盐酸川芎嗪静脉注射的药物动力学研究

大鼠按30mg/kg静脉注射盐酸川芎嗪,体内药物动力学呈开放性二室模型。将每组所得数据的均数按Marquardt法迭代拟合,多项指标帮助选择最佳模型。模型分析得其参数为:t_(1/2α)=0.144lh,t_(1/2α)=1.6953h,K_(21)=2.2850h~(-1),K_(10)=0.8605h~(-1),K_(12)=2.0723h~(-1),AUC=83.3660mg·L·h,CL=0.3597L·kg·h~(-1),V_c=0.4182L·kg~(-1),V_(ss)=0.7975L·kg~(-1).分析结果表明:川芎嗪主要分布于血流丰富的大循环和组织,肾脏排泄少,肝脏为主要消除器官。     

依普黄酮固体分散体在大鼠的药物动力学评价(英文)

目的:评价依普黄酮固体分散体在大鼠体内的药物动力学行为。方法:测定它的药物动力学参数和相对生物利用度,采用高压液相色谱法测定大鼠血浆中依普黄酮的浓度。结果:大鼠灌胃依普黄酮固体分散体250mg·kg~(-1),其血药浓度-时间曲线符合一室模型,药物动力学参数为:K_e=0.21h~(-1),T_(1/2K_e)=5.19h,K_a=1.71h~(-1),T_(1/2K_a)=0.41h,T_(max)=0.67h,C_(max)=429μg·L~(-1),AUC=3916μg·h·L~(-1),相对生物利用度是323％。结论:依普黄酮固体分散体与依普黄酮的物理混合物比较,在大鼠体内有更多被吸收。     

稳定同位素结合GC-MS法测定大鼠体内川芎哚的药物动力学参数(英文)

目的:测定川芎哚(川芎Ⅲ号碱,perlolyrine)的药动学参数。方法:以[2-~(15)N]川芎哚为内标准及GC-MS的SIM(选择性离子监测)为检测手段,定量测定大鼠体内川芎哚的含量及其药代动力学参数。结果:大鼠灌胃给予川芎哚2mg·kg~(-1)后,川芎哚在大鼠体内呈二室模型分布,其药代动力学参数为:T_((1/2)α)=0.33h,T_((1/2)β)=4.52h,T_(1/2)(ka)=0.14h,T_(max)=0.35h,C_(max)=18.84μg/L,K_(12)=0.88h~(-1),K_(21)=0.42h~(-1),K_(10)=0.32h~(-1),V/F=109.22 L·kg~(-1),AUC=112.68μg·h·L~(-1)。结论:本法灵敏度高、特异性强且准确性好,为测定川草哚药代动力学参数提供了实用的分析方法。本研究为川芎哚临床应用提供了重要的参考资料。     

吗丙嗪的药物动力学研究

按75mg/kg给家兔灌胃吗丙嗪,体内药物动力学呈开放性二室模型。将每组数据按Marquardt法迭代拟合,多项指标帮助选择最佳模型。模型分析得其参数为:T_(1/2)α=0.19h,T_(1/2)β=4.96h,K_(21)=2.94h~(-1),K_(10)=0.69h~(-1),K_(12)=3.75h~(-1),AUC=98.91h·mg/L,CLs=0.76L·kg~(-1)·h~(-1),V/f(c)=1.09L·kg~(-1),Vss=1.51L·kg~(-1),分析结果表明:吗丙嗪主要分布于血流丰富的大循环和组织,肝脏为主要消除器官,肾脏及胃肠道均有排泄。     

维生素K_1微乳剂在大鼠体内的药物动力学

目的建立大鼠血浆中维生素K_1的高效液相色谱测定法,并应用于经灌胃给予维生素K_1微乳剂后的维生素K_1药动学研究。方法大鼠经灌胃给予维生素K,微乳剂3.77 mg·kg^(-1),于给药后不同时间采集血样,采用无水乙醇-乙醚(体积比为1:3)提取的方法处理血浆样品。采用反相高效液相色谱法测定维生素K_1的血药浓度,色谱柱为Thermo C_(18)柱(150 mm×4.6 mm,5μm),流动相为无水乙醇-水(体积比为90:10),流速为1.1 mL·min(-1),于给药后不同时间采集血样,采用无水乙醇-乙醚(体积比为1:3)提取的方法处理血浆样品。采用反相高效液相色谱法测定维生素K_1的血药浓度,色谱柱为Thermo C_(18)柱(150 mm×4.6 mm,5μm),流动相为无水乙醇-水(体积比为90:10),流速为1.1 mL·min^(-1),检测波长为270 nm,柱温为35℃。结果血液中的内源性物质不干扰测定。维生素K_1的线性为48～2 400μg·L(-1),检测波长为270 nm,柱温为35℃。结果血液中的内源性物质不干扰测定。维生素K_1的线性为48～2 400μg·L^(-1),r=0.995 3,定量下限为48μg·L(-1),r=0.995 3,定量下限为48μg·L^(-1),精密度、准确度、回收率均符合生物样品测定要求。主要药物动力学参数:t_(max)=1.0 h,t_(1/2)=7.61 h,ρ_(max)=0.77 mg·L(-1),精密度、准确度、回收率均符合生物样品测定要求。主要药物动力学参数:t_(max)=1.0 h,t_(1/2)=7.61 h,ρ_(max)=0.77 mg·L^(-1),AUC_(0-t)=2.87 mg·h·L(-1),AUC_(0-t)=2.87 mg·h·L^(-1),AUC_(0-∞)=3.21 mg.h·L(-1),AUC_(0-∞)=3.21 mg.h·L^(-1)。结论该方法适用于维生素K,微乳剂在大鼠体内的药物动力学研究。     

硫酸锌在兔体内的药物动力学研究

用原子吸收分光光度法测定兔血清锌、铜浓度。在1.53～15.3μmol/L 范围内为直线,r=0.9996,日内、日间变异系数小于4%,回收率99%,血清中最低检测限为0.122μmol/L。硫酸锌(Zn~(2 ),1mg/kg)静脉注射后,药时曲线符合二室开放模型:α=4.838h~(-1),β=0.320h~(-1),T_(1/2)α=0.149h,T_(1/2)β=2.25h,Vc=0.087L/kg,K_(12)=2.354h~(-1),K_(21)=2.051h~(-1),K_(10)=0.753h~(-1),AUC=34.316h·μg/ml。静注硫酸锌后,兔血清铜浓度降低,提示补锌时应注意对其他微量元素的影响。     

谷氨酸锌溶液剂在兔体内的药物动力学研究

谷氨酸锌溶液剂给兔口服后的药物动力学符合二室模型:k_a=1.25 h~(-1),α=0.64 h~(-1),β=0.37h~(-1),T_(max)=2.85 h,C_(max)=6.43μg/ml。谷氨酸锌溶液的相对生物利用度为66%。谷氨酸锌溶液、硫酸锌溶液和葡萄糖酸锌糖浆药物动力学的比较表明,谷氨酸锌为一种较好的补锌剂。     

体内药物累积法研究白血康的表观药物动力学

采用体内药物累积法测定小鼠 ip 白血康后的体内过程和药动学参数,白血康在小鼠体内的过程符合二室开放模型,模型方程为:体存率%=87.1711e~(-1.0952t) 138.1771e~(-0.0272t),t_(1/2)α=0.6328h,t_1/2β=25.48h,k_(21):0.6821h~(-1),k_(12)=0.3966h~(-1),k_(10)=0.0437h~(-1),Vc=3.55L/kg.     

头孢氨苄血药浓度的荧光法测定及药物动力学研究

本文研究了荧光法测定头孢氨苄的血药浓度及其药物动力学。实验结果表明,血清浓度在1～20μg/ml范围内,荧光强度与浓度有较好的线形关系,r=0.9975。回收率为94.7%±2.3%(n=5),CV=2.39%。浓度时间曲线(头孢氨苄0.5g,PO)显示为一室模型。平均药物动力学参数(n=8):Ka=1.7500(h~(-1)),K=0.7365(h~(-1)),T_(1/2)=0.9401(h),T_(max)=1.18(h),C_p=19.64(μg/ml),V_a/F=13568.2(ml)。     

血卟啉单甲醚（PsD—044）在家兔体内的药物动力学

用荧光分光光度法测定血卟啉单甲醚(PsD-044)的血药浓度激发光波长为395nm;发射光波长为613nm。PsD-044血浆浓度为10和20μg/ml时,测定回收率分别为98.31±1.17％(cv=1.19％)和97.76±6.35％(cv=6.80％)。PsD-044在家兔体内的药物动力学按三房室拟合。其主要药物动力学参数分别为:π=16.60h~(-1);α=0.546h~(-1);β=0.0303h~(-1);t_(1/2π)=0.0427h;t_(1/2α)=1.31h;t_(1/2β)=28.08h;V_c=0.0704L/kg;V_(area)=16.19L/kg;V_(ss)=6.26L/kg;Cl=0.487L/kg·h。     

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.