-1。以上参数男女比较均无显著性别差异,另多次和单次给药所得药动学参数比较均无统计学意义。受试者服药期间未出现明显不良反应。结论:西嗪伪麻缓释片中伪麻黄碱有明显的缓释效果;多次给药后伪麻黄碱的药动学过程无明显改变,在正常人体内无蓄积。     

高蛋白饮食对犬加替沙星药动学的影响研究

目的:研究高蛋白饮食对犬加替沙星药动学的影响。方法:8只Beagle犬随机交叉空腹或给予高蛋白饮食同时单次口服加替沙星胶囊17mg·kg-1,采用高效液相色谱法测定血药浓度,用3p97软件计算两者的药动学参数并比较评价。结果:空腹组和高蛋白饮食组的药-时曲线符合口服吸收一室摸型,主要药动学参数分别为t1/2ke(4.00±0.84)、(9.28±1.32)h;tmax(2.29±1.08)、(4.98±2.76)h;Cmax(6.06±0.87)、(3.42±1.20)μg·mL-1;AUC(0～t)(56.74±10.80)、(68.66±15.92)μg.h.mL-1,2组比较各参数均有显著性差异(P<0.05或P<0.01)。结论:高蛋白饮食明显影响犬加替沙星药动学参数。     

脂质饮食对犬体内莫昔沙星药动学的影响

目的:研究脂质饮食对莫昔沙星药动学的影响。方法:8只Beagle犬分别在空腹或脂质饮食状态下灌服莫昔沙星胶囊17mg·kg-1,1周后交叉实验;采用高效液相色谱法测定不同时间(72h内)血药浓度,用3p97软件计算二者的药动学参数并进行比较。结果:Beagle犬空腹组和脂质饮食组的药-时曲线分别符合二室模型和一室模型;空腹和脂质饮食状态下莫昔沙星主要药动学参数t1/2(βt1/2ke)分别为(24.89±6.77)、(12.32±2.96)h,tmax分别为(2.00±0.76)、(9.00±1.85)h,Cmax分别为(7.07±0.67)、(4.16±1.32)μg·mL-1,AUC0～t分别为(84.30±10.86)、(85.78±27.38)μg·h·mL-1;除AUC0～t外,其余各参数两两比较均有显著性差异(P<0.01)。结论:脂质饮食可明显延迟莫昔沙星的吸收,不利于其抗菌作用的发挥。     

碳水化合物对犬加替沙星药动学的影响

目的:研究碳水化合物饮食对犬加替沙星药动学的影响。方法:8只Beagle犬随机交叉空腹或摄取碳水化合物后单次口服加替沙星胶囊17mg·kg-1,采用高效液相色谱法测定血药浓度,用3p97软件计算两者的药动学参数,并评价碳水化合物饮食对加替沙星药动学的影响。结果:空腹组、摄食组的药-时曲线符合口服吸收一室模型,主要药动学参数分别为t1/2ke(4·00±0·84)、(3·98±1·10)h,tmax(2·29±1·08)、(3·45±2·00)h,Cmax(6·06±0·87)、(4·46±2·10)μg·mL-1,AUC(0~t)(56·74±10·80)、(45·99±6·47)μg·h·mL-1(P>0·05)。结论:碳水化合物饮食对犬加替沙星药动学参数无明显影响。     

马来酸咪达唑仑片在汉族健康人体内的药动学研究

目的:研究马来酸咪达唑仑片在汉族健康人体内的药动学。方法:10名汉族健康受试者口服马来酸咪达唑仑片15mg后,用高效液相色谱法测定咪达唑仑血药浓度,用DAS2.0药动学软件拟合药动学参数。结果:受试者单剂量口服马来酸咪达唑仑片后的主要药动学参数分别为Cma(x103.11±26.37)ng·mL-1、tma(x1.52±0.75)h、t1/(22.96±0.77)h、Vz/F(170.08±50.97)L、CL/F(41.05±12.33)L·h-1、AUC0～1(2368.80±103.37)ng·h·mL-1、AUC0～∞(397.29±124.06)ng·h·mL-1。部分受试者的药-时曲线存在双峰现象。结论:咪达唑仑片的药动学参数个体差异较大,临床应用时应注意个体化给药。     

2种丙泊酚注射液犬体内药动学研究

目的:比较2种丙泊酚制剂在犬体内的药动学情况。方法:12只Beagle犬随机交叉单次静脉注射丙泊酚微乳注射液或丙泊酚脂肪乳注射液4mg·kg-1后,采用高效液相色谱法测定丙泊酚血药浓度,用3p97软件计算主要药动学参数,并进行比较。结果:丙泊酚微乳注射液和丙泊酚脂肪乳注射液的药-时曲线均呈二室模型,二者t1/2β分别为(46.40±41.77)、(62.75±51.85)min;AUC(0～)t分别为(27.67±9.60)、(21.90±10.10)μg·min·mL-1,AUC(0～∞)分别为(29.33±13.55)、(28.66±13.76)μg·min·mL-1;经方差分析、双单侧t检验及(1-2α)置信区间法统计分析,药动学参数AUC(0～∞)间无显著性差异(P>0.05)。结论:2种丙泊酚制剂在犬体内的药动学过程相近。     

碳水化合物对犬体内莫昔沙星药动学的影响

目的:研究碳水化合物饮食对莫昔沙星药动学的影响。方法:8只Beagle犬分别在空腹或碳水化合物饮食状态下灌服莫昔沙星胶囊17mg·kg-1,1周后交叉实验;采用高效液相色谱法测定不同时间(72h内)血药浓度,用3p97软件计算二者的药动学参数并进行比较。结果:空腹和碳水化合物饮食状态下莫昔沙星主要药动学参数t1/2(βt1/2Ke)分别为(24.89±6.77)、(13.66±2.32)h;tmax分别为(2.00±0.76)、(9.15±7.28)h;Cmax分别为(7.07±0.67)、(8.48±3.81)μg·mL-1;AUC0～t分别为(84.30±10.86)、(169.13±47.03)μg·h·mL-1,除Cmax外,其余各参数两两比较均有显著性差异(P<0.01)。结论:碳水化合物饮食可延缓莫昔沙星在Beagle犬体内的吸收,但可增加吸收总量。     

雷贝拉唑钠肠溶胶囊Beagle犬体内药动学及生物等效性研究

目的：建立HPLC-MS测定方法分析Beagle犬血浆中雷贝拉唑的含量,并作不同厂家两种雷贝拉唑钠肠溶胶囊的药动学及生物等效性研究。方法：6只Beagle犬随机分为两组,采用单剂量双周期交叉试验,分别口服给予60 mg雷贝拉唑钠肠溶胶囊受试制剂或参比制剂,给药后不同时间点采血,测定血药浓度,利用DAS3.0软件计算药动学参数,并比较两个厂家生产的制剂的生物等效性。结果：Beagle犬单次给予雷贝拉唑钠肠溶胶囊受试制剂和参比制剂后的tmax分别为（3.57±0.91）h和（3.43±0.87）h,Cmax分别为（539.03±129.13）ng·mL-1和（554.90±135.75）ng·mL-1,t1/2分别为（2.20±0.90）h和（2.09±0.78）h,药时曲线下面积AUC（0→24 h）分别为（1341.40±442.03）ng·h·mL-1和（1319.41±402.29）ng·h·mL-1。结论：结果表明不同厂家的两种雷贝拉唑钠肠溶胶囊具有生物等效性。     

脂质饮食对加替沙星药动学的影响

目的:研究脂质饮食对加替沙星药动学的影响。方法:8只Beagle犬随机交叉空腹或给予脂质饮食同时单次口服加替沙星胶囊17mg·kg-1,采用高效液相色谱法测定血药浓度,用3p97软件计算两者的药动学参数,并评价脂质饮食对加替沙星药动学的影响。结果:空腹组和脂质饮食组的药-时曲线符合口服吸收一室模型,主要药动学参数t1/2Ke分别为(4.00±0.84)、(7.87±1.54)h;tm ax分别为(2.29±1.08)、(3.61±2.72)h;Cm ax分别为(6.06±0.87)、(2.91±1.27)μg·mL-1;AUC(0~t)分别为(56.74±10.80)、(45.35±10.81)μg.h.mL-1,其中t1/2ke、Cm ax比较均有显著性差异(P<0.05或P<0.01)。结论:脂质饮食明显影响加替沙星药动学参数。     

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。     

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。     

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。     

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.     

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.     

基层医院护士在临床合理用药中的作用

目的充分利用护士在医师和患者间的特殊地位和作用,促进基层临床合理用药。方法从护士的工作性质出发,论述护士参与促进合理用药的方便和优势。结果通过实践,护士在促进合理用药中的作用得到有效发挥,基层合理用药环境得到极大改善。结论充分利用护士与医师和患者间的特殊桥梁作用,在基层医院促进合理用药,规范医师用药行为,防止药物滥用,引导患者安全用药,降低药源性疾病。