某三甲医院依达拉奉注射液用药合理性调查

摘 要 目的：评价某院依达拉奉注射液临床应用合理性,提升临床合理用药水平。方法: 利用该院病案管理系统,随机提取2016年1～6月应用依达拉奉注射液病历500份,依据药品说明书、相关文献与资料分析其临床应用合理性。结果: 500份病历中神经外科占48%,神经内科37%,重症医学科7%,骨科5%,其他科室占3%。用药不合理病历共计261份（52.2%）;其中超说明书适应证用药108份（21.6%）;给药频次不当180份（36%）;给药疗程不当201份（40.2%）;给药时机不正确37份（7.4%）;溶媒选择错误3份（0.6%）;存在特殊人群使用4份（0.8%）。结论:依达拉奉注射液在该院存在严重的超疗程、超适应症使用等现象,且不能够严格遵照药品说明书规定的给药频次和注意事项合理用药,应引起高度重视。     

干预前后呼吸科应用大株红景天注射液的对比研究

摘 要 目的：通过对比干预前后呼吸科大株红景天注射液的应用情况,规范其临床使用并为药事管理提供参考。方法: 对使用大株红景天注射液的住院患者病历进行回顾性调查,针对发现的问题进行干预,对比干预前后呼吸科大株红景天注射液用药情况及其合理性。结果: 回顾性调查584例病历,其中超适应证用药438例（75.00%）,溶媒选择不适宜555例（95.03%）,疗程不适宜196例（33.56%）。干预后,溶媒不适宜改善率为98.70%,适应证不适宜改善率为29.85%,疗程不适宜的改善率为77.71%。结论: 通过干预前后对比研究能针对性找出干预问题,高效改正不适宜情况,其余药品的专项管理可以参考此种方式。     

某院紫杉醇注射剂用药情况与不良反应相关因素分析

摘 要 目的：分析紫杉醇注射剂用药情况及其不良反应相关因素,为临床合理用药提供参考。方法：回顾性分析某院2017年3月~ 2017年11月255例使用紫杉醇注射剂患者的用药情况如给药剂量、溶媒、紫杉醇剂型、化疗前是否进行预防用药和化疗方案等及其用药期间发生药品不良反应（ADR）的特点,并分析ADR的相关因素。结果：255例患者中男112例,女143例,平均年龄56.6岁,原发肿瘤主要为非小细胞肺癌、卵巢恶性肿瘤和头颈部癌,肿瘤TNM分期主要为Ⅳ期。紫杉醇单药化疗44例（17.25%）,联合化疗211例（82.75%）。紫杉醇适应证、给药剂量和溶媒等方面超说明书用药比例分别为53.72%、20.54%和10.10%。ADR发生率为81.96%,严重ADR占20.70%（94/454）。主要ADR类型为血液和淋巴系统疾病及骨骼肌和结缔组织,最常见WBC降低（25.11%）。对紫杉醇ADR发生率有显著性影响的因素包括患者所在科室、生产厂家及是否进行预防用药。结论：某院紫杉醇注射剂存在超说明书用药情况,但超说明书用药与ADR发生无相关性。几种联合化疗方案的ADR发生率差异无统计学意义,使用紫杉醇脂质体可能会减少ADR的发生。     

某院1 435例单唾液酸四己糖神经节苷脂钠应用合理性分析

摘 要 目的：了解某院单唾液酸四己糖神经节苷脂钠（GM1）的使用情况,分析其使用合理性,为临床合理用药提供参考。方法：采用回顾性分析方法,统计某院2018年1~6月住院患者的GM1使用情况,参照说明书及相关指南、共识进行合理性分析。结果：某院GM1平均药物利用指数（DUI）为1.22,使用量最多的为老年病科;1 435例患者中,适应证不合理242例（16.86%）,给药剂量不合理150例（10.45%）,用药疗程不合理206例（14.35%）,溶媒选择不合理52例(3.62%),配伍不合理4例（0.28%）,联合用药不合理16例（1.65%）。结论：GM1的使用存在不合理现象,其中适应证、给药剂量、用药疗程不合理问题较为突出,应提高GM1使用的合理性。     

某院201例注射用洛铂超说明书用药及其不良反应相关因素分析

摘 要 目的：分析注射用洛铂超说明书用药情况及其不良反应,为临床合理用药提供参考。方法: 应用SPSS统计软件,回顾性分析某院2016年11月～2017年7月201例使用注射用洛铂患者的用药情况及药品不良反应/事件（ADR/ADE）发生特点,并进行相关因素分析。结果:201例使用注射用洛铂患者的适应证、给药途径和溶媒等方面超说明书用药比例分别为89.55%、18.41%和47.26%。ADR发生率为63.18%。ADR/ADE主要表现为血液和淋巴系统损害及肝胆系统损害,如淋巴细胞计数降低（40.80%）、贫血（23.88%）、白细胞数降低（19.90%）、血小板计数降低（15.92%）和AST增高（10.45%）等,无5级ADR发生,有心悸、呼吸困难和呃逆等新的ADR发生。且0.9%氯化钠溶液为溶媒可能是ADR发生的危险因素。结论:该院注射用洛铂大部分超说明书用药,ADR发生率为63.18%,以0.9%氯化钠溶液为溶媒可能是发生ADR的危险因素。     

我院外科病房质子泵抑制药使用调查

摘 要 目的:了解质子泵抑制药在外科病房的使用情况并评价其用药合理性。方法：通过医院HIS系统统计我院外科住院患者2014年7～12月质子泵抑制药的使用情况,包括品种、数量、金额等,并计算各品种用药频度（DDDs）、限定日费用（DDC）等,同时按10%比例随机抽取病历进行合理性点评,并分析与用药趋势的相关性。结果：6个月中使用频度、金额均排第一的是注射用兰索拉唑;467 份使用质子泵抑制药的外科病历中,以预防溃疡为目的的占80.9%,其中无指征用药占比61.7%;给药途径、用法用量和用药疗程不合理的比例分别为60.9%、20.1%和18.4%,且用药频度、金额排序靠前的品种出现不合理用药的比例越多。结论：外科使用质子泵抑制药随意性较大,存在不合理使用现象,有必要制定使用规范,加强监督管理,促进合理用药。     

4 367例儿科住院不合理用药医嘱帕累托图分析

摘 要 目的：了解某院住院患者电子医嘱的不合理用药情况,促进临床合理用药。方法: 收集2015年1月~2017年6月某院住院患者不合理用药电子医嘱4 367例,对其类型、涉及的药物种类、具体品种进行统计,并采用帕累托图进行分析。结果: 该院住院患者不合理用药医嘱的主要类型为给药剂量不当（1 601例,36.67%）、给药途径或方式不当（545例,12.48%）、药物浓度不当（481例,11.01%）、输液速度不当（470例,10.76%）和溶媒选择不当或无（387例,8.86%）。不合理用药医嘱涉及的主要药物种类为抗菌药物（981例,22.46%）、电解质、维生素及营养药（663例,15.18%）、呼吸系统用药（532例,12.18%）、消化系统用药（446例,10.21%）、中成药（419例,9.59%）和血液系统用药（335例,7.67%）。结论: 针对该院住院患者不合理用药的主要原因,应加强对临床医师安全合理用药知识培训、建立持续改进措施、保证临床用药安全。     

600例儿童Ⅰ类切口围手术期预防应用抗菌药物调查

摘 要 目的：了解住院患儿清洁手术抗菌药物的预防使用情况,为规范抗菌药物的使用提供依据。方法：采用系统随机抽样的方法随机抽取2017年1～6月出院的600例Ⅰ类切口手术患儿,回顾性统计分析患者一般情况、手术类型与抗菌药物预防使用信息,评价抗菌药物预防使用合理性。结果：600例患儿抗菌药物使用率为40.7% ,术后给药时间＞48 h占54.3%,预防用药时机不合理为9.1%,预防用药给药剂量不合理为28.1%,预防使用抗菌药物的手术主要是涉及重要脏器如脑、脊髓及心脏等手术,但也有部分其他清洁手术预防使用抗菌药物。结论：儿童Ⅰ类切口手术围手术期预防性使用抗菌药的用药指征、给药时机、持续用药时间等存在不合理现象,表现为无指征用药、预防用药使用率偏高、抗菌药物选择不合理、首次给药时机不合理、术后用药持续时间过长等,提示Ⅰ类切口手术围手术期预防性使用抗菌药物仍有待进一步规范。     

880例妇科手术患者应用质子泵抑制剂合理性分析

摘 要 目的：调查某院妇科手术患者质子泵抑制药（PPIs）使用情况,分析PPIs预防应激性溃疡（SU）合理性,为临床正确使用PPIs提供参考。方法: 抽取2016年首次入住妇科病区的出院患者病历1000份,回顾性分析PPIs使用情况,评价其使用合理性。结果:PPIs预防使用率为90.72%（880/970）;28.18%（248/880）的患者不具备预防用药指征,95.68%（842/880）的患者给药时机错误,91.46%（578/632）的患者用法用量错误。结论:妇科手术患者使用PPIs预防SU时,存在适应证、品种选择、用法用量等方面的不合理现象,应加强技术和行政干预,制定符合本院实际情况的PPIs使用标准,改善PPIs不合理使用现状。     

206例乳腺癌患者抗肿瘤药物应用评价分析

摘 要 目的：评价医院乳腺癌患者抗肿瘤药物的使用情况,为临床合理用药提供参考。 方法：回顾性研究206例转移性乳腺癌患者治疗方案,依据药品说明书和临床实践指南对抗肿瘤药物使用的合理性进行评价。按照实体瘤的疗效评价标准(RECIST)评价有效性;按照不良事件评价标准 (CTACE4.03)分析安全性;对患者的住院费、药费和抗肿瘤药物费用进行统计分析。 结果：疗效评价表明客观缓解率为16.0%（33/206）,疾病控制率为65.0%（134/206）,疾病进展为7.8%（16/206）,未评价的患者为27.2%（56/206）。化疗方案选择合理为80.1%（165/206）,化疗方案无依据为19.9%（41/206）,给药途径与溶媒超说明书为4.8%（10/206）,平均相对剂量强度为89.6%。不良事件多为轻度,Ⅲ级以上严重不良事件发生率为3.0%。住院费用、药物费用、抗肿瘤药费中位数分别为7 870,6 082,3 983元。 结论：抗肿瘤药物疗效与不良反应发生率均偏低,可能与多个化疗方案平均剂量低于指南标准剂量相关;需进一步改进用药剂量低、治疗方案选择缺乏依据、给药途径与溶媒用量错误等不合理用药情况。     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Polymorphisms in genes involved in neurotransmission in relation to smoking

Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D₁, D₂, and D₄ receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D₃ and D₅ receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.     

Genotoxic effects of chlorophenoxy herbicide diclofop-methyl in mice in vivo and in human lymphocytes in vitro

Diclofop-methyl (DM) is a chlorophenoxy derivative used in large quantities for the control of annual grasses in grain and vegetable crops. In this study, the genotoxic effects of DM were investigated by measuring chromosomal aberrations (CAs) in mouse bone-marrow cells and CA and the comet assay in human peripheral lymphocytes. Mice were treated with 15.63, 31.25, 62.5, and 125?mg/kg body weight of DM intraperitoneally for 24 hours, and 15.63-, 31.25-, 62.5-, 125-, and 250-µg/mL concentrations were applied to human lymphocytes for both 24 and 48 hours. In in vivo treatments, DM significantly, but not dose dependently, increased the total chromosome aberrations, compared to both negative and solvent controls. Cell proliferation was significantly, but not dose dependently, affected by all doses. In in vitro treatments, DM (except 15.63 µg/mL) significantly and dose dependently increased the frequency of chromosome aberrations. Also, 250 µg/mL of 48-hour treatment was found to be toxic. Cell proliferation was significantly and dose dependently affected by DM applications, when compared to negative control. In in vitro treatments, DM significantly decreased the mitotic index only at the highest concentration for 24 hours, and 62.5- and 125-µg/mL concentrations for 48 hours. In the comet assay, a significant and dose-dependent increase in comet-tail intensity was observed at 62.5-, 125-, and 250-µg/mL concentrations. The mean comet-tail length was significantly increased in all concentrations. Our results demonstrate that DM is genotoxic in mammalian cells in vivo and in vitro.     

2010调脂治疗领域进展

2010年在调脂治疗领域针对他汀治疗心血管病的防治又进行了许多探索。本文通过综述他汀类药物的国际大规模临床试验结果,重新评价了他汀类药物在冠心病一级预防和冠心病二级预防中的地位,阐明了强化他汀治疗的意义;对他汀的心肾保护作用和安全性新证据进行了说明。     

Pradigastat disposition in humans: in vivo and in vitro investigations

1.?Pradigastat is a potent and specific diacylglycerol acyltransferase-1 (DGAT1) inhibitor effective in lowering postprandial triglycerides (TG) in healthy human subjects and fasting TG in familial chylomicronemia syndrome (FCS) patients.

2.?Here we present the results of human oral absorption, metabolism and excretion (AME), intravenous pharmacokinetic (PK), and in vitro studies which together provide an overall understanding of the disposition of pradigastat in humans.

3.?In human in vitro systems, pradigastat is metabolized slowly to a stable acyl glucuronide (M18.4), catalyzed mainly by UDP-glucuronosyltransferases (UGT) 1A1, UGT1A3 and UGT2B7. M18.4 was observed at very low levels in human plasma.

4.?In the human AME study, pradigastat was recovered in the feces as parent drug, confounding the assessment of pradigastat absorption and the important routes of elimination. However, considering pradigastat exposure after oral and intravenous dosing, this data suggests that pradigastat was completely bioavailable in the radiolabeled AME study and therefore completely absorbed.

5.?Pradigastat is eliminated very slowly into the feces, presumably via the bile. Renal excretion is negligible. Oxidative metabolism is minimal. The extent to which pradigastat is eliminated via metabolism to M18.4 could not be established from these studies due to the inherent instability of glucuronides in the gastrointestinal tract.