浅析如何提高药品靶向抽验水平

药品监督抽验是药品监督管理部门在药品监督管理工作中,为保证人民群众用药安全而对监督检查中发现的质量可疑药品所进行的有针对性的抽验,是食品药品监管部门在药品监督检查中加强药品质量监督的重要手段,也是发现假劣药品的重要途径之一。很多假劣药品的发现,均来源于药品监督抽验。但是在新的药品监管形势下,以往的药品监督抽验,已远远不能满足新时期药品监管工作的需要,必须开拓新思路,研究新技术,寻求新方法,初步实现"靶向抽验"的目的。     

2002-2007年北京市药品抽验情况调查

药品是防病治病的特殊商品。为保护人民健康，保证药品质量，我国对上市药品实行抽验制度。抽验制度是药品监管的一大法宝。各级药品监督部门都十分重视抽验工作，不断加大药品抽验力度。笔者对北京市2002～2007年的药品抽验情况进行了全面调查，力求全面反映北京市药品抽验工作的现状，以便为各级药检部门制定更科学合理的抽验计划和抽验方案，有效提高抽验工作的效能服务。     

1999、2000年药品抽验情况分析

药品抽验是药品质量监督的一个方面 ,通过抽验能够对药品的质量进行系统评价、及时发现存在的药品质量问题以及与药品质量有关的其他问题 ,是保证药品质量的重要手段之一。各级药品检验机构作为药品监督管理部门的技术依托单位 ,按照新修订的《药品管理法》承担药品监督检查中所需的检验工作 ,如何充分发挥药检机构的作用 ,调动其积极性和主观能动性是做好抽验工作的关键所在。下面就 1999年、 2 0 0 0年抽验工作的一些具体情况作一分析。1　计划抽验计划抽验包括国家级和省级 ,这里只谈国家计划抽验。计划抽验又分为统一抽验和专项抽验。1 …     

改革药品抽验机制提高药品抽验效能

药品抽验是药品质量监督的重要手段,是药品稽查工作的技术支撑,是保证人民群众用药安全有效的重要举措.为此,国家每年都要投入大量的人力、财力保障抽验工作的顺利开展.但是,盲目抽验不仅造成抽验经费的浪费,给被抽验单位造成不必要的损失,还可能导致假劣药品＂漏网＂.为了解我市药品抽验工作开展情况,提高药品抽验效能,实现科学监管的工作目标,我局对全市药品抽验工作进行了调研,现将有关情况报告如下：     

药品监督抽验合格率与药品质量(Ⅰ)

药品质量监督抽验是国家对药品实行监督管理的重要手段之一,是<药品管理法>赋予药品监督管理部门的重要职能.药品的特殊性决定了药品质量监督抽验的专业性、技术性和法定性.药品抽验按其功能划分有评价性抽验、日常监督抽验、专项监督抽验、跟踪监督抽验;按其行为划分,有计划抽验、检查抽验.无论哪种分类,都强调抽验计划的合理性、抽样程序的规范性、抽取样品的代表性、检验技术的可靠性以及抽验结果统计分析的科学性.作为衡量和评价药品质量状况与动态的重要指标-药品质量监督抽验合格率(以下简称合格率),正是在历经具有上述特性的实际操作步骤之后悄然而生的.由此不难看出合格率在药品质量监督抽验工作乃至整个药品监督管理体系中的重要地位.     

2002-2003年无锡市药品抽验情况分析

药品抽验是药品技术监督的重要组成部分，它对促进药品质量提高、保证人民用药安全有效，具有重大的意义。通过抽验能够对药品的质量进行系统评价、及时发现存在的质量问题以及与质量有关的其它问题，因此药品抽验是保证药品质量的重要手段之一。     

欧盟药品上市后抽验模式分析与启示

由于我国药品生产企业数目众多,流通环节众多,市场保障体系建立尚不完全,因而影响药品安全的风险因素也较多,药品质量问题越来越引起了国家与公众的重视。与我国相比,欧盟已经建立了完善的药品抽验体系,本文通过对欧盟上市后药品抽验监管机构及技术机构的介绍,并对集中抽验和市场监督抽验两种模式进行研究,为我国上市后药品的评价性抽验和市场监督抽验提供借鉴。     

我国药品质量监督抽验情况分析及建议

目的：为完善我国药品监督抽验管理,提高我国药品监督抽验水平提供参考。方法：基于对我国现行药品抽验管理相关规定的了解,通过对国家食品药品监督管理总局（CFDA）2011-2014年公布的药品质量公告中相关数据进行统计分析,采用逻辑推理的方法对目前我国药品监督抽验存在的问题进行探讨。结果与结论：目前,我国药品监督抽验存在过于偏重国家基本药物、资源浪费、监管力量相对不足、检验技术未能有效发挥技术支撑作用等问题。建议通过合理制订抽验计划、改善抽验模式以及使用新兴药品监管技术,缓解目前我国药品监管中存在的问题。     

贵州省黔南州2002-2005年药品抽验情况分析

药品抽验工作是药品技术监督的重要组成部分,各级药品监督部门都十分重视,不断加大药品抽验力度,促进了药品质量的提高。本文对贵州省黔南州2002～2005年药品抽验情况进行了统计分析,以全面反映黔南州药品抽验工作的现状,更好地制定合理的抽验计划,提高技术监督效能。抽验总体合格率呈上升趋势2002～2005年该州药检所共计完成辖区内抽验检品2374批,不合格220批,不合格率为9.3%,详见附表1。从附表1看出,抽验药品的合格率从2002年的85.9%上升到2005年的93.4%,说明几年来药品监督管理部门加大了对药品的监管力度,全州药品质量呈上升趋势,但抽验…     

军队药品质量监督抽样的特殊性探讨

国家对药品质量实行监督抽验,是促进药品质量提高,保证人民用药安全有效的重要手段之一,而药品抽样是药品抽验工作的主要组成部分。笔者在部队药品检验所从事多年的药品监督抽样工作,通     

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.