用后效应理论分析抗菌药物给药方案

目的：本文通过对抗菌药物给药方案进行分析，探讨利用后效应理论指导临床合理用药的必要性。方法：运用后效应理论对不同抗菌药物给药方案进行回顾性分析评价。结果：全院抗菌药物使用率为54．5％。符合抗生素后效应给药方案占当日使用抗菌药物总例数的44．4％，不符合的占55．6％。结论：后效应理论在优化给药方案，为临床合理用药方面提供了循证依据。     

抗生素后效应在临床给药方案中的合理应用

抗生素后效应(PAE)的研究，给抗菌药物用药方案的合理制定提供了科学依据，PAE参数提供了更多药物、细菌与机体3者之间作用关系的信息。提示药物在血清和组织浓度低于MIC时仍可抑制细菌生长，使药物的有效性得以延长。临床可根据各类抗菌药PAE的长短，结合药动学参数，确定新的用药剂量、间隔时间和次数，优化给药方案。降低药物的毒副作用和医疗费用，提高抗菌药物的治疗水平。     

探讨抗菌药物后效应与临床合理使用抗菌药物

目的探讨抗菌药物后效应对于指导临床合理使用抗菌药物的重要作用。方法结合相关参考文献,对于各类抗菌药物后效应进行分析论证,进而给出合理的用药方案。结果抗菌药物后效应使药物低于MIC时仍可以持续发挥抑菌作用,有助于更好地确定用药剂量和间隔时间,制定合理给药方案。结论根据抗菌药物后效应制定临床合理的用药方案,对于提高抗菌药物的治疗水平,降低毒副作用,保证抗菌药物对细菌的敏感性,减少耐药现象具有非常重要的意义。     

常用抗菌药物的给药时间研究与临床合理用药

目的研究常用抗菌药物的给药时间及临床的合理用药,探索临床正确的用药方法。方法通过收集相关文献资料并进行整理,同时结合实际临床用药,根据临床常用药物的代谢动力学(PK)和效应动力学(PD)及药物后效应(PAE)的不同,回顾性的分析研究临床常用抗菌药物给药时间方法和合理用药方式。结果通过研究常用抗菌药物的最优给药时间及其联合用药的给药间隔,合适合理的用药时间及间隔能有效提高药物的疗效,知道临床合理用药。结论熟悉临床各种常用药物的给药时间及其给药间隔期,最佳化给药方案,提高药物疗效,促进患者康复。     

抗生素后效应在临床给药方案中的应用分析

临床合理用药的意义首先是提高疗效,其次是减少药源性危害.抗生素后效应(PAE)的研究,提供了机体、药物及细菌三者之间的关系信息,为临床给药提供了有力的理论依据与科学依据,抗生素后效应的研究显示药物在组织浓度低于平均抑菌浓度时仍可抑制细菌生长,从而延长了药物的有效性.因此,在临床指导用药时可根据各类抗菌药后效应,结合药代学与药动学参数,优化给药方案,确定新的给药间隔时间和用药次数、剂量.从而最大限度地发挥药物的效果,降低毒副作用与医疗费用,对合理使用抗生素具有积极的意义.     

抗生素后效应

目的：介绍各种抗生素的抗生素后效应，为临床给药间隔提供参考数据。方法：综述各种抗生素的抗生素后效应概况。结果：提供了各类常用抗生素和联合用药后效应的时间。结论：抗生素后效应为临床设计合理的给药方案提供科学依据，指导临床更合理地使用抗生素。     

抗生素后效应与合理使用抗生素

抗生素后效应(PAE)系指细菌与抗生素短暂接触,当药物浓度下降低于最低抑菌浓度(MIC)或消除后,细菌的生长仍受到持续抑制的效应.其临床的重要意义在于,以前设计抗生素给药方案仅依靠血药浓度、消除速率及组织分布等一些药代动力学数据作参考,忽视了药物对细菌生长繁殖规律的影响.而PAE理论指出,确定抗生素的给药间隔应根据药物浓度超过MIC或最低杀菌浓度的时间加上PAE的持续时间,从而可延长给药时间,减少药物剂量,起到既不影响疗效又可降低药物不良反应的作用.目前PAE已成为评价新的抗菌药物、设计合理给药方案的重要参考指标.     

根据抗菌药物后效应与合理用药

随着对抗菌药物后效应(PAE)研究的深入,发现多种抗菌药物都具有PAE。目前PAE已成为评价新的抗菌药物、设计合理给药方案的重要参考指标,广大的医药工作者对抗菌药物的作用机理更加重视。1抗菌素后效应的定义及意义抗菌素后效应(PAE)系指细菌与抗生素短暂接触后,在药物被清除的情况下,细菌生长仍受持续抑制的效应。许多抗生素的抗菌活性与药物的高峰浓度密切相关,有明显的剂量(浓度)依赖性,体内抗生素不必始终维持在有效血药浓度之上。在PAE期的细菌许多特征发生了改变,使得在治疗中可以延长给药时间,减少用药剂量,从而减少不良反应的…     

2008年1～5月我院门诊儿科抗生素不合理处方分析

目的：了解我院门诊儿科抗菌药物处方不合理用药情况。方法：随机抽取2008年1～5月儿科门诊处方,根据临床药理学及文献资料,对不合理的抗生素用药处方进行分析,并加以分类统计。结果：共审核处方20 936张,其中抗生素处方11 743张,存在不合理用药1 852张,分别在给药方案、药理作用、合并用药、重复用药、剂量不足以及使用不当等方面存在问题。结论：我院门诊儿科抗生素使用基本符合抗菌原则,但仍需进一步提高。     

抗生素后效应及其临床意义

抗生素后效应（Postantibioticeffect,PAE）是近年来在国外开始受到关注的新理论,它是抗菌药物对致病微生物所特有的反应,可为研究抗菌药物的药效动力学及临床给药方案的设计提供新的依据。抗生素后效应（PAE）系指细菌暴露于抗生素,在抗生素作用下被杀灭或被抑制,但当抗生素消除,其浓度下降到MIC以下,或降到可忽略不计时,细菌生长仍受到持续抑制的现象。本文就PAE的产生机制、不同抗生素的PAE特点、抗生素浓度对其的影响、合理给药方案的设计进行综述。1PAE的产生机制确切的机制尚不清楚,可能的机制有：（1）对细菌非致死…     

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.     

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 x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 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.     

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.     

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     

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。     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Trichinellosis in immigrants in Switzerland

We describe a case of trichinellosis diagnosed at the Division of Infectious Diseases, Hospital of Lugano, in January 2009. This case was associated with a cluster of cases and was traced to the consumption of contaminated meat after a wild boar hunt in Bosnia.