对我国药品定价引入经济性指标的思考

目的:为提高我国药品定价的科学性和合理性提供参考。方法:分析我国药品定价引入经济性指标方面的已有研究成果的合理性及存在的问题并提出较为合理的定价办法。结果:笔者认为合理的定价方法应为:首先,确定每一类治疗相同适应证下不同通用名药品中满足临床需要的最低价格品种为该类药品的代表品,然后以代表品的价格为基准,对待定价药品与代表品的功能进行倍比打分,以此作为分子,再将待定价药品的价格与代表品药品价格之比作分母,通过两者之比所得值对1的偏离程度,确定待定价药品应提价还是降价及价格涨落幅度。而代表品的定价可采用成本加成法确定。结论:本研究提出的方法可通过将定价目标与药品临床效果紧密结合实现价值定价,可科学、合理、经济、高效地同时满足药品定价目标及我国"批量式"定价的客观要求。     

英国药品定价方法的调整趋势及对我国的启示

目的:为我国政府部门制定和调整药品价格提供参考。方法:明晰英国药品定价的目标,分析其定价方法对定价目标的支撑和吻合情况,介绍和分析其新的调整趋势——价值定价法。结果与结论:英国药品定价方法在不断调整和完善,价值定价法更加符合价格管理目标的客观要求。我国政府定价部门应及早予以深入研究和尝试此类方法,通过对药品的成本-效果进行评估、确定药品间功能差异指标、确定指标权重、评价药品的价值,进行合理的药品定价。     

基于价值的药品价格制定与调整的路径研究

目的:为提高我国药品价格制定与调整方法的科学性、合理性提供参考。方法:明确药品价格管理的目标,进而判定现行的药品价格制定与调整方法对目标要求的实现度。结果:药品价格管理的目标应与药品管理的总目标相一致,即安全、有效、经济、适当。我国药品定价办法一直局限于药品加成定价的框架,且没能将药品价格管理总目标对各方面的要求予以综合地、系统地考虑和体现。本研究提出的方法主要通过不同药品间功能的倍比打分来实现基于药品价值的价格制定与调整路径。结论:该方法既能满足我国"批量化"进行的药品价格调整的需求,又能更好地实现药品价格管理目标。     

卫生技术评估在欧洲4国的应用及对我国的启示

目的为完善卫生技术评估(HTA)在我国医保药品决策中的应用提供参考。方法从HTA机构的设置、HTA的流程两个方面着手,对HTA在英国、法国、德国和瑞典医保药品决策中的应用进行梳理、分析,并结合我国HTA的实施情况提出完善建议。结果与结论英国、法国、德国和瑞典均设置了专门的HTA机构,机构间既各司其职又密切协作;在HTA的实施过程中,上述4个国家均设置了不同的价值评估标准去筛选具有“高性价比”的药品,利益相关方均积极参与,均将评估结果及决策公开,均设置了异议处理环节,均为提高药品可及性开设了快速评估通道,并且为保证医保可持续性均会对已纳入报销目录内的药品进行重新评估。建议我国结合国情,加强HTA机构间的合作及人才培养,综合评估药品价值,促进利益相关方参与,提高决策透明度,完善我国HTA的实施程序。     

我国医保药品支付价格政策改革探讨

目的:为我国政府制订医保药品支付价格提供政策建议。方法:阐述医保支付价格政策起源及其他国家实施该政策的效果和出现的问题,在我国新医改背景下结合理论分析及实证研究探讨医保药品支付价格定价机制。结果:药品支付价格政策改革将会对目前医药市场和医疗保险支付产生较大影响,对研发型制药企业的影响和冲击较大。该政策可节约医保资金中药品费用支出,对卫生总费用是否降低有待进一步探索和实践。结论:建议医保政策实施时注意相关配套措施改革。政府应在药品可获得性和鼓励药品研发创新性方面保持平衡。     

我国药品价格改革探析

目的探讨我国药品价格改革的思路、方法与成效。方法分析我国药品价格改革的特点、趋势及存在的问题,并参考国外药品价格改革的经验。结果与结论我国的药品价格改革以降价为主线,在一定程度上抑制了药品的虚高定价;药品定价更加趋于合理,包括合理升高普药的价格,定价程序更加规范以及行政定价转向专家定价等,但仍存在一些值得探讨的问题。     

印度药品价格管理制度及对我国的启示

目的:借鉴印度药品价格管理制度中适用于我国的做法。方法:根据文献分析印度药品价格控制的现状及制度,并且分析我国药品定价制度存在的缺陷。结果与结论:印度的药品价格管理制度对保持印度药品成本的竞争性起到了积极的作用,而我国的药品定价制度还有诸多不完善之处,有待于改进,应当成立专门的药品价格管理机构制定、审批、修改和监督药品价格。     

我国药品价格形成机制改革探讨

我国药品价格长期居高不下的成因涉及药品定价、生产、流通、消费、医院补偿机制等方面。政府抑制“药价虚高”的思路是放开药品经营;加快医疗保险和卫生体制改革;加大药品生产、流通体制改革的力度;加大药品定价的监管力度。     

药品单独定价机制的合理性研究

目的:分析我国目前药品单独定价机制的合理性。方法:比较筛选出的167种政府定价药品的单独定价价格和普通价格,统计、分析其价格差异。结果与结论:此次统计范围中,单独定价药品与普通药的价格差距大,约1/3的普通药品价格低于单独定价药品价格的50%;其中,有10个品种的单独定价药品价格高出普通药价格5倍以上;此外,单独定价的药品中,不同企业生产的相同剂型相同规格的同种药品价格差异也十分显著。因此,有必要深入研究药品价格,建立等效等价的药品价格定价机制,限制单独定价范围,完善药品价格监督制度。     

药品价格机制的探讨

药品属于商品范畴,其价格的制定应遵循商品价值的基本原则和市场规律。即要以社会平均成本为依据,反映市场供求状况,考虑社会承受能力等。我国施行政府对部分药品价格实行政府定价和政府指导价的管理形式。生产流通环节对药品价格的影响程度带来价格变动。西方国家药品政策,价格管制的形式：定价管制、比较定价、参考定价、利润控制与强制削价。我国的药品价格体系如何完善,让企业,药价与患者共同融入和谐圈。     

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.