丙泊酚复合芬太尼麻醉对胃镜检查应激反应的影响

目的观察丙泊酚复合芬太尼麻醉对胃镜检查应激反应的影响。方法胃镜检查患者50例,分为观察组与对照组,观察组采用丙泊酚加芬太尼麻醉,对照组采用常规局部表面麻醉法。以两组患者检查前血浆皮质醇和血糖作为基础值,并于检查后即刻抽血测定血浆皮质醇及血糖值。用放免法测定血浆皮质醇含量。结果胃镜检查前两组患者血浆皮质醇均高出正常范围,观察组血浆皮质醇检查后较检查前显著降低(P<0.01),对照组血浆皮质醇检查后较检查前则显著增高(P<0.01);两组血糖检查后均增高,对照组增高较观察组明显(P<0.05),但均在血糖正常值范围内。结论丙泊酚复合芬太尼能在一定程度上抑制胃镜检查操作中的应激性反应,使胃镜检查更加安全。     

HPLC-MS-MS法测定人血浆中芬太尼浓度及其生物等效性研究

目的:建立液相色谱-串联质谱法(HPLC-MS-MS)测定人血浆中芬太尼的浓度。方法:以D5-芬太尼为内标,采用正己烷处理血浆样品。色谱柱为Thermo Hypurity C18(150mm×2.1mm,5μm),流动相为甲醇∶水(含0.1%甲酸)=(85∶15,V/V),流速为0.3mL/min,柱温40℃;质谱条件为电喷雾电离源(ESI),检测方式为正离子方式、多离子反应监测(MRM),用于定量分析的离子为芬太尼m/z 337.1→188.1,D5-芬太尼m/z 341.9→187.9。结果:芬太尼血药浓度在19.53～5000pg/mL范围内线性关系良好,定量下限为19.53pg/mL,日内和日间变异均小于5.16%,提取回收率均在90%以上;应用此方法研究了24名健康男性受试者使用两种芬太尼透皮贴剂的药代动力学特点,受试制剂对参比制剂的相对生物利用度为(94.0±19.5)%。结论:本法具有快速、简便、灵敏、准确等特点,适合人血浆中芬太尼浓度测定。两种制剂生物等效。     

HPLC-MS/MS法测定大鼠血浆中芬太尼浓度及其代谢机制研究

目的:建立以高效液相色谱-质谱(HPLC-MS/MS)法测定大鼠血浆中芬太尼浓度的方法,并研究肝脏对芬太尼代谢的影响。方法:以氨基比林为内标,采用正己烷提取处理血浆样品;色谱柱为InertsilODS-3,流动相为甲醇-0.5%甲酸溶液(90∶10);将大鼠分为正常对照组和无肝期组(夹闭肝门),静脉注射芬太尼20μg·kg-1,考察给药后1、2、3、5、10、15、20、30、45、60、75、90min芬太尼血药浓度的变化及其药动学情况。结果:芬太尼、氨基比林与血浆中内源性杂质分离良好;芬太尼检测浓度的线性范围为0.5～400ng·mL-1(r=0.9997),平均回收率为96.90%～102.32%,日内和日间RSD均小于10.56%。与正常对照组比较,无肝期组芬太尼浓度下降明显减慢,AUC0～(P<0.05)、t1、Cmax均增加。结论:肝脏是芬太尼的主要代谢器官,但也存在肝外代谢。t/2z所建立的方法可用于大鼠体内芬太尼的含量测定。     

舒芬太尼复合丙泊酚麻醉对妇科腹腔镜手术患者血流动力学的影响

目的探讨舒芬太尼复合丙泊酚麻醉对妇科腹腔镜手术患者血流动力学的影响。方法选择68例ASAⅠ-Ⅱ级择期行妇科腹腔镜手术患者,随机分为舒芬太尼-丙泊酚组和芬太尼-丙泊酚组,两组患者分别使用舒芬太尼或芬太尼复合丙泊酚静脉麻醉。两组患者术中和术后无创监测平均动脉压（MAP）、心率（HR）。并于麻醉前（T1）、气腹前（T2）、气腹后20min（L）和解除气腹后20min（L）四个不同时点测定血浆NO和ET．1水平。结果气腹后20min芬太尼-丙泊酚组MAP均较麻醉前明显升高,而舒芬太尼-丙泊酚组较麻醉前无明显变化,较芬太尼．丙泊酚组明显降低。芬太尼-丙泊酚组气腹后20min血浆ET-1水平升高幅度明显高于舒芬太尼-丙泊酚组,而血浆NO水平升高幅度却明显低于舒芬太尼-丙泊酚组。结论舒芬太尼复合丙泊酚静脉麻醉对患者术中血流动力学的稳定性明显强于芬太尼复合丙泊酚静脉麻醉。     

瑞芬太尼在气管插管全麻中的应用

目的：通过对患者气管插管的心血管反应、血浆血管紧张素、肾素活性和醛固酮的变化分析,了解瑞芬太尼和芬太尼对心血管的影响,以期对临床气管插管用药提供经验。方法：将1000例实行全麻手术患者随机分为治疗组和对照组,每组各500例。其中治疗组使用瑞芬太尼进行麻醉诱导,对照组使用芬太尼进行麻醉诱导。然后对诱导前及后3min的收缩压、舒张压、平均动脉压和心率进行观察并记录。同时抽取静脉血对血浆血管紧张素、肾素活性及醛固酮水平进行测定,最后比较其差异。结果：两组插管前后的收缩压、舒张压、平均动脉压、心率、血浆血管紧张素、肾素活性和醛固酮的水平相比,差异有统计学意义,P〈0.05。结论：瑞芬太尼与芬太尼相比,其对抑制插管应激反应优于芬太尼,更利于患者血流动力学及肾素-血管紧张素系统的稳定。     

芬太尼、舒芬太尼麻醉对心脏直视手术患儿应激和心肌肌钙蛋白Ⅰ影响的比较

目的:比较舒芬太尼、芬太尼麻醉对心脏直视手术患儿应激和心肌肌钙蛋白I的影响。方法:择期行先天性心脏畸形矫治术的患儿30例,年龄8~36月,体重5.8～14 kg,随机分为芬太尼组和舒芬太尼组,每组15例(n=15),分别采用等效剂量的芬太尼和舒芬太尼静脉复合麻醉。在体外循环前、停机5 min、停机4 h、停机8 h和停机16 h测定血浆皮质醇、乳酸和心肌肌钙蛋白Ⅰ的水平。结果:体外循环前,血浆皮质醇、乳酸和肌钙蛋白Ⅰ水平差异无统计学意义,体外循环后,三项指标有不同程度升高,但舒芬太尼组明显低于芬太尼组。结论:舒芬太尼麻醉用于小儿心脏直视手术,能够更好地抑制应激反应,减轻心肌损伤。     

国产芬太尼在法洛四联症患儿的药代动力学研究

目的;探讨法洛四联症根治术患儿大剂量应用国产芬太尼的药代动力学。方法：随机选择法洛四联症根治术患儿８例,芬太尼１０μｇ／ｋｇ静注后用微量泵持续输注１μｇ／（ｋｇ．ｍｉｎ）至切皮,用ＧＣ－ＭＳ测定血浆芬太尼浓度,并计算药药动力参数。结果：芬太尼的药代动力学符合开放型三室模型,其快速分布半衰期（ｔ１／２π）,缓慢分地衰期（ｔ１／２α）和消除半衰期（ｔ１／２β）分别为１．３０,１１．０和３７３．５ｍｉｎ     

LC-MS/MS法测定比格犬血浆中芬太尼浓度及药动学研究

目的 建立比格犬血浆中芬太尼的液相色谱-串联质谱（LC-MS/MS）测定方法,并用于药动学研究。方法 采用固相萃取（SPE）法从血浆中提取芬太尼和内标芬太尼-d5,建立比格犬血浆中芬太尼的LC-MS/MS测定方法,进行特异性、准确度、精密度、基质效应、灵敏度、稀释可靠性、稳定性方法学验证;8只比格犬,分别单次iv给予芬太尼的生理盐水溶液400 mg/只,用LC-MS/MS测定给药后血浆中芬太尼浓度,并用WinNonLin软件计算药动学参数。结果 芬太尼的线性范围为2～1 000 pg/mL,精密度、准确度、基质效应、灵敏度、稀释可靠性、稳定性均符合生物样品分析要求。比格犬体内芬太尼药动学参数：t_1/2为（4.53±0.748）h,AUC_0-t为（19 659±3 889）h·ng/mL,CL为（2 259±284）mL/（h·kg）,符合二室开放模型。结论 建立的LC-MS/MS分析方法准确灵敏,适用于芬太尼的药动学研究。     

美托洛尔和芬太尼对高血压病人气管插管致循环系统反应的作用

目的:考察美托洛尔和芬太尼对高血压病人气管插管致循环系统反应的作用。方法:选取4 0例需气管插管全麻手术的高血压病人,随机分成4组,每组1 0例。于麻醉诱导前各组分别静脉输液:A组用生理盐水(1 0mL) ;B组用美托洛尔4 0 μg kg 生理盐水(1 0mL) ;C组用芬太尼2 μg kg 生理盐水(1 0mL) ;D组用美托洛尔4 0 μg kg 芬太尼2 μg kg 生理盐水(1 0mL)。测定插管前后心率(HR)、收缩压(SAP)、舒张压(DAP) ,并计算心率收缩压乘积(RPP) ,于相应时间点采集动脉血标本测定血浆去钾肾上腺素(NA)和肾上腺素(Ad)的浓度。结果:气管插管后1和3分钟,A组病人的SAP、DAP、HR、RPP及血浆NA和Ad浓度均有显著升高(P <0 . 0 5 ) ,B组病人插管后血浆NA浓度明显大于C、D组(P <0 .0 5 ) ,D组病人SAP、DAP、HR及血浆NA和Ad浓度较基础值无明显差异(P >0 . 0 5 )。结论:行全麻手术的高血压病人气管插管时存在明显的循环系统应激反应,单独应用美托洛尔4 0 μg kg或单独应用芬太尼2 μg kg仅能部分抑制插管反应,二者联用则能更有效地抑制插管反应。     

高效液相色谱法测定人血浆中芬太尼浓度

目的:建立高效液相色谱测定人血浆中芬太尼浓度的方法.方法:采用外标法,以Kromasil-C18(4.6 mm×250 mm,5μm)为固定相,舍0.02 mol·L-1磷酸二氢钠水溶液-乙腈(65:35)为流动相,流速1 mL·min-1,检测波长为220 nm.结果:血浆芬太尼浓度在6～300μg·L-1范围内与峰面积呈良好线性关系(r=0.999 6),最低检测浓度为5 μg·L-1,方法回收率为(92.6±1.5)%,提取回收率为(84.9±1.4)%,日内RSD为1.8%,日间RSD为2.6%.结论:本方法具有较高的准确度,线性范围宽,方法灵敏,专一性好,操作简便,适用于临床芬太尼血药浓度的测定及临床药动学研究的要求.     

Biphasic effect of a kappa-opioid receptor agonist on plasma oxytocin levels in rats

The effect of the kappa-opioid receptor agonist, bremazocine, on plasma oxytocin levels in rats was measured by a sensitive radioimmunoassay. Initially, a decrease in plasma oxytocin levels was seen 30 min after injection. This was in accordance with the bremazocine inhibition of oxytocin release after submaximal electrical stimulation seen in isolated neurointermediate lobes. The initial decrease in plasma oxytocin reversed, and 4 h after injection of bremazocine a 20-fold increase in the oxytocin level was seen. The rise in plasma oxytocin was paralleled by a rise in plasma sodium. The biphasic time course of the plasma oxytocin response can be explained by a combination of an inhibition of oxytocin release from the neurohypophysis and an increased water excretion leading to an elevation in plasma sodium, which may be responsible for the late rise in plasma oxytocin. Down-regulation of the opioid receptors may also contribute to the delayed rise in plasma oxytocin.     

Pharmacokinetics of orally administered hexobarbital in plasma and saliva of healthy subjects

Hexobarbital (HB) concentrations were determined in plasma and saliva of 8 healthy subjects, following oral administration of 500 mg HB-Na. Mean plasma half-lives were 3.2 +/- 0.1 h, and salivary half-lives 3.3 +/- 0.2 h. Mean plasma clearance was 22.9 +/- 2.3 1 h-1. There was a linear relationship between HB concentrations in saliva and plasma (r = 0.92). Mean salivary levels were 34 per cent of plasma levels. Salivary pH was constant throughout the experiment, 7.06 +/- 0.09. There was an inconsistent tendency of the saliva over plasma ratios to increase as a function of time. The percentage of protein binding calculated from saliva over plasma ratios was in reasonable agreement with in vitro data of equilibrium dialysis, 64.1 +/- 2.6 per cent and 65.9 +/- 0.8 per cent, respectively. The experiment was repeated in 4 subjects, and considerable intraindividual differences were shown to exist in saliva over plasma ratio, half-lives, and protein binding. It was concluded that HB elimination half-lives can relatively accurately be determined from salivary concentrations. Oral plasma clearance can only be estimated if the individual saliva over plasma ratios are known; this would require the taking of at least one blood sample during the experiment. When employing HB as a model substrate for drug metabolizing enzyme activity in vivo, the determination of its pharmacokinetic parameters, particularly oral plasma clearance as a reflection of cytochrome P-450 activity, cannot be achieved by taking saliva samples only.     

Components of the renin-angiotensin system in the plasma of Bothrops jararaca.

By means of high voltage electrophoresis experiments it could be demonstrated that the dipeptide hydrolase present in the plasma of Bothrops jararaca is similar to the angiotensin I converting enzyme of human plasma. Therefore, angiotensin I can be considered as a probable natural substrate for this potent snake peptidase in contrast to bradykinin, which is excluded in that case, since this snake plasma was previously found to be deficient in intrinsic kinin releasing system. On the other hand, the presence of angiotensinase activity in this snake plasma could also be demonstrated. Through the pharmacological comparison of angiotensin II with the pressor peptide released from the Bothrops jararaca plasma by chymotrypsin, an indirect indication of the presence of angiotensinogen in the plasma of this reptile was obtained.     

Plasma catecholamine metabolites as markers for psychosis and antipsychotic response in schizophrenia.

The objective of this study was to determine the association between the patterns of change in the dopaminergic metabolite plasma homovanillic acid (HVA), the noradrenergic metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), and psychosis following haloperidol withdrawal in schizophrenic patients. Weekly plasma measurements were obtained in 107 subjects with schizophrenia or schizoaffective disorder. Random regression was used to control for individual variance while modeling metabolite changes over time and relationships with psychosis. Changes in plasma MHPG were not significantly associated with relapse or psychosis, while increased plasma HVA was found to be associated with relapse. Psychosis was correlated negatively with plasma HVA levels. The current analysis, controlling for individual variance, indicates that there is evidence for pharmacological effects on plasma HVA, but not plasma MHPG. In addition, these metabolites do not appear to be direct markers of psychosis, but may be associated with a compensatory response by the system to return to the steady state.     

Inorganic and Methylmercury Levels in Plasma are Differentially Associated with Age,Gender, and Oxidative Stress Markers in a Population Exposed to Mercury Through Fish Consumption

This study aimed to determine the concentrations of plasma methylmercury (Me-Hg) and inorganic mercury (I-Hg) in a population exposed to Me-Hg. In addition, associations between each form of mercury (Hg) and gender, age, plasma selenium (Se), and oxidative stress markers were also investigated. The mean plasma I-Hg level was 5.7 μg/L while the mean for plasma Me-Hg was 3.6 μg/L, representing approximately 59 and 41% of the total Hg in blood, respectively. However, several plasma samples contained higher percentages of Me-Hg. Age displayed a direct linkage with plasma I-Hg levels, whereas gender did not correlate with any of the Hg species. In addition, fish intake was only correlated with and a predictor of plasma Me-Hg, suggesting that plasma I-Hg levels originated endogenously through a demethylation reaction that needs to be verified. Further, plasma Me-Hg was markedly correlated with adverse effects to a greater extent than plasma I-Hg and may be considered a valuable, reliable internal dose biomarker for Hg in chronically Me-Hg- exposed individuals.     

ACTIVATION BY PUFF ADDER VENOM OF INACTIVE RENIN IN NORMAL AND HYPERTENSIVE RAT PLASMA

Inactive renin has been studied extensively in human plasma, but in animal plasma its accurate quantification has proved more difficult, due partly to higher activity of plasma protease inhibitors. Such activity in human plasma can be conveniently destroyed by a metalloprotease in Bitis arietans venom, with concommitant release of endogenous enzyme activities, such as plasma kallikrein, that then activate inactive renin. It was therefore of interest to look for inactive renin in rat and rabbit plasma using this approach, so providing, in addition, a comparison for the disparate data of other groups who have used trypsin or acid for activation. In both rat and rabbit plasma the proportion of inactive renin was 62% of total renin, whereas human plasma contained more inactive renin and a higher proportion, 82%. A higher concentration of venom was required for rat (33 ug venom/ml plasma) and rabbit (4 micrograms/ml) than needed for activation, at a similar rate, in human plasma (1 microgram/ml). When applied to studies of rats made hypertensive and hyper-reninaemic by aortic ligation for 5 days, higher total (active + inactive) renin was observed. The proportion of inactive renin, as a percentage of total renin in plasma collected at this time, was, however, found to diminish significantly. In conclusion, puff adder venom activates inactive renin in rat and rabbit plasma and can be used to study physiological changes in inactive renin in such animal plasma.     

Kinetics of diphenylhydantoin in uraemic patients: Consequences of decreased plasma protein binding

Summary Diphenylhydantoin (2 mg/kg) was infused intravenously in four uraemic patients and four healthy volunteers and its plasma concentration measured during and after the infusion. The plasma concentrations were considerably lower in the uraemic subjects and the apparent volume of distribution was higher. These observations could be explained by the lower plasma protein binding of diphenylhydantoin in the uraemics. The overall elimination rate constant was greater (shorter half-life) in the uraemic patients. This difference could not be explained by reduced plasma protein binding, but it might be due to induction of diphenylhydantoin metabolism in the uraemic state. it is concluded that monitoring of the plasma levels of drugs in uraemic patients should be combined with determination of the extent to which the compounds are bound to plasma proteins.     

Activation of dog plasma kininogenase with glass

The activity of glass-activated kallikreins in dog plasma was determined by measuring both kininogenase and p-toluensulphonyl-l-arginine methyl ester (TAME) esterase activities. Non-contact plasma, after being shaken with glass beads, was centrifuged immediately at 4° to sediment the glass beads and the supernatant was used for the experiments. Glass activation of dog plasma was more effective on TAME esterase activity. When the supernatant alone was preincubated at 37°, its kininogenase activity was suppressed about 50 per cent, while TAME esterase activity was unchanged. High kininogenase activity in the supernatant could be induced by treatment with 50% ammonium sulphate, suggesting the presence of peculiar inhibitors for kininogenase activity in glass-activated dog plasma. Kininogenase inhibitors in plasma were separated by gel filtration on Sephadex G-200; there were two inhibitors which were able to suppress kininogenase activity in glass-activated dog plasma. When dog plasma was preincubated with lima bean trypsin inhibitor, generation of both kininogenase and TAME esterase was significantly suppressed during contact with glass beads. Acetone-activated dog plasma could be reactivated by glass contact, although the level of kininogenase activity was lower than that by glass activation alone. The non-absorbed supernatant of glass-activated dog plasma formed kinins from rat kininogen. The present results suggest that the kinin-forming system by glass activation in dog plasma is not qualitatively different from that in human plasma with the exception of the presence of potent kininogenase inhibitors in the plasma.     

氨茶碱血药浓度监测及个体化给药方案设计

目的测定氨茶碱血药浓度，并设计个体化给药方案。方法先用双波长紫外分光光度法测定血药浓度，再根据血药浓度调整用药剂量。结果当血药浓度在有效浓度范围内时，可用稳态时一点法设计给药方案。结论此方法可为临床调整剂量提供依据。     

微透析法测定虎杖苷的体外血浆蛋白结合率及与超滤法的比较

目的 采用微透析技术研究虎杖苷的体外血浆蛋白结合率,并与超滤法比较。方法 微透析探针依次浸入含虎杖苷20,60,200μg·mL1的大鼠、人血浆中,灌注器以2.5μg·min1的流速依次灌注含虎杖苷0,10,30,100,300μg·mL1的生理盐水,每15min收集1次样品,HPLC分析虎杖苷浓度。以灌注液与透析液中虎杖苷的浓度差对灌注液浓度进行线性回归,计算血浆中游离虎杖苷的浓度,进而计算虎杖苷的血浆蛋白结合率,并与超滤法进行比较。结果 微透析测定虎杖苷与大鼠、人血浆蛋白结合率平均值分别为86.15%,89.08%,超滤法分别为85.60%和87.24%,两种方法结果比较接近。结论 虎杖苷与大鼠、人血浆蛋白有较高的结合率,微透析法和超滤法结果一致。