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试验旨在建立测定双峰驼血浆中对乙酰氨基酚浓度的反相高效液相色谱法(reversed phase high-performance liquid chromatography,RP-HPLC)。选用Supelco Discovery C18色谱柱(150 mm×4.6 mm,5 μm),以甲醇:水=20:80为流动相,流速为0.5 mL/min,紫外检测波长为248 nm,采用甲醇直接沉淀蛋白方法处理血浆样品。结果表明,对乙酰氨基酚的保留时间为6.5 min,分离度良好,无血浆杂峰干扰,且在0.08~10.24 μg/mL浓度范围内线性关系良好(R2=0.9997,n=8),检测限为0.10 μg/mL,日内和日间精密度RSD均小于7.0%,绝对回收率为80.39%~93.56%,相对回收率为94.66%~104.73%。因此,本试验所建立的RP-HPLC法操作简便、准确,重复性好,专属性强,适用于检测双峰驼血浆中对乙酰氨基酚浓度,为后续的借助特异性探针药物--对乙酰氨基酚研究双峰驼CYP1A酶的体内活性提供了可靠而准确的定量方法。 相似文献
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《Veterinary anaesthesia and analgesia》2021,48(5):637-644
ObjectiveTo determine if general anaesthesia influences the intravenous (IV) pharmacokinetics (PK) of acetaminophen in dogs.Study designProspective, crossover, randomized experimental study.AnimalsA group of nine healthy Beagle dogs.MethodsAcetaminophen PK were determined in conscious and anaesthetized dogs on two separate occasions. Blood samples were collected before, and at 5, 10, 15, 30, 45, 60 and 90 minutes and 2, 3, 4, 6, 8, 12 and 24 hours after 20 mg kg–1 IV acetaminophen administration. Haematocrit, total proteins, albumin, alanine aminotransferase, aspartate aminotransferase, urea and creatinine were determined at baseline and 24 hours after acetaminophen. The anaesthetized group underwent general anaesthesia (90 minutes) for dental cleaning. After the administration of dexmedetomidine (3 μg kg–1) intramuscularly, anaesthesia was induced with propofol (2–3 mg kg–1) IV, followed by acetaminophen administration. Anaesthesia was maintained with isoflurane in 50% oxygen (Fe′Iso 1.3–1.5%). Dogs were mechanically ventilated. Plasma concentrations were analysed with high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling. A Wilcoxon test was used to compare PK data between groups, and clinical laboratory values between groups, and before versus 24 hours after acetaminophen administration. Data are presented as median and range (p < 0.05).ResultsA two-compartmental model best described time–concentration profiles of acetaminophen. No significant differences were found for volume of distribution values 1.41 (0.94–3.65) and 1.72 (0.89–2.60) L kg–1, clearance values 1.52 (0.71–2.30) and 1.60 (0.91–1.78) L kg–1 hour–1 or terminal elimination half-life values 2.45 (1.45–8.71) and 3.57 (1.96–6.35) hours between conscious and anaesthetized dogs, respectively. Clinical laboratory variables were within normal range. No adverse effects were recorded.Conclusions and clinical relevanceIV acetaminophen PK in healthy Beagle dogs were unaffected by general anaesthesia under the study conditions. Further studies are necessary to evaluate the PK in different clinical contexts. 相似文献
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【目的】 研究葛根素(puerarin,PU)对对乙酰氨基酚(acetaminophen,APAP)所致小鼠急性肝损伤的保护作用,为临床上防治APAP引起的肝损伤提供新思路。【方法】 将40只4周龄体重(20±2) g的SPF级雄性昆明小鼠随机分为正常组(CON)、模型组(APAP)、葛根素低剂量组(L-PU)、葛根素高剂量组(H-PU)4组,每组10只。CON组正常饲养,L-PU和H-PU组分别以50和100 mg/kg葛根素灌胃,每天1次,连续给药7 d。最后一次给药后禁食16 h,APAP、L-PU和H-PU组均以200 mg/kg对乙酰氨基酚灌胃1次。继续禁食12 h,麻醉后经眼眶采血,颈椎脱臼处死小鼠,迅速采集肝脏,观察肝脏形态、计算肝脏指数;测定血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)活性,评价肝损伤情况;测定肝脏过氧化氢酶(catalase,CAT)活力及总抗氧化能力(total antioxidant capacity,T-AOC),评定肝脏氧化应激情况;测定谷胱甘肽转移酶(glutathione S-transferase,GST)及细胞色素P450家族2亚家族E成员1(cytochrome P450 2E1,CYP2E1)含量,分析APAP在肝脏的代谢情况;测定凋亡相关蛋白半胱氨酸蛋白酶-3(caspase-3)和caspase-9含量,评定肝脏细胞凋亡情况;制作肝脏病理组织切片,HE染色后观察肝脏组织学变化。【结果】 与CON组相比,APAP组肝脏质地坚硬,有明显出血,肝脏组织结构受到严重破坏,肝索排列紊乱,肝小叶结构不清晰,肝细胞大量坏死,肝脏指数及血清中ALT、AST水平显著上升(P<0.05),CAT活力、T-AOC及GST水平显著下降(P<0.05),caspase-3、caspase-9及CYP2E1含量显著上升(P<0.05)。与APAP组相比,L-PU和H-PU组小鼠肝脏形态结构及组织结构基本保持正常,且H-PU组效果更显著;L-PU和H-PU组小鼠肝脏指数和血清中AST、ALT水平显著降低(P<0.05),肝脏中CAT活力、T-AOC显著提高(P<0.05),caspase-9水平显著降低(P<0.05);此外,L-PU和H-PU组在提高小鼠GST水平的同时也显著降低了CYP2E1水平(P<0.05)。【结论】 葛根素对APAP所致的小鼠肝损伤具有明显的保护作用,可能与葛根素发挥抗氧化、抗凋亡、加速APAP解毒作用有关。 相似文献