“问题药店”路在何方（上）

现在药店业进入到新一轮的运营管理时代，无论是超市化还是多元化、专业化都不可避免地有这样那样的问题，笔者称之为“问题店”。问题店不一定是最差的店，凡是药店自然就会存在一些问题，而作为一个药店经营管理者从哪里入手对药店经营进行检讨呢？药店经营须从营业绩效、来客数、客品数、品单价、毛利率、费用方面进行分析，从这几个方面着手经营检讨，找出属于自己薄弱的环节，持续改善药店经营，以精细化管理，促进药店经营业绩持续增长。     

理疗器械类：小品类的潜力

作为零售药店所经营的传统品类之一，器械类产品在药店的经营一直不温不火，所占份额也并不大。但是随着自我保健、自助理疗观念的深入人心，从中细化而生的用于家庭保健理疗的器械类产品开始逐渐旺销，成为零售药店大可挖掘的利润源之一。 为了了解全国各地不同药店对此类产品的经营状况，《中国药店》对全国主要大中城市的店员、柜台组长、店长、执业药师等药店工作人员进行了调查。     

厦门放宽连锁药店经营条件

厦门市将在全省率先开展调整药品零售连锁经营条件试点,关于连锁药店经营的硬性条件有所放宽。调整主要涉及两个方面。此前的规定是零售连锁总部仓库面积必须达到500平方米,调整后,要求零售连锁总部仓库面积大于300平方米。厦门市现有零售药店844家,但其中零售连锁门店仅有107家,占12．7％,具有较高知名度和美誉度、门店较多的连锁品牌还很少。     

鼓励连锁经营施行动态监管北京市平谷区药品市场监管经验二三谈

近年来,京郊地区零售药店呈现"小"、"散"、"多"的特点;在一些小药店中,各类"假药师"悄悄上岗;城乡药店经营管理水平差异明显……这些现象如不及时整顿治理,将会对百姓用药安全造成威胁.如何确保药店经营秩序?如何利用有限的监管资源有的放矢地对药店进行监管?如何加强企业的自律意识,自觉守法经营?笔者就北京市药品监督管理局平谷分局的监管新作法,新思路进行了探讨和分析.     

非药品经营抬级而上

2008年底，关于药店是不是应该偏离主业经营非药品的争论，一改过往各执一词的状态，零售药店的立场突然开始一边倒，许多尚未涉足非药品经营的企业开始跃跃欲试，而在该领域已小有所成的连锁药店更是将非药品的扩展列入了新的年度战略规划中。非药品，俨然成了2009年医药零售业的热门品类，成为新政策下出路探索的关键词之一。     

浅谈零售药店新人员岗前培训

零售药店小、散、多的现状，导致经营艰难，微利生存已实属不易，所以药店从业人员流动性较大，不断地招聘新人员成为较多零售药店的工作常态。为使新人员尽快进入工作状态，适应工作岗位，新人员上岗前的培训工作就显得尤为重要。现就新人员上岗前必须培训的内容简要介绍如下：     

Albertson''''s:称雄区域市场

在美国的众多连锁药店中Albertson's算是比较特别的一个,处方药的年销售额只占集团总销售额的15％。这是因为除了经营药店之外,Albertson's集团还以不同的品牌经营有多家食品杂货店,2002年集团的销售总额高达356亿美元。为了充分利用集团所拥有的各种资源,从2001年开始集团进行了大规模的重组,到2002年底为止集团一共关闭了224家杂货店和54家独立式药店,新开31家药店和61家杂货店,并对181家杂货店进行了装修改造。     

母婴品类生意缘何不温不火

随着政策的利好与药店多元化转型的深入，连锁药店企业在多元化经营的方向和产品需求方面也有了新变化，纷纷涉人母婴及药妆产品已成为药店未来发展的方向和趋势，但整个看来，目前成功的个案并不多，销售的业绩也不尽人意，原因何在？这是连锁药店管理者及销售人员一直想要知道的答案。     

基层零售药店GSP认证后的现状调查与研究

实施GSP认证是国家依法对药品经营企业进行监督检查并取得认可的一种制度；是通过强制性的认证建立质量管理体系，提高全员质量意识的过程。经过GSP认证，企业面貌焕然一新，经营设施齐备，店堂环境优雅，管理有章可循，工作井然有序，服务质量、管理理念、员工素质明显提高。 截止2004年底，我县123家零售药店全部通过了GSP认证，这一成果来之不易。为了进一步巩固GSP认证成果，规范药品经营市场，从2005年4月至5月，我们利用一个多月的时间，分成3组，对59家零售药店（其中单体零售药店36家，连锁公司加盟店23家）进行抽样调查。重点调研各零售药店是否严格按照GSP规范经营药品。调查中发现，大部分零售药店质量管理比较规范，但部分企业在质量管理上出现了回潮与反弹。     

开药店

无锡增加药店审批透明度 江苏省无锡市药品监督管理局近日公布了该局制定的《核发〈药品经营许可证〉(零售)工作程序》、《新设置零售药店申请立项须知》和《新设置零售药店现场验收须     

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     

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.     

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.     

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.     

Buprenorphine and naloxone alone and in combination in opioid-dependent humans

Subjective, physiological and behavioral effects of subcutaneously administered hydromorphone (6 mg), naloxone (0.2 mg), buprenorphine (0.2 and 0.3 mg), and two buprenorphine-naloxone combinations (buprenorphine 0.2 mg plus naloxone 0.2 mg and buprenorphine 0.3 mg plus naloxone 0.2 mg) were assessed under double-blind conditions in six opioid-dependent volunteers. Physiologic measures and subject- and observer-rated behavioral responses were measured before dosing and for 120 min after drug administration. Hydromorphone decreased pupil diameter and respiration, increased blood pressure and increased scores on subjective measures indicating opioid-like effects. Buprenorphine given alone had no significant effect on any variable measured. Naloxone given alone produced opioid abstinence-like effects which were measurable on subject- and observer-rated behavioral measures and physiological measures. Buprenorphine in combination with naloxone somewhat attenuated the naloxone-precipitated withdrawal response. Overall, the naloxone-buprenorphine combinations produced effects which were qualitatively similar to the effects of naloxone alone, suggesting a low potential for abuse of the combination product by opioid-dependent individuals.Supported by a grant from Reckitt and Colman Pharmaceutical Division and USPHS Grants DA-00050 and DA-04089 from the National Institute on Drug Abuse     

Cadmium in milk and mammary gland in rats and mice

The purpose of the present investigation was to study the uptake of cadmium in mammary tissue, effects on milk secretion and composition, and lactational transport of cadmium to the sucklings. Cadmium exposure during lactation resulted in retention of cadmium in the mammary tissue in mice and rats. The uptake of cadmium in the mammary tissue was rapid, as shown in lactating mice by whole-body autoradiography 4 h after an intravenous injection of a tracer dose of (109)CdCl(2). Retention of cadmium in kidneys of suckling pups was observed in the autoradiograms at 7 days after exposure of the dams. Lactating rats were intravenously infused with (109)CdCl(2) in 0.9% saline via osmotic minipumps from day 3 to day 16 after parturition. The cadmium dose given was 0, 8.8, 62 and 300 microg Cd/kg body wt. per day. Plasma and milk were collected at day 10 and 16 after parturition. Plasma cadmium levels in dams increased from day 10 to day 16. Cadmium levels were higher in milk than in plasma, with milk/plasma ratios varying from 2 to 6. Zinc levels in milk were positively correlated to cadmium levels in milk (r(2)=0.26; P=0. 03). In milk, (109)Cd was distributed in fat (46-52%), casein fraction (40-46%), and whey fraction (6-8%). There was a high correlation between cadmium concentrations in pups' kidney and cadmium concentrations in dam's milk (r(2)=0.98; P < 0.001). Of the cadmium dose given to the dams <0.05% was retained in the litters on day 16 of lactation. No effects were observed due to cadmium exposure on body weight in pups or dams. Cadmium treatment did not cause any effect on the lactose or protein concentration in milk, the concentrations of DNA, RNA or the ratio RNA/DNA in the mammary gland. Histological evaluation of mammary tissue did not reveal any abnormalities at any dose level. (109)Cd was bound to metallothionein in mammary tissue. The fraction of radiolabelled cadmium bound to metallothionein increased in a dose-dependent manner in both the liver (88-98%) and mammary tissue (57-80%). The present results indicate a low transfer of cadmium to the suckling pup, which might be due to binding of cadmium to metallothionein in the mammary tissue. However, during the susceptible developmental period even a low cadmium exposure may be of concern.     

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.