匹伐他汀治疗原发性高胆固醇血症的疗效与安全性评价

目的 评价匹伐他汀治疗原发性高胆固醇血症的疗效和安全性.方法 随机、单盲(对研究者设盲)、阳性药物平行对照.46例原发性高胆固醇血症患者随机分为匹伐他汀(2和4 mg)组和阿托伐他汀(10 mg)组,研究为期8周,观察治疗前后患者血脂[总胆固醇(TC)、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDL-C)、甘油三酯(TG)]、丙氨酸氨基转移酶/天冬氨酸氨基转移酶(ALT/AST)及磷酸肌酸激酶(CPK)水平的变化.结果 治疗4和8周各组TC、LDL-C水平均明显降低(P<0.01), 且4周与8周无显著差异;治疗8周各组LDL-C达标率分别为62.5%、66.7%和86.7%;但3组HDL-C和TG水平治疗前后无明显变化.匹伐他汀(2 mg)组1例出现CPK水平异常升高,停药2周后恢复正常.结论 匹伐他汀能有效降低原发性高胆固醇血症患者的TC和LDL-C水平,疗效与阿托伐他汀相似,且基本安全.     

匹伐他汀钙片治疗高胆固醇血症的有效性和安全性研究

目的 评价匹伐他汀钙片治疗高胆固醇血症的有效性和安全性.方法 360例高胆固醇血症患者接1∶1∶1比例随机分为匹伐他汀钙片l mg组、2 rng组和阿托伐他汀钙片10 mg组,经4周筛选期后,符合入选标准的患者接受l mg/2 mg匹伐他汀钙片或10 mg阿托伐他汀钙片治疗(一日1次,口服),治疗8周,观察各组治疗前后血清低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、总胆固醇(TC)和甘油三酯(TG)变化情况.结果 治疗8周后各组LDL-C下降显著,分别为-30.06％、-35.04％和-34.34％,组间差异无统计学意义.匹伐他汀钙片2 mg组降低LDL-C的疗效非劣于阿托伐他汀钙片组,匹伐他汀钙片1 mg组降低LDL-C的疗效劣于阿托伐他汀钙片组.治疗4、8周后匹伐他汀钙降低TC、HDL-C和TG作用与阿托伐他汀钙比较差异无统计学意义.结论 匹伐他汀钙片治疗高胆固醇血症安全有效.     

阿托伐他汀联合非诺贝特治疗混合型高脂血症的Meta分析

目的系统评价阿托伐他汀联合非诺贝特治疗混合型高脂血症的疗效与安全性。方法计算机检索Cochrane、Pub Med、CBM、万方、CNKI及维普全文电子期刊数据库中随机对照试验。结果共纳入15项随机对照试验,1980例患者。联合治疗组对总胆固醇(TC)、三酰甘油(TG)和高密度脂蛋白胆固醇(HDL-C)的疗效优于单药治疗组;与单药治疗组相比,未增加药物不良反应(ADR);剂量分组分析结果显示,联合治疗组用常规剂量与低剂量的阿托伐他汀联合非诺贝特治疗,安全性均良好[SMD=1.13,95%CI(0.57,2.24),P>0.05;SMD=1.50,95%CI(0.94,2.39),P>0.05]。阿托伐他汀与非诺贝特联合治疗组对TC、TG和HDL-C的疗效优于单药治疗[SMD=-11.10,95%CI(-18.44,3.77),P<0.05;SMD=-1.20,95%CI(-1.28,1.12),P<0.05;SMD=0.694,95%CI(0.587,0.801),P<0.05]。结论低剂量与常规剂量阿托伐他汀联合非诺贝特治疗混合型高脂血症安全性和有效性均良好。     

普罗布考与阿托伐他汀治疗高脂血症疗效比较

目的 比较普罗布考与阿托伐他汀治疗高脂血症的疗效. 方法 47例高脂血症患者随机分为治疗组25例,对照组22例.治疗组给予普罗布考0.5 g,po,bid,治疗8周;对照组给予阿托伐他汀10 mg ,po,qn,治疗8周.观察两组降脂疗效和不良反应. 结果 治疗组治疗后总胆固醇（TC）下降总有效率为76.0%,对照组为77.3%.治疗组 TC下降25.6%,低密度脂蛋白胆固醇（LDL-C）下降27.7%（P均< 0.01）,高密度脂蛋白胆固醇（HDL-C）下降23.1%,三酰甘油（TG）下降1.8%.对照组TC下降28.1%,LDL-C下降32.7%,HDL-C上升13.8%,TG下降20.8%.普罗布考降TC、LDL-C疗效与阿托伐他汀相似（ P> 0.05）.结论 普罗布考有明显降低TC、LDL-C的作用,疗效与阿托伐他汀相似,不良反应轻微,是安全有效的降胆固醇药物.     

瑞舒伐他汀与阿托伐他汀治疗高胆固醇血症的临床对比观察

目的：对比瑞舒伐他汀和阿托伐他汀治疗老年高胆固醇血症患者的临床疗效。方法将76例高脂血症患者随机分为研究组和对照组各38例。对照组予阿托伐他汀,研究组予瑞舒伐他汀。于每晚入睡前服用,分别于受试后的4周和8周随访,抽空腹肘静脉血,测定2组TC、TG、LDL-C、HDL-C。结果治疗前2组TC、TG、HDL-C、LDL-C水平差异无统计学意义（P＞0．05）。治疗后第4、8周2组TC、TG、LDL-C水平低于治疗前,HDL-C水平高于治疗前,且研究组优于对照组,差异均有统计学意义（P＜0．05）。研究组LDL-C达标率为89．5％高于对照组的76．3％,差异均有统计学意义（ P＜0．05）。结论瑞舒伐他汀组、阿托伐他汀组均能明显降低TC、TG、LDL-C,升高HDL-C,调脂疗效确切。瑞舒伐他汀的临床疗效优于阿托伐他汀,剂量更小,价格相对低廉,安全性相当,值得临床推广使用。     

不同剂量阿托伐他汀治疗颈动脉粥样硬化对比分析

目的 观察不同剂量阿托伐他汀对颈动脉粥样硬化的临床疗效.方法 选择存在有不同程度的颈动脉粥样硬化并有斑块形成的患者118例,随机分为2组.治疗组56例,服用阿托伐他汀20mg,每晚1次;对照组62例,服用阿托伐他汀10mg,每晚1次,疗程4个月(16周).观察治疗前后颈动脉内膜-中层厚度(IMT)以及胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)的变化.结果 阿托伐他汀10mg、20mg均能明显减轻颈动脉粥样硬化,降低TC、TG、LDL-C水平,升高HDL-C水平.治疗组较对照组能更进一步降低降低IMT(P＜0.05)、TC、LDL-C(P＜0.05)和升高HDL-C水平(P＜0.05).结论 阿托伐他汀可以明显减轻颈动脉粥样硬化病变,有效降低血脂水平,可作为治疗颈动脉粥样硬化的常规用药.     

阿托伐他汀对心肌梗死患者血脂水平的影响

目的 探讨阿托伐他汀对心肌梗死患者血脂水平的影响.方法 58例心肌梗死患者随机分为观察组(采用阿托伐他汀治疗,29例)及对照组(采用烟酸缓释片治疗,29例),比较分析两组患者血脂水平变化.结果 两组治疗前总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C)水平差异均无统计学意义(均P＞0.05);治疗后,两组TC、TG、LDL-C水平均有显著降低(t=8.56、7.98、9.12、9.95、8.02、7.64,均P＜0.05),且观察组TC、LDL-C水平显著低于对照组(=7.78、9.15,均P＜0.05).结论 阿托伐他汀对心肌梗死患者降脂疗效显著,安全可靠.     

瑞舒伐他汀与阿托伐他汀在治疗冠心病中的比较分析

目的探讨阿托伐他汀以及瑞舒伐他汀应用于冠心病患者的治疗效果以及安全性。方法选取冠心病患者92例,将患者按照随机数字表法分为阿托伐他汀组和瑞舒伐他汀组,每组46例。阿托伐他汀组予以阿托伐他汀20 mg/d口服治疗,瑞舒伐他汀组采用瑞舒伐他汀10 mg/d口服治疗。比较两组患者治疗前后的血浆血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),并统计血脂达标率。结果两组患者治疗后的TC、LDL-C水平均较治疗前明显改善,但是与阿托伐他汀组相比,瑞舒伐他汀组患者改善的幅度更加明显,组间比较差异有统计学意义(P<0.05)。结论采用2种他汀类药物均可以改善冠心病患者的血脂水平,但是瑞舒伐他汀在改善冠心病患者的血脂方面效果更好。     

阿托伐他汀与氟伐他汀治疗高胆固醇血症的对比研究

目的　探讨阿托伐他汀 (立普妥 )与氟伐他汀 (来适可 )对高胆固醇血症病人疗效及安全性。方法　 10 0例高胆固醇血症随机分成阿托伐他汀组 5 0例和氟伐他汀组 5 0例 ,治疗 6周后观察比较。结果　阿托伐他汀及氟伐他汀均能明显降低TC、TG、LDL C水平 (P <0 0 1或P <0 0 5 ) ,阿托伐他汀降TC、TG、LDL C的作用强于氟伐他汀 (P <0 0 5 ) ,两药均能升高HDL C水平 (P <0 0 5 ) ,但两组比较未达到显著差异 (P >0 0 5 )。两药不良反应均比较小 ,耐受性好。结论　阿托伐他汀降TC、TG、LDL C的作用优于氟伐他汀 ,但升高HDL C水平相似 ,两药均有良好的安全性。     

匹伐他汀治疗高胆固醇血症36例的临床疗效分析

目的 探讨匹伐他汀治疗高胆固醇血症的临床疗效.方法 将68例高胆固醇血症患者按盲目随机法分为两组,观察组36例使用匹伐他汀,对照组32例使用辛伐他汀.治疗结束后,将总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)、高密度蛋白胆固醇(HDL-C)水平进行对比.结果 两组TC与LDL-C降低程度与治疗前相比均有明显差异(P＜0.05),TG与HDL-C均无明显差异(P＞0.05).两组患者LDL-C水平的达标率与不良反应发生率均无明显差异(P＞0.05).结论 匹伐他汀治疗高胆固醇血症疗效显著,能有效降低TC及LDL-C水平,不良反应率低,安全水平高,值得临床推广.     

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。     

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.     

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.     

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.     

Study of potential in vitro and in vivo genotoxicity in hepatocytes of quinolone antibiotics

The genotoxicity of quinolone antibiotics has been evaluated in hepatocytes following in vitro and in vivo exposure. Unscheduled DNA synthesis (UDS) was induced in vitro in rat hepatocytes by norfloxacin, ofloxacin, pefloxacin, and ciprofloxacin but not by nalidixic acid. In vivo UDS was not observed in hepatocytes isolated 4 to 24 hr after exposure of adult male F344 rats to either a single dose (30 to 190 mg/kg) or repeated doses (40 mg/kg) of ciprofloxacin. Using the 32P-postlabeling technique, no modified bases were detected in hepatocytes exposed in vitro to ciprofloxacin. In summary, UDS was induced in hepatocytes by in vitro exposure to high concentrations of norfloxacin, ofloxacin, pefloxacin, or ciprofloxacin. There was no evidence of in vitro DNA adduct formation by ciprofloxacin or in vivo DNA damage under the conditions tested. These findings suggest that ciprofloxacin is not DNA reactive, but it induces in vitro UDS as a consequence of some indirect action.