注射剂原研药与仿制药的政府定价比较

目的:为完善药品政府定价,特别是对于原研药的定价提供参考。方法:通过统计国家发改委药品定价目录中的价格数据,计算注射剂中原研药与仿制药价格的差价率。结果:满足《药品政府定价办法》中对于差价率规定(注射剂差价率35%)的药品仅占总数的26%,且最高的一个差价率超过500%。结论:建议政府采用逐步降价等较温和方法,控制给予原研药的价格优惠程度,并建立动态的价格调控机制,使原研药生产企业与仿制药生产企业利益趋于平衡。     

原研药与仿制药的药品最高零售限价与药品集中招标采购中标价的差异比较

目的:为深化我国药品价格改革提供参考。方法:通过纳入的抗微生物药物和循环系统药物(94个品规),计算我国2005-2013年原研药与仿制药最高零售限价和药品集中招标采购中标价差率。结果:仿制药最高零售限价与中标价差异大,而原研药最高零售限价与中标价则较为接近。就仿制药而言,抗微生物药的最高零售限价与中标价差率明显高于循环系统药;而就原研药而言,抗微生物药的最高零售限价与中标价差率接近循环系统药。结论:药品最高零售限价与药品集中招标采购中标价并存的格局应逐步转型为以药品集中招标采购中标价为基础的格局。     

基于WHO/HAI标准化法的山东省50种药品价格及可获得性研究

摘要：目的:分析山东省药品在公立医院和零售药店药品的价格和可获得性情况,为药品政策研究提供数据支持。方法:应用世界卫生组织和健康行动国际组织共同制定的标准化法,于2018年对山东省6个市的47家公立医院和46家零售药店的50种药品的价格和可获得性进行调研,并与国际药品参考价格进行对比分析,评价药物的可负担性。结果:原研药和最低价格仿制药在公立医院的可获得性分别为10.3%和32.4%,在零售药店的可获得性分别为和13.7%和32.3%。原研药和最低价格仿制药在公立医院的中位中位价格比分别为8.44和1.96,在零售药店分别为7.77和2.97。原研药和最低价格仿制药可负担性较好的品种数占比在公立医院分别为28.57%和81.82%,在零售药店分别为33.33%和77.78%。结论:原研药的可获得性低,最低价格仿制药的可获得性一般;原研药价格远高于国际参考价;公立医院的药品价格低于零售药店;原研药的可负担性一般,最低价格仿制药的可负担性较好。     

仿制药替代潜在最大费用节省研究

目的在仿制药替代背景下,比较原研药和仿制药的价格和采购量,测算仿制药替代的潜在最大费用节省,推动仿制药供应与使用。方法基于陕西省药品招标采购数据,选取2017年12月第一批通过仿制药质量和疗效一致性评价的17个品种(16个品规)药品,对其2017年至2018年的价格、采购量进行分析;采用成本分析法、推测预算法,对采购平台上该通用名、剂型的药品替换为通过仿制药质量和疗效一致性评价单价最低的仿制药,测算年均仿制药替代的潜在最大费用节省。结果价格由高到低依次为原研药、未通过一致性评价的仿制药、通过一致性评价的仿制药;采购量方面,5个品规药品的原研药采购量占比较高,11个品规药品的仿制药采购量占比较高,1个品规药品未发生仿制药替代;对16个品规药品进行仿制药替代后,测算出潜在最大费用节省为3243.63万元。结论仿制药替代可显著节省药品费用,我国的仿制药市场提升空间较大,后续应加快推进仿制药一致性评价和临床使用。     

江苏省某三级公立医院治疗高血压和糖尿病的原研药和仿制药利用分析

目的:为仿制药替代原研药的经济效益提供证据支持,提出促进仿制药使用的政策建议。方法:选取江苏省某三级公立医院治疗高血压和糖尿病的12种既有原研药又有仿制药的药物,逐季度分析2017-2018年原研药和仿制药使用量占比、使用金额占比、价格比和2018年仿制药替代原研药的潜在费用节省率。结果:2017年第1季度-2018年第4季度,原研药、仿制药使用数量占比分别由24.53%上升至39.12%、75.47%下降至60.88%,使用金额占比分别由39.45%上升至61.47%、60.55%下降至38.53%,仿制药与原研药价格比从0.50下降到0.40。在疗效一致的条件下,2018年仿制药替代原研药潜在可节约费用62.21万元,费用节省率为47.65%。结论:仿制药替代原研药具有降低药品支出的作用,但该院仿制药使用或金额占比却逐渐下降。因此,有必要加快仿制药一致性评价的进程及临床等效研究,加大仿制药处方及合理使用的教育宣传,以提高医患对仿制药质量和疗效的认同,配合鼓励仿制药采购及使用的集中采购政策,促进仿制药利用以节约药品支出。     

专利到期对药品价格和市场份额的影响分析

目的:系统评估国内外药品专利到期后价格及市场份额的变化,为促进我国创新药与仿制药的平衡发展提供循证参考.方法:计算机检索PubMed,Scopus,The Cochrane Library,CNKI,WanFang Data和VIP数据库,搜索与专利到期或专利过期对原研药或仿制药价格及市场份额影响有关的研究,检索时限为...     

我国仿制药上市对原研药价格的影响

许多国家广泛鼓励仿制药上市,它已成为降低药品价格的有效方法.我国是仿制药大国,不但仿制的品种多,而且单个品种的生产企业也多.本文通过分析我国仿制药与原研药现行最高零售价与仿制药企业数量的关系,试图对政府定价方法提出合理性建议.     

陕西省公立医院和零售药店基本药物价格及可获得性比较研究

目的:比较陕西省公立医院和零售药店基本药物的价格及可获得性状况,为国家基本药物制度的顺利推行提供实证支持和对策建议。方法:采用世界卫生组织(WHO)和世界健康行动组织(HAI)共同制定的WHO/HAI调研手册,利用其中的标准化调研方法对120家公立医院和120家零售药店的38种基本药物进行调研。结果与结论:公立医院和零售药店的基本药物可获得性存在差异,原研药的零售价远远超过国际参考价,最低价格仿制药的零售价相对合理,公立医院和零售药店基本药物的可负担性情况基本一致。零售药店的平均可获得性均高于公立医院;零售药店和公立医院基本药物的可获得性高低分布基本一致;无论在公立医院还是在零售药店,原研药的零售价均较高,最低价格仿制药的零售价相对合理;公立医院原研药的中位价格比(MPR)值高于零售药店,最低价格仿制药的中位MPR值低于零售药店;无论在公立医院还是在零售药店,原研药的可负担性均较差,最低价格仿制药的可负担性均良好。结论:加强国家基本药物制度的宣传力度,制定合理的基本药物补贴、采购机制和价格,加强政府监管,是实现国家基本药物制度健康、顺利推进的必要措施。     

基于WHO/HAI标准化法的陕西省公立医院儿童基本药物可获得性及价格研究

目的:为我国儿童基本药物目录的出台及改善儿童基本药物的使用现状提供参考。方法:采用世界卫生组织/国际健康行动组织共同制定的WHO/HAI标准化法,于2012年对陕西省6个城市的60家公立医院的28种儿童基本药物进行调研,将公立医院药品的采购价格和零售价格与国际参考价进行对比研究。结果:儿童基本药物在公立医院的可获得性低;原研药的采购价格和零售价格远高于国际参考价,最低价格仿制药的采购价和零售价相对较低;原研药和最低价格仿制药的可负担性较好。结论:应尽快出台儿童基本药物目录;制药企业应加大研发适宜儿童使用的药物剂型、规格及包装;公立医院药品采购应兼顾儿童用药。     

中国与西太平洋地区发展中国家公立药品采购系统基本药物价格比较及启示

目的:为制定和调整我国基本药物价格和采购监管政策提供参考。方法:对我国黑龙江省、马来西亚、蒙古和越南的公立药品采购系统相关政策,及其2009年5～9月31个基本药物的公立采购价格进行国家间和与国际及世界卫生组织西太平洋地区中位数价格的比较、分析。结果与结论:我国黑龙江省公立药品采购系统多数只采购国产通用名药,价格水平与健康管理科学组织(MSH)和世界卫生组织西太平洋地区相当,但与印度通用名药、甚至是品牌通用名药相比偏高。某些同时采购通用名药和原研药的品种价差与他国相比过大,但一些原研药仍能在公立药品采购系统中有一席之地。原研药和通用名药"共生"的品种,价格与印度相比没有优势,国产通用名药的价格甚至高于印度品牌通用名药。     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Arsenic induced changes in growth development and apoptosis in neonatal and adult brain cells in vivo and in tissue culture

Arsenic at a nonlethal level in drinking water consumed over a period of time has been reported to produce chronic toxicity and various types of health problems ranging from skin cancer to disturbance in memory. Neurotoxic effects have been reported in clinical cases with chronic exposure to arsenic. Physiological detoxication of arsenic occurs partially through methylation. Arsenic and its methylated derivatives are distributed in different organs and systems. The present study examined the possible interference in the neuronal development and differentiation due to the exposure to arsenic during gestation. The experiments were carried out to examine short and long term effects of arsenic on brain explants and cells grown and maintained in tissue culture system. The effects of arsenic exposure showed changes in brain cell membrane function indicated by generation and release of reactive oxygen-nitrogen intermediates. On the morphological aspect the explants' growth was reduced, ground matrix was lost and neural networking was inhibited. Cells showed signs of apoptotic changes. Arsenic toxicity may induce damage to brain cells prior to more visible clinical conditions. The deleterious effects also pass from the maternal to fetal tissue across the transplacental barrier.     

Nicotine metabolism and urinary elimination in mouse: in vitro and in vivo

This study aimed at elucidating the in vivo metabolism of nicotine both with and without inhibitors of nicotine metabolism. Second, the role of mouse CYP2A5 in nicotine oxidation in vitro was studied as such information is needed to assess whether the mouse is a suitable model for studying chemical inhibitors of the human CYP2A6. The oxidation of nicotine to cotinine was measured and the ability of various inhibitors to modify this reaction was determined. Nicotine and various inhibitors were co-administered to CD2F1 mice, and nicotine and urinary levels of nicotine and four metabolites were determined. In mouse liver microsomes anti-CYP2A5 antibody and known chemical inhibitors of the CYP2A5 enzyme blocked cotinine formation by 85–100%, depending on the pre-treatment of the mice. The amount of trans-3-hydroxycotine was five times higher than cotinine N-oxide, and ten times higher than nicotine N-1-oxide and cotinine. Methoxsalen, an irreversible inhibitor of CYP2A5, significantly reduced the metabolic elimination of nicotine in vivo, but the reversible inhibitors had no effect. It is concluded that the metabolism of nicotine in mouse is very similar to that in man and, therefore, that the mouse is a suitable model for testing novel chemical inhibitors of human CYP2A6.     

Circulating nucleic acids in plasma and serum: roles in diagnosis and prognosis in diabetes and cancer

The presence of DNA and RNA circulating in human plasma and serum is described. The possible sources of the DNA/RNA in blood, their ability to enter other cells and to express in the recipient cells are discussed and the relationship with metastases considered. The possible role(s) of the DNA/RNA in clinical diagnosis, in monitoring treatment and in prognosis are considered for diabetes and oncology.     

SalB stimulates neurogenesis and angiogenesis in vitro and in vivo

Aims： Previous studies suggested that Salvianolic acid B （SalB） has strong protective effect against cerebral ischemia. Recently, Sal B has been reported to enhance angiogenesis in vitro. Based on the information above, in this study we are interested in the effect of SalB on neurogenesis and angiogenesis. Methods：In vitro study, we used embryonic mouse （El6） primary cortical neural cultures. Neuron was recognized by anti-MAP2 with immunocytochemistry. Neurogenesis was tested with BrdU incorporation by ELSA method. SalB（ 10 -6 -10 -8M） or vehicle was added to the culture medium 24 hrs before BrdU addition. In vivo, middle cerebral artery occlusion （MCAO） rats were used as focal cerebral ischemia model.     

Metabolic interaction between imipramine and carbamazepine in vivo and in vitro in rats

Summary The pharmacokinetic consequences of the combination of carbamazepine with imipramine in male Wistar rats have been investigated. It was found that a 2-week treatment with the combination resulted in the increase of the concentrations of the parent compounds and a simultaneous decrease in their metabolites in blood plasma i.e. carbamazepine inhibited imipramine demethylation in the side chain while imipramine inhibited carbamazepine 10,11-epoxidation. The velocity of imipramine 2-hydroxylation and 10,11-epoxy-carbamazepine hydration did not seem to be changed by the combination. On the basis of studies in vitro it is concluded that the observed metabolic interaction between carbamazepine and imipramine is due to the competition of the drugs for the active centre of cytochrome P 450 and to a certain qualitative alteration of the enzyme by imipramine as can be deducted from the decrease of carbamazepine binding to the cytochrome. Send offprint requests to K. J. Netter     

Nicotine metabolism and urinary elimination in mouse: in vitro and in vivo

This study aimed at elucidating the in vivo metabolism of nicotine both with and without inhibitors of nicotine metabolism. Second, the role of mouse CYP2A5 in nicotine oxidation in vitro was studied as such information is needed to assess whether the mouse is a suitable model for studying chemical inhibitors of the human CYP2A6. The oxidation of nicotine to cotinine was measured and the ability of various inhibitors to modify this reaction was determined. Nicotine and various inhibitors were co-administered to CD2F1 mice, and nicotine and urinary levels of nicotine and four metabolites were determined. In mouse liver microsomes anti-CYP2A5 antibody and known chemical inhibitors of the CYP2A5 enzyme blocked cotinine formation by 85-100%, depending on the pre-treatment of the mice. The amount of trans-3-hydroxycotine was five times higher than cotinine N-oxide, and ten times higher than nicotine N-1-oxide and cotinine. Methoxsalen, an irreversible inhibitor of CYP2A5, significantly reduced the metabolic elimination of nicotine in vivo, but the reversible inhibitors had no effect. It is concluded that the metabolism of nicotine in mouse is very similar to that in man and, therefore, that the mouse is a suitable model for testing novel chemical inhibitors of human CYP2A6.     

Pharmacokinetic and pharmacogenetic determinants and considerations in chemotherapy selection and dosing in infants

INTRODUCTION: There is a lack of high-quality data regarding optimal chemotherapy dosage regimens among infants. Dosing regimens for chemotherapy during the first year of life are commonly based on empiric recommendations extrapolated from older children; however, balancing efficacy and toxicity is critical as severe adverse drug reactions may lead to treatment failure or reduced adherence to needed medications. AREAS COVERED: This review describes pharmacokinetic and pharmacogenetic considerations when administering chemotherapeutic agents to infants. Examples of commonly used agents are provided with practical recommendations for dosing adjustments. EXPERT OPINION: Optimal chemotherapy for children and infants in particular has lagged behind the remarkable progress in cancer treatment and it is clear that far more basic and clinical research are needed with respect to the mechanistic basis of age-dependent differences in pharmacokinetic parameters. More recent studies which have combined pharmacokinetic data with clinical toxicity and outcome data have resulted in a number of more evidence-based guidelines at least for the initial chemotherapy dosing; however, at present, the dosing of chemotherapy drugs in neonates and infants remains largely empiric.     

Consistency in catecholamine and cortisol excretion in males and females

Data from a series of experiments performed on 24 female and 24 male subjects were used to evaluate the consistency in urinary catecholamine and cortisol excretion. Data were available from 8 laboratory situations of varying activity level and content, spaced at intervals of maximum 3 months. Correlational analyses showed that for cortisol, interindividual consistency was higher for measures obtained on the same day than for measures obtained on different days. Interindividual consistency was generally high in catecholamine and cortisol excretion during non-stressful situations in both sexes. During experimental stress, however, consistency was as high as during nonstress for males, while it was lower for females. Analysis of variance components confirmed these results and showed that in males variation due to interindividual differences was high during both baseline and experimental-stress situations, while in females it was high during baseline situations only. During experimental stress, variation for females was due primarily to interaction. It is suggested that the males showed a more generalized stress response over situations than the females.     

Penetration and action of edoxudine in vitro and in vivo

The penetration of 5-ethyl-2'-deoxyuridine (edoxudine, Aedurid) from gel base with and without the addition of urea and other adjuvant has been studied in an in vitro model using guinea pig skin. The formulation of 3% edoxudine gel with 5% urea showed the best results. In vivo experiments on hairless mice infected intracutaneously with herpes simplex virus type 1 also showed this formulation's good efficacy as compared to other formulations.