UPLC分析大鼠血浆中阿齐沙坦浓度及其初步药代动力学研究

目的 采用UPLC建立大鼠血浆中阿齐沙坦浓度的测定方法,并探究阿齐沙坦在大鼠血浆中初步药代动力学情况。方法 选用缬沙坦为内标,色谱柱Kinetex C18（100 mm×2.10 mm,1.7 μm）,紫外检测波长254 nm,流动相为水-乙腈-冰醋酸（容积比为57∶42∶1）,流速0.2 mL/min,柱温25 ℃,进样量2 μL,建立在大鼠血浆中阿齐沙坦的分析方法。在此方法的基础上,经大鼠尾部静脉注射阿齐沙坦0.5 mg/kg,测定不同时间点其血浆浓度。实验数据运用DAS 2.1软件分析,得其主要药代动力学参数。结果 大鼠血浆中阿齐沙坦的线性范围为0.05～12.5 mg/L（r=0.999 9）,定量下限为0.05 mg/L,低、中、高浓度（0.1、1.0、10.0 mg/L）的提取回收率分别为（88.6±3.2）%、（86.5±2.2）%、（85.7±1.3）%（RSD<5%）,日内、日间精密度RSD不大于10%,准确度在85%~100%范围内。通过DAS 2.1软件拟合,阿齐沙坦的分布半衰期t1/2（α）为（0.39±0.04）h,消除半衰期t1/2（β）为（4.22±0.12）h,药时曲线下面积（AUC0-t）为每小时（53.25±2.46）mg/L。结论 本实验建立的UPLC操作快速、简单,且专属性强,适用于阿齐沙坦在大鼠血浆中浓度的分析及其药代动力学的探究。     

安眠酮薄层色谱扫描检测研究

本文通过实验研究改进了安眠酮的提取方法，以卡马西平为内标建立了血中安眠酮的薄层色谱扫描定性定量检测方法，研究了安眠酮在家兔体内的毒物动力学过程。     

Inter- and intra-subject variability in ethanol pharmacokinetic parameters: effects of testing interval and dose

Calculation of a blood alcohol concentration (BAC) at the time of an offence by forward or back-extrapolation, using population average values for ethanol pharmacokinetic parameters or a single estimate of individual specific parameters, ignores the possibility of inter- and intra-subject variability. In order to estimate inter- and intra-subject variability in the elimination rate and absorption rate, BAC was measured over time in 12 male volunteers on 4 occasions. Subjects received 0.44 g kg(-1) body weight of ethanol on the first study day, and 0.70 g kg(-1) body weight on subsequent study days 1, 11 and 12 weeks later, to enable comparisons in variability over short and long time periods and when the same or different doses were administered. Evidence of both inter- and intra-subject variability was found, with inter-subject variability substantially smaller than intra-subject variability when the dose varied. Forensically important differences in pharmacokinetic parameters were observed within individuals between occasions. These findings could have an important impact on medico-legal issues related to ethanol pharmacokinetics.     

水苏碱在大鼠体内的药动学

目的:研究水苏碱在大鼠体内的药动学。方法:采用柱前衍生化HPLC法,色谱条件为Kromasil C18色谱柱(4.6 mm×250 mm,5μm);流动相:甲醇-水(70∶30);流速:0.8 ml/min;检测波长:259 nm。从大鼠尾静脉注射盐酸水苏碱溶液,测定不同时间的血药浓度。用3P87药动学程序对血药浓度-时间数据进行拟合。结果:主要药动学参数为T1/2α(12.00min),T1/2β(101.07 min),Vc(0.298 L/kg),AUC(3833.456 min.μg/ml),CLs(0.0026 L.kg-1/min)。结论:水苏碱在大鼠体内呈二室开放模型。     

Pharmacokinetics of ethanol in patients with renal failure before and after hemodialysis

We studied the pharmacokinetics of ethanol in seven patients suffering from terminal renal failure before and after they underwent hemodialysis. Ethanol (0.40 g/kg) was administered in the morning after an overnight fast by a constant rate intravenous (IV) infusion over 45 min. After removing a mean fluid volume of 2.46±0.48 liters (±SD), span 1.76–3.43 liters by hemodialysis, the same subjects received a second IV infusion of ethanol after they had eaten lunch. At exactly timed intervals of 0, 45, 90, 105, 120, 135, 150, 165, and 180 min from the start of the infusion, two blood-samples were drawn and the plasma portion of one of them was obtained by centrifugation. The concentration of ethanol in blood and plasma was determined by headspace gas chromatography and the water-content of whole blood was determined from the change in weight after desiccation. Plasma always contained a higher concentration of ethanol than whole blood and the mean plasma/whole blood ratio in patients with renal failure was 1.07:1 (span 1.05–1.10). The rate of ethanol disappearance from blood (β-slope) was faster (0.185±0.013 versus 0.157±0.022 g/l/h), the C₀ value was higher (0.79±0.08 versus 0.73±0.10 g/l) and the apparent volume of distribution (V_d) of ethanol was lower (0.507±0.049 versus 0.558±0.078 l/kg) after hemodialysis. The water content of whole blood was significantly higher (P<0.001) before dialysis (88.6±1.97 g/100 ml) compared with after dialysis (87.4±2.01 g/100 ml). The higher V_d for ethanol and lower C₀ as well as higher blood-water content are to be expected for a over hydrated condition before hemodialysis. The swifter rate of ethanol elimination from blood (β-slope) after hemodialysis should be interpreted with caution because eating a meal before the second infusion of ethanol is a confounding factor. Nevertheless, the rate of elimination of ethanol from blood in patients with renal failure agreed reasonably well with values expected for healthy subjects, namely mean 0.15 g/l/h spanning from 0.10 to 0.20 g/l/h.     

酒精在人体内的代谢动力学研究

将16名健康男性志愿者随机分为两组，分别按含酒精0．65g／kg和0．80g／kg体重的剂量给予酒精饮料，于酒后不同时间点采取静脉血样。用乙醇脱氨酶（ADH）氧化分析法测血样酒精浓度（BAC），所得浓度-时间数据经用药代动力学软件分析拟合。结果表明，酒精在人体内的代谢符合非线性消除伴一级吸收的一室开放模型。据此，作者建立了描述酒精在人体内动态变化规律的数学模型。经验证，该模型符合度良好，可用于司法实践。     

排脓散汤剂和散剂中有效成分生物利用度的比较研究

目的 比较排脓散的汤剂与散剂中有效成分的药物代谢动力学参数,为排脓散的剂型选择提供依据.方法 以栀子苷为内标,采用UPLC-MS/MS法测定大鼠血液中芍药苷、橙皮苷、新橙皮苷和柚皮苷的含量,用乙酸乙酯法提取后,制备样品,然后使用Themo Scientific Syncronis C18色谱柱(2.1 mm×100 mm,2.7μm)在35℃下进行色谱分离,以水和乙腈为流动相,流速0.3 mL/min,进行负离子模式的多反应监测,用于测定血浆中标准品和内标.结果 4种有效成分含量在0.2～500 ng/mL范围内与峰面积呈良好的线性关系,提取回收率、稳定性、精密度均良好且达到测定要求.大鼠经单次给药后,与汤剂比较,排脓散散剂可显著增加橙皮苷的生物利用度(P<0.05),而不能显著增加新橙皮苷、柚皮苷和芍药苷的生物利用度(P>0.05).结论 排脓散散剂的生物利用度可能更优于汤剂.     

洛非西定对大鼠吗啡药代动力学的影响研究

用放射免疫测定方法 ,研究大鼠皮下注射盐酸吗啡及盐酸吗啡合并灌服盐酸洛非西定后 ,大鼠吗啡的药代动力学。结果表明 ,在合并用洛非西定后 ,大鼠血清吗啡的T1/2Ka由 0 2 5 7h增加到 0 349h ,T1/2K由 2 5 0 2h减少到 2 2 5 0h ,Cmax由 3330 μg·L-1减少到 16 48μg·L-1,AUC由 12 390h·μg·L-1减少到 72 80 6h·μg·L-1,CL由 0 80 7L·h-1·kg-1增加到 1 374L·h-1·kg-1。洛非西定可降低吗啡的吸收及血液中吗啡的浓度 ,加快吗啡在大鼠体内的总体清除率     

Review: Pharmacokinetics of illicit drugs in oral fluid

This article reviews studies that have measured drug concentrations in oral fluid following controlled dosing regimens. A total of 23 studies have been identified over the last 15 years. These show that the amphetamines including designer amphetamines, cocaine, cannabis and cocaine are quickly found in oral fluid following dosing and usually have similar time-courses to that in plasma. Following common doses peak oral fluid concentrations exceed 0.1 μg/mL and often even 1 μg/mL. The drug concentration will depend on whether a dilution step occurs with buffer as part of the sampling procedure. The uses of collectors that stimulate oral fluid usually reduce the drug concentration compared to a non-stimulated manner. This reduction will not disadvantage the recipient since it will potentially reduce the detectablity of drug in oral fluid compared to non-stimulated collections. Only one recent study has been reported for a benzodiazepine. This showed nanogram per milliliter concentrations for flunitrazepam. More studies are required for benzodiazepines and indeed for other drugs, particularly in multiple drug situations and where disease may affect the pharmacokinetics of drugs.