高效液相色谱荧光检测法测定人血浆中氟罗沙星浓度及其药代动力学研究

目的建立测定人血浆中氟罗沙星浓度的高效液相色谱方法，并用于其药代动力学研究。方法氟罗沙星血浆样品经甲醇沉淀蛋白后直接进样。色谱柱为Diamonsil C18柱，流动相为1％三乙胺（磷酸调pH至4．8）／乙腈（80／20，V／V），流速1．0mL·min^-1。采用荧光检测器，激发波长290nm，发射波长458nm。氟罗沙星药代动力学研究采用双周期交叉试验设计。结果氟罗沙星血浆浓度在0．025～8．00μg·L^-1范围内线性关系良好，低、中、高浓度质控样品的日内、日间精密度不超过5．16％，方法精密度99．1％～100．9％，提取回收率86．7％～92．0％。健康志愿者口服400mg氟罗沙星试验及参比制剂后主要药代动力学参数分别为：Cmax5．08±0．78和5．38±1．40μg·mL^-1，tmax 1．72±0．79和1．82±0．78h，t1/2 11．68±1．27和11．38±1．51h^-1，AUC0-∞ 78．44±11．44和76．53±13．24μg·mL^-1·h。结论该方法灵敏度高、定量准确，适用于氟罗沙星人体药代动力学研究。     

食物对氟罗沙星生物利用度的影响

目的　研究进食对氟罗沙星片剂生物利用度的影响。方法　在空腹和进食条件下分别给 12名健康志愿者口服氟罗沙星片剂 ,应用高效液相色谱法测定尿药浓度 ,以尿药排泄量计算生物利用度。结果① 60h尿药总排泄率 :空腹条件为 ( 67 13± 4 46) % ;进食条件为 ( 68 48± 4 3 8) % ;两组条件下无统计学意义 (P>0 0 5 ) ;②服药后 3h内尿药排泄速率 :空腹条件为 ( 10 47～ 14 5 2 )mg/h ,进食条件为 ( 4 40～ 10 65 )mg/h ,对前3h中的每小时以空腹与进食作配对t检验 ,P均小于 0 0 5。结论　进食对氟罗沙星片生物利用度无明显影响 ,但可延缓该药吸收速率。     

感染患者口服氟罗沙星片的药代动力学

目的:测定氟罗沙星在感染患者体内的药物代谢动力学。方法:HPLC法测定9例患者单剂量口服氟罗沙星200 mg后血清中药物浓度,并计算药代动力学参数。结果:氟罗沙星血清药物浓度-时间曲线符合一级吸收二室模型。药物吸收有一较大滞后时间期,平均为(0.25±0.14)h,吸收相t1/2Ka平均(0.88±0.17)h,消除t1/2β平均(13.22±2.78)h,达峰时间(3.99±0.40)h,药时曲线下面积(13.56±3.98)mg·h/L,消除速率(0.75±0.40)L/h,尿中原型药物24 h排出率为8.00％～13.00％,平均为(10.16±1.46)％,并且集中在8 h以后排出。结论:氟罗沙星片具有长效作用。     

氟罗沙星片在人体中的相对生物利用度

目的比较国产和进口氟罗沙星片的人体相对生物利用度.方法8名健康志愿者随机交叉,单剂量口服氟罗沙星200 mg,收集服药后72 h尿量,用荧光分光光度法测定尿药浓度. 结果国产与进口两种片剂尿药累积排泄量分别为(137.1±9.7) mg和(135.9±9.3) mg,国产片的相对生物利用度为100.88%.结论经统计分析,两种片剂在正常人体内的排泄过程相似,具有生物等效性.     

不同厂家氟罗沙星片的人体生物利用度比较

目的 :研究3个厂家生产的氟罗沙星片人体生物利用度的差异。方法 :12名男性健康志愿受试者交叉口服不同厂家氟罗沙星片400mg,用高效液相色谱法测定不同时间的尿药浓度 ,以尿药法计算其药动学参数。结果 :3种不同厂家氟罗沙星片服药后60h排药量无显著性差异 (P>0 05) ,而Tmax 则存在显著性差异 (P<0 05)。结论 :3个厂家氟罗沙星片的吸收程度无显著性差异 ,但吸收速率有差异。     

高效液相色谱荧光检测法测定健康志愿者血浆中氟罗沙星

目的建立测定人血浆中氟罗沙星浓度的高效液相色谱方法,并用于其药代动力学研究。方法采用加替沙星为内标,血浆样品经甲醇沉淀蛋白后直接进样。色谱柱为Diamonsil C18柱,流动相为1%三乙胺-磷酸缓冲液(pH4.8)/乙腈(80/20,V/V),流速1.0mL·min-1。采用荧光检测器,激发波长290nm,发射波长458nm。结果氟罗沙星血浆浓度0.025~8.00μg·L-1范围内线性关系良好(W=1/x,r=0.9999),低、中、高浓度质控样品的日内、日间精密度不超过5.16%,方法精密度99.1%~100.9%,提取回收率86.7%~92.0%。氟罗沙星血浆样品实验条件下均稳定。结论该方法灵敏度高、定量准确,适用于氟罗沙星人体药代动力学研究。     

高效毛细管电泳法测定人尿中氟罗沙星的含量

目的　建立高效毛细管电泳法测定人尿中氟罗沙星的含量。方法　采用高效毛细管电泳法 ,电泳缓冲液为磷酸盐 (5 0mmol·L-1) -SDS(10mmol·L-1) ,pH 4 .7,检测波长为 2 78nm。结果　在 5 0 .0～ 2 5 0 .0 μg·ml-1范围内线性良好 ,r =0 .9992。加样回收率在 94 .6 %～ 10 5 .9%之间 ,日内和日间RSD分别为 3.1%和 3.8% ,氟罗沙星的检测限为 2 .3μg·ml-1。结论　所用方法能快速、简便、经济地测定人尿中氟罗沙星的含量 ,可用于临床检验和药物制剂的质量控制     

氟罗沙星片的人体生物等效性

目的:研究氟罗沙星片的人体相对生物利用度,评价受试制剂与参比制剂的人体生物等效性。方法:20名男性健康志愿者采用随机交叉给药方案,单次口服400mg国产氟罗沙星片受试制剂和参比制剂,采用高效液相色谱法(HPLC)定量测定血浆氟罗沙星浓度,用DAS1.0程序计算两者生物利用度参数,并作出生物等效性评价。结果:单次口服400mg氟罗沙星受试制剂和参比制剂的主要生物利用度参数AUC0→t分别为(76 245.4±9 991.0)μg.h.L-1和(78 295.9±10 566.8)μg.h.L-1,AUC0→∞分别为(79 792.1±10 599.3)μg.h.L-1和(81 037.9±10 807.6)μg.h.L-1;Cmax分别为(5 218.8±1 493.8)μg.L-1和(4 983.9±910.7)μg.L-1;tmax分别为(1.8±1.0)h和(2.0±1.0)h。AUC0→t、AUC0→∞和Cmax经方差分析和双单侧t检验以及tmax经秩和检验表明两制剂的差异无显著性(P>0.05)。结论:两种制剂具有生物等效性,以AUC0→t计算受试制剂相对生物利用度为(98.4±13.4)%。     

联立方程组新解法在含氟罗沙星复方制剂分析中的应用

目的 :测定复方氟罗沙星栓及复方氟罗沙星滴耳液中2组分含量。方法 :采用联立方程组新解法不经分离直接测定复方氟罗沙星栓及复方氟罗沙星滴耳液中氟罗沙星、替硝唑及氟罗沙星、甲硝唑的含量。结果 :以286、317nm分别为复方氟罗沙星栓中2组分的测定波长 ,以蒸馏水为空白 ,氟罗沙星和替硝唑的平均回收率及RSD分别为100 17 %、0 44 %和99 96 %、0 37 % ;以286、318nm分别为复方氟罗沙星滴耳液中2组分的测定波长 ,以蒸馏水为空白 ,氟罗沙星和甲硝唑的平均回收率及RSD分别为100 65 %、0 65 %和99 92 %、0 21 %。结论 :本法操作简便快速 ,重现性好 ,可消除各处方中2组分的相互干扰 ,结果满意     

氟罗沙星葡萄糖注射液中氟罗沙星的含量测定

目的:建立氟罗沙星葡萄糖注射液中氟罗沙星含量的测定方法,为制剂的质量控制提供有效的分析手段.方法:采用高效液相色谱法,以Lichrospher-C18柱(200mm×4.6 mm,5μm)为色谱分析柱,乙腈-0.015 mol/L用磷酸调pH值至4.50的三乙胺水溶液(24:76)为流动相,流速为1.0 mL/min,紫外检测波长为286 nm,采用外标法计算氟罗沙星含量.结果:建立的色谱方法使杂质与主药分离良好,氟罗沙星浓度在4.180～41.80μg/mL内与峰面积线性关系良好,平均回收率为99.43%,RSD为0.42%.结论:反相高效液相色谱法专属性强,操作方便,结果准确,重现性好.     

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.     

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.