卡铂对肿瘤患者的药物动力学与药效学

目的:研究国产卡铂(CBP)的临床药物动力学与药效学,方法:12例肿瘤病人iv gtt CBP 400mg,用反相HPLC法测定血清CBP浓度,并按残数法拟合药物动力学模型和参数.结果:12例肿瘤病人iv gtt CBP结束时的平均血药浓度(?).为55.10±13.00)mg/L,消除半衰期(T._(2?))为(143.09±49.36)min,清除率(CL)为(45.17±16.68)ml min.有效组和无效组的(?)分别为(61.03±9.28)和(52.14±12.77)mg/L,T_(?)分别为(191.27±26.92)和(119.00±35.31)min(P<0.01),CL分别为(31.42±6.79)和(52.04±15.97)ml/min(P<0.05).在2～10h内.有效组血清CBP浓度高于无效组(P<0.05).结论:肿瘤病人iv gtt CBP的血药浓度存在明显个体差异,且疗效与血药浓度和清除快慢有关.     

大剂量奈替米星在新生儿体内的稳态药物动力学及临床疗效

目的:研究iv gtt奈替米星在新生儿体内的稳态药物动力学,观察疗效和安全性.方法:7例新生儿患者按7mg/kg.qd,iv gtt奈替米星,用药3d后用荧光偏振免疫法测定血药浓度,同时对奈替米星的抗感染效果及不良反应进行观察.结果:新生儿iv gtt奈替米星后,呈二房室动力学模型,主要药动学参数:C_(max)(18.38±5.43)μg/ml,T_(1/2β)(5.21±1.14)h.Vc(0.34±0.10)L/kg,CL(0.25±0.05)L/h,AUC(81.67±16.00)[(mg/L)·h]用药7d临床疗效满意并未发现不良反应.结论:肾功能正常的新生儿奈替米星qd iv gtt可获得较好的疗效并具有良好的安全性.     

左旋氧氟沙星血药浓度测定及药物动力学

目的:测定国产左旋氯氟沙星胶囊po后在人体内的药物动力学.方法:10例健康志愿受试者,单次po国产左旋氯氟沙星胶囊,用反相高效液相色谱法测定血浆中药物浓度.结果:左旋氧氟沙星药物动力学参数分别为:C_(?)=(2.12±0.21)μg/ml,t_(?)=(1.16±0 18)h,T_(1/2α)=(1.50±0.65)H,T_(1/2β)=(6.16±1.15)h,CL=(16.27±2.15)L/h,V_d=(70.33±10.94)L,AUC_(0→∞)=(13.72±1.03)(Mg/L)·h.结论:国产左旋氧氟沙星胶囊的主要药物动力学参数与国外文献报道基本一致.     

甲磺酸左氧氟沙星注射液的人体药物动力学

目的:测定国产甲磺酸左氧氟沙星注射液在人体的药物动力学.方法:12名健康受试者恒速iv gtt 200mg/0.5h,用HPLC法测定血清中和尿液中甲磺酸左氧氟沙星浓度.结果:经药物动力学计算程序拟合,符合二室模型.其初始血药浓度C_0为(3.54±0.24)mg/L,T_(1/2β)为(6.53±0.96)h,CL为(14.063±2.639)L/h,V/F为(38.529±3.913)L,AUC为(14.63±2.41)[(mg/L)·h].24h内累积尿药排泄率为(62.97±5.86)%.各项药物动力学参数与国外文献报道基本相符.结论:甲磺酸左氧氟沙星国产与进口产品的体内处置过程相同.     

抗心律失常药常咯啉的临床药代动力学

11名心律失常患者,静脉滴注CRL(55 μg/kg/min)60min的峰浓度为3.6±0.6μg/ml。其中8名PVBs患者滴注后26±9 min,PVBs完全消失,血浆中CRL有效浓度为2.6±0.7μg/ml。停滴后血药浓度迅速下降,降至2.0±0.6μg/ml时PVBs又复出现。3名结性早搏病人无效。药代动力学特性表征为单室模型,动力学参数:K=0.032±0.011 min~(-1);t_(1/2)=24±13 min;V_d=0.43±0.19 L/kg。健康志愿者6人,一次iv常咯啉50 mg,继以40μg/kg/min静滴55 min,血药浓度的范围在2.7～3.2μg/ml。对ECG和血压无明显变化。     

尼卡地平注射剂治疗重度高血压的临床疗效

目的:观察尼卡地平iv gtt治疗重度高血压的降压疗效及安全性.方法:多中心入选54例原发性重度高血压并接受尼卡地平治疗12h.观察临床症状、不良反应、BP和HR变化.结果:总有效率100%,用药后5min血压即明显下降,30min达显效水平,1.5h达最大降压效应并平稳维持至用药结束;达目标血压的药物滴速、累积量、时间分别为(55±28)μg/min、(2.10±1.52)mg、(38±19)min.维持目标血压的药物滴速为(49±25)μg/min,12h总量为(35.5±10.2)mg;不良反应发生率为 9.3%.结论:尼卡地平iv gtt能快速、有效地控制重度高血压的血压水平.     

国产四环格列齐特片在健康人体内的药物动力学及相对生物利用度

10名健康志愿者随机自身交叉单次po国产被试格列齐特片80mg和国产标准参比格列齐特片80mg后,应用高效液相色谱法测定血浆格列齐特浓度.格列齐特在健康人体内的血药浓度-时间过程符合二室模型.被试格列齐特片的药物动力学参数分别为:T_(1/2ka)=1.01±0.67h,T_(1/2β)=4.81±1.91h,T_(max)=3.32±0.92h,C_(max)=4.20±1.77μg/ml,AUC=45.89±22.98(μg·h)/ml.参比格列齐特的药物动力学参数分别为:T_(1/2Ka)=0.84±0.42h,T_(1/2β)=6.30±3.22h,T_(max)=3.28±0.79h,C_(max)=3.68±1.89μg/ml,AUC=41.42±19.35(μg·h)/ml.两种格列齐特片剂的各项药物动力学参数经3P87程序及统计学分析处理,被试格列齐特片对标准参比格列齐特片的相对生物利用度为107%.     

Ceftazidime的犬组织浓度及药代动力学研究

用6条健康犬进行了Ceftazidime的药代动力学研究及组织浓度测定。所有试验犬均静脉及肌肉交叉注射本品20mg/kg。药物血清浓度及组织浓度测定采用微生物杯碟法。 实验结果显示静脉及肌注后的血清药物浓度-时间曲线分别符合二室及一室开放模型。静注后即刻的平均血药浓度为167.28±15.73μg/ml,肌注0.75小时后的峰浓度为54.86±11.42μg/ml, 静注及肌注后的消除相半衰期分别为1.61小时和1.44小时,表观分布容积各为0.35L/kg和0.34L/kg。 静注及肌注Ceftazidime 20mg/kg 1小时后的组织浓度测定结果表明肾脏浓度最高,达189.03±79.38μg/ml(im)和257.04±59.19μg/ml(iv),其次是胆汁浓度。其他脏器组织浓度依下列次序减低:子宫、前列腺、肝、肺、小肠、胰腺、肌肉、心和脾。脑组织浓度最低,其值为0.31±0.lμg/ml(im)和0.77±0.09μg/ml(iv)。     

鱼腥草注射液引起过敏性休克1例

1 临床资料 患者,女,22a,因受凉后咳嗽、咽喉痛、发热3d来院就诊.查体示:T38.4℃,WBC 6.2×109/L,N 0.776.诊断:上呼吸道感染.即给予5%葡萄糖250ml加入鱼腥草40ml(长海医院制剂室,批号:010418)iv gtt,约5min左右,患者自感心慌,呼吸困难,烦燥不能坐.立即抬至床上,平卧吸氧.检查:脉搏细弱,无血压,意识模糊,四肢冰冷,口唇紫绀.诊断:鱼腥草引起的过敏性休克.立即iv地塞米松10mg,iv gtt 5%葡萄糖氯化钠加10%葡萄糖酸钙20ml,维生素C 2.0g.20min后意识逐渐恢复,皮肤渐变红,测BP 10.7/6.7kPa(80/50mmHg),P 73次/min,R 30次/min.观察2h,患者无不适而回家休息.     

国产头孢哌酮/舒巴坦复方制剂的人体药物动力学

目的研究国产头孢哌酮(CPZ)和舒巴坦(Sul)复方制剂在正常人体内的药物动力学.方法12名健康受试者恒速ivgtt2g国产或进口复方制剂(Sul、CPZ各1g),用RP-HPLC法分别测定CPZ和Sul的经时血药浓度.药-时数据用3P87程序拟合.结果药-时曲线符合二室开放模型.国产制剂单剂量ivgtt后,CPZ的AUC0→∞为(229.10±44.21)μg*h/ml,T1/2β为(2.20±0.49)h,MRT为(2.96±0.95)h,Cls为(4.7±0.9)L/h,Vc为(7.9±1.3)L;Sul的AUC0→∞为(65.90±6.71)μg*h/ml,T1/2β为(1.11±0.21)h,MRT为(1.53±0.40)h,Cls为(16.0±1.9)L/h,Vc为(15.7±4.6)L.方差分析显示主要药物动力学参数国产与进口制剂无统计学差异(P＞0.05).结论国产与进口复方制剂的药物动力学基本相似.     

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.