克拉维酸钾／阿莫西林片剂人体生物等效性研究

16名男性健康受试者分别随机交叉口服625mg克拉维酸钾/阿莫西林片(内含阿莫西林500mg,克拉维酸125mg)和进口阿莫克拉片(内含阿莫西林500mg,克拉维酸125mg),用微生物法测定血清中具有抗菌活性的阿莫西林的浓度,计算克拉维酸钾/阿莫西林片中阿莫西林的相对生物利用度。结果表明,阿莫西林在克拉维酸钾/阿莫西林片和进口阿莫克拉片的达峰时间Tmax分别为(1.688±0.814)、(1.250±0.465)h;达峰浓度Cmax分别为(9.332±2.238)、(9.289±2.089)mg/L;消除半衰期T1/2分别为(1.155±0.313)、(1.129±0.322)h;药-时曲线下面积AUC分别为(24.494±5.099)、(24.360±5.430)mg*h/L。两种制剂的主要药代动力学参数AUC及Cmax经方差分析无显著性差异(P>0.05)。克拉维酸钾/阿莫西林片的相对生物利用度为(101.6±13.8)%。对AUC进行双单侧t检验及90%可信限证实两种制剂生物等效。     

阿莫西林／克拉维酸钾片在健康人体的药代动力学与药效学

目的：探讨阿莫西林/克拉维酸钾片在健康人体的药代动力学与药效学。方法选取健康志愿者（男性）20名,给予阿莫西林/克拉维酸钾片625mg单次口服后,应用微生物法测定志愿者的尿药浓度、血药浓度。结果阿莫西林标准品与阿莫西林/克拉维酸钾片中的阿莫西林浓度一致;甲氧西林敏感金黄色葡萄球菌（ MSSA）、肺炎链球菌的MIC90的T＞MIC（％）46．7％;粪肠球菌、表皮葡萄球菌、嗜血流感杆菌的T＞MIC（％）均为38．3％;化脓性链球菌、卡拉莫拉菌的T＞MIC（％）均为66．7％。结论对于因肺炎链球菌、MSSA等常见致病菌引起的呼吸道感染疾病,应用阿莫西林/克拉维酸钾片（625mg/次,每天2次）进行治疗,具有较好的疗效。     

阿莫西林和克拉维酸钾复合制剂的药物动力学

本文对阿莫西林－克拉维酸钾复合制剂在９名健康成人中进行药物代谢动力学和生物利用度研究。血浆中药物浓度分别用藤黄八叠球菌和克雷伯氏肺炎杆菌为检定菌（用井式琼脂平板法）测定阿莫西林和克拉维田钾。单剂量口服２５０ｍｇ阿莫西林和１２５ｍｇ克拉维酸钾后其阿莫西林的Ｔｍａｘ１．１７±０．３１ｈｆｏ０．９７±０．３３ｈ；Ｃｍａｘ３．５±０．６μｇ／ｍｌ和３．６±０．７μｇｍｌ；Ｔ１／２１．１±０．３ｈ和１．１５±０．２７ｈ。克拉维酸钾为：Ｔｍａｘ１．ｌｌ±０．２４ｈ和０．８９±０．２９ｈ；Ｃｍａｘ３．６±１．０μｇ／ｍｌ和４．０±１．４４μｇ／ｍｌ；Ｔ１／２０．７８±０．１９ｈ和０．８±０．４ｈ。颗粒剂的相对生物利用度阿莫西林为１０４±２０％，克拉维酸钾为１０８±１１％。     

贵阳市医疗单位药品联合招标的72种抗生素中标零售价格

编号 品名氨节西林胶囊阿莫西林/克拉维酸钾粉针氨节西林/舒巴坦钠粉粉针氨节西林/舒巴坦钠粉粉针阿莫西林胶囊阿莫西林胶墨阿莫西林/克拉维酸钾片阿莫西林/克拉维酸钾片阿莫西林/克拉维酸咀嚼片阿莫西林/克拉维酸颖粒阿莫西林分散片阿莫西林颗粒阿莫西林颗粒阿莫西林粉针阿莫西林钠粉针阿莫西林钠粉针阿莫西林/舒巴坦钠粉针阿奠西林/克拉维酸钾针青霉素V片氨节青霉素胶囊氨节青霉素厂舒巴址纬内粉针呱拉西林钠粉针派拉西林钠粉针-美洛西林钠粉针美洛西林钠_氨氯青霉素针-苯哇青萄案针头泡曲松钠粉针头抱曲松钠粉针头抱噬月弓钠粉针头袍唾…     

2004年上半年录入ADR报表汇总分析

2004年上半年共录入ADR报表1289份,现汇总分析如下:序号12345678910111213141516通用名称注射用青霉素钠阿莫西林胶囊(阿莫仙)注射用氯唑西林钠注射用青霉素钾注射用哌拉西林钠注射用阿莫西林-克拉维酸钾注射用氨苄西林钠注射用青霉素钠注射用阿莫西林-克拉维酸钾(复方阿莫西林)注射用青霉素钠注射用舒他西林注射用舒他西林(舒氨新)阿莫西林颗粒剂(阿莫仙)阿莫西林颗粒剂(再林)阿莫西林-克拉维酸钾片(安灭菌片)阿莫西林-克拉维酸钾片(强力阿莫仙)用药途径静脉滴注口服静脉滴注静脉滴注静脉滴注静脉滴注静脉滴注肌内注射静脉滴注静脉注射静…     

反相高效液相色谱法检测阿莫西林-克拉维酸钾（8∶1）干混悬剂血药浓度及生物等效性研究

目的采用反相高效液相色谱法测定阿莫西林-克拉维酸钾（8∶1）干混悬剂在健康志愿者体内的血药浓度,并研究其相对生物利用度。方法20名男性健康受试者采用双周期自身对照交叉试验,分别服用阿莫西林-克拉维酸钾（8∶1）干混悬剂和阿莫西林-克拉维酸钾（8∶1）片剂。采用RP-HPLC法分别测定血浆中克拉维酸钾和阿莫西林的浓度,使用DAS软件计算克拉维酸钾和阿莫西林的药物动力学参数与干混悬剂的相对生物利用度。结果阿莫西林和克拉维酸的线性范围分别为0.5-40、0.05-5μg.mL-1,提取回收率均〉75%。单剂量口服参比制剂和受试制剂后,阿莫西林和克拉维酸钾的药动学参数如下：t1/2分别为（1.64±0.72）、（1.80±1.05）h和（1.90±0.84）、（2.12±1.35）h;Cmax分别为（13.19±4.61）、（14.95±6.02）μg.mL-1和（1.56±0.48）、（1.51±0.47）μg.mL-1;tmax分别为（1.78±0.26）、（1.80±0.68）h和（1.20±0.33）、（1.06±0.29）h;AUC0→7分别为（28.86±5.56）、（29.15±5.82）μg.h.mL-1和（2.88±0.95）、（2.70±0.95）μg.h.mL-1;AUC0→∞分别为（31.12±6.03）、（31.65±5.79）μg.h.mL-1和（3.08±0.92）、（2.94±0.94）μg.h.mL-1。以实测值AUC0→t计算,受试制剂中阿莫西林与克拉维酸钾的相对生物利用度分别为（101.8±14.2）%和（98.0±27.4）%。结论本法专一性好,操作简便快捷,成功应用于阿莫西林-克拉维酸钾（8∶1）干混悬剂的生物等效性研究,阿莫西林-克拉维酸钾（8∶1）干混悬剂试验制剂相对参比制剂生物等效。     

阿莫西林克拉维酸钾(7∶1)片处方、工艺研究及溶出度考察

目的:研究阿莫西林克拉维酸钾片处方及工艺,并考察其溶出度.方法:通过吸湿性试验、处方及工艺优化确定制备工艺,制备了阿莫西林克拉维酸钾片,用高效液相色谱法测定其溶出度并与进口薄膜衣片进行比较.结果:本制剂必须采用干法制粒压片工艺,制备环境湿度控制在33%以下,自制片与进口片溶出相当.结论:阿莫西林克拉维酸钾片处方工艺合理.     

阿莫西林克拉维酸钾（7：1）片处方、工艺研究及溶出度考察

目的：研究阿莫西林克拉维酸钾片处方及工艺，并考察其溶出度。方法：通过吸湿性试验、处方及工艺优化确定制备工艺．制备了阿莫西林克拉维酸钾片，用高效液相色谱法测定其溶出度并与进口薄膜衣片进行比较。结果：本制剂必须采用干法制粒压片工艺，制备环境湿度控制在33％以下，自制片与进口片溶出相当。结论：阿莫西林克拉维酸钾片处方工艺合理。     

用HPLC-荧光检测同时测定阿莫西林和克拉维酸钾浓度

12名男性健康受试者采用随机交叉给药方法.单剂量口服试验药阿莫西林-克拉维酸钾干混悬剂(4:1)和对照药阿莫西林-克拉维酸钾(4:1)干混悬剂,阿莫西林500mg,克拉维酸钾125mg,进行人体生物利用度和药代动力学比较.用HPLC荧光检测同时测定阿莫西林和克拉维酸钾血浓度.结果试验药和对照药中阿莫西林的Tmax 1.58± 0.36和1.56± 0.34h;Cmax13.94± 2.20和13.38± 2.67 mg· L-1;T1/2 1.57± 0.19和1.53± 0.23h;AUC 52.28± 8.22和50.24± 9.44 mg· h· L-1,相对生物利用度104.89%± 7.73%.克拉维酸钾的Tmax 0.96± 0.37和1.06± 0.50h;Cmax 2.13± 0.44和2.69± 0.99mg·L-1;T1/2 1.27± 0.19和1.28± 0.32h;AUC 5.38± 0.83和5.66± 1.04mg·h· L-1,相对生物利用度95.91%± 11.21%.两种制剂的AUC和Cmax经方差分析和双单侧t检验,Tmax用非参数法统计,两种制剂中阿莫西林和克拉维酸钾两个组份均显示为生物等效.     

阿莫维酸钾胶囊的相对生物利用度

１０名健康志愿者随机交叉口服等剂量阿莫维酸钾胶囊或安奇颗粒剂,采用微生物法分别测定阿莫西林和克拉维酸钾的血药浓度。单剂量空腹口服３１２．５ｍｇ的受试药与参比药后,阿莫西林的Ｔｍａｘ。分别为０．９８±０．２ｍ和０．６７±０．２４ｈ　,Ｃｍａｘ　３．９９±１．６２ｇ／ｍｌ和４．７１±１．４９ｇ／ｍｌ,ＡＵＣ０１０．１５±２．６１ｇ／（ｍｌ·ｈ）和９．５５±２．０３ｇ／（ｍｌ·ｈ）;克拉维酸钾的Ｔｍａｘ分别为０．８９±０．３１ｈ和０．６６±０．１３ｈ,Ｃｍａｘ。则为０．７６±０．２４ｇ／ｍｌ和０．９２±０．３３ｇ／ｍｌ,ＡＵＣ０为１．９４±０．５４ｇ／（ｍｌ·ｈ）和１．９４±０．５９ｇ／（ｍｌ·ｈ）。阿莫维酸钾胶囊的阿莫西林相对生物利用度为１０６．９％,克拉维酸钾的相对生物利用度为１０６．７％。结果表明,阿莫维酸钾胶囊与安奇颗粒剂的药动学参数相似,两者具有生物等效性。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.