布比卡因微球剂型对大鼠坐骨神经阻滞的效果

目的 评价布比卡因微球剂型对大鼠坐骨神经阻滞的效果.方法 雌性Wistar大鼠60只,体重230～250 g随机分为4组:对照组(A组,n=6)、布比卡因组(B组,n=6)、空白微球组(C组,n=24)和微球给药组(D组,n=24).A组和B组给药方法:在右侧大转子和坐骨结节之间连线的靠近大转子的1/3处,用27号针向前内侧方向针尾抬高45°进针,直至针尖抵达坐骨后给药,A组和B组分别注射生理盐水1 ml或0.5%布比卡因20 mg/kg 1 ml;C组和D组给药方法:采用外科植入术法给药,C组和D组分别于坐骨神经周围的肌肉间隙中植入空白微球或布比卡因微球400 mg/kg(布比卡因载药量26.75%),于给药前和给药后评价运动阻滞程度,并测定热痛阈.给药后28 d内观察不良反应的发生情况,C组和D组分别在给药后2 d、7 d、14 d和28 d随机取6只大鼠,取用药部位肌肉和坐骨神经组织,光镜下观察病理学结果.结果 与A组比较,B组在给药后0.5～3 h时运动阻滞程度及热痛阈增加,D组在给药后0.5～36 h时运动阻滞程度增加,在给药后0.5～72 h时热痛阈增加(P＜0.05).C组和D组给药后用药部位肌肉组织未见变性和坏死,仅有轻微的炎性反应,用药部位坐骨神经未见轴索变性和脱髓鞘.结论 大鼠布比卡因微球剂型坐骨神经阻滞可延长阻滞时间,组织相容性较好.     

罗哌卡因含或不含肾上腺素硬膜外麻醉的药效学和药代动力学

目的观察肾上腺素对１％罗哌卡因硬膜外阻滞的药效学和药动学影响。方法选择ＡＳＡⅠ～Ⅱ级行下腹部手术病人１６例,随机分为两组,每组８例。分别用１％罗哌卡因２ｍｇ· ｋｇ~－１（Ｒ组）和加入１： ２００ ０００肾上腺素的 １％罗哌卡因 ２ｍｇ· ｋｇ~－１（ＲＥ组）行硬膜外阻滞,对比两组药效学和药代动力学指标。结果两组药效学指标、Ｃｍａｘ和ＡＵＣ间均无显著性差异。与Ｒ组相比,ＲＥ组的Ｔｍａｘ明显后延（Ｐ＜０．０１）,Ｋ值明显降低（Ｐ＜０．０５）。结论 １：２００ ０００肾上腺素对１％罗派卡因硬膜外阻滞的药效学没有影响,但可以减缓罗哌卡因的吸收和清除。     

年龄因素对患者硬膜外注射左旋布比卡因药效学和药代动力学的影响

目的 探讨年龄因素对患者硬膜外注射左旋布比卡因药效学和药代动力学的影响.方法 择期拟行下肢手术患者45例,年龄30～72岁,体重52～83 ks,ASA Ⅰ或Ⅱ级,按不同年龄分为3组:Ⅰ组(≤45岁)、Ⅱ组(46～64岁)和Ⅲ组(>64岁),每组15例,均采用腰段硬膜外麻醉,左旋布比卡因(7.5 mg/ml)用量1.8 mg/kg(含肾上腺素5 μg/ml).经L1,2硬膜外穿刺成功后,注射试验量0.5%左旋布比卡因3 ml,3 min后注射剩余量0.75%左旋布比卡因.硬膜外注药后记录感觉和运动阻滞效果及不良反应的发生情况;每组随机选择9例,于注药后即刻、注药后10、20、30、45、60、90、120、180、240、360、480、840、和1 440 min时采用高效液相色谱法测定血浆左旋布比卡因浓度,绘制血浆左旋布比卡因浓度-时间曲线,计算3组药代动力学参数.结果 与Ⅰ组比较,Ⅲ组最高感觉阻滞平面高,感觉和运动阻滞维持时间长,(P<0.05);各组麻醉效果优良率均达100%;各组左旋布比卡因的血浆药物浓度-时间曲线均符合二房室开放模型;硬膜外注药后1 440 min时Ⅱ组和Ⅲ组左旋布比卡因血药浓度高于Ⅰ组(P<0.05);Ⅱ组和Ⅲ组左旋布比卡因消除半衰期明显长于Ⅰ组,Ⅲ组明显长于Ⅱ组(P<0.05).结论 不同年龄患者硬膜外注射0.75%左旋布比卡因1.8 mg/kg安全有效;随年龄增加,感觉阻滞平面升高、感觉和运动阻滞恢复时间延长,药物代谢明显减慢.     

肾移植术硬膜外罗哌卡因药效学和药代动力学研究

目的 观察肾移植术患者罗哌卡因硬膜外麻醉时药代动力学和药效学的变化。方法选择肾移植术病人8例（R组）;年龄体重相匹配的肾功能正常,行下腹部或下肢手术病人8例（C组）。应用0.75％罗哌卡因行硬膜外阻滞,测定感觉阻滞、运动阻滞程度;以高效液相法测定罗哌卡因血浆浓度,测定血浆α1-酸性糖蛋白浓度。结果　R组感觉阻滞上界固定时间为（20.00±4.63）min,比对照组[（32.14±8.09）min]明显快（P<0.05）;麻醉持续时间明显延长,分别为（60.00±27.69）min,（43.10±27.64）min,P<0.05。R组血浆α1-酸性糖蛋白浓度[（125.49±46.84）mg/dl]明显高于C组[（69.69±20.39）mg/dl）]（P<0.05）。R组罗哌卡因血药浓度-时间曲线 AUC（496.46±237.84）明显高于C组（304.09±100.77）（P<0.05）。而运动阻滞时间、Tmax、Tβ1/2、Cmax两组无显著性差异。结论 硬膜外0.75％罗哌卡因可为肾移植术提供良好的麻醉。肾衰对罗哌卡因药效学和药代动力学有不同程度的影响。     

硬膜外阻滞时罗哌卡因和布比卡因的药代动力学

目的 研究国人在硬腊外阻滞时罗哌卡因和布比卡因的药代动力学特征。方法 选择１４例手术病人、随机分为两组、硬膜外阻滞时,分别注产哌卡因２．０ｍｇ／ｋｇ或布比卡因２．０ｍｇ／ｋｇ。用气相色谱法测定血浆药物浓度。结果 罗哌卡因和布比卡因的药＝时曲线均会合二室开放模型。ｔ１／２ｋａ分别为０．２２小时和０．１４小时,Ｔ分别为０．５１和０．４７小时,Ｃａｍｘ分别１．０６ｍｇ．／ｋｇ．Ｌ＾１和１．４４ｍｇ．Ｌ＾     

患者硬膜外注射不同浓度左旋布比卡因的药代动力学

目的 探讨患者硬膜外注射不同浓度左旋布比卡因的药代动力学.方法 择期行结肠癌根治术、经腹或腹会阴直肠癌根治术患者20例,ASA Ⅰ或Ⅱ级,年龄35～59岁,随机分为0.75%左旋布比卡因组(Ⅰ组)和0.5%左旋布比卡因组(Ⅱ组),每组10例.麻醉方法为腰段硬膜外阻滞联合全麻.经L1,2硬膜外穿刺成功后,分别经2 min注入0.75%或0.5%左旋布比卡因2 mg/kg.硬膜外注药结束后30 min内记录感觉和运动阻滞效果,记录不良反应发生情况.于注药后即刻、注药后10、20、30、45、60、90、120、210、300、420、540、660和840 min时取中心静脉血3 ml,采用高效液相色谱法测定血浆左旋布比卡因浓度,绘制血浆左旋布比卡因浓度-时间曲线,计算2组药代动力学参数.结果 2组血浆左旋布比卡因浓度-时间曲线均符合二房室开放模型;2组药代动力学参数比较差异均无统计学意义(P＞0.05).结论 0.75%和0.5%左旋布比卡因2mg/kg腰段硬膜外阻滞安全性高,血浆药物浓度-时间曲线均符合二房室开放模型,两者药代动力学特性无差异.     

罗哌卡因在硬膜外阻滞时的药代动力学研究

罗哌卡因 (Ｒｏｐｉｖａｃａｉｎｅ)是一种新型长效的酰胺类局麻药 ,其化学结构为纯Ｓ型对映异构体。它对中枢神经系统和心血管系统毒性低 ,低浓度时具有感觉—运动神经阻滞分离现象。本研究拟通过对罗哌卡因在硬膜外阻滞时药代动力学的研究 ,探讨不同浓度的罗哌卡因进入硬膜外腔后在人体的吸收、分布和消除规律 ,以期对临床工作中合理用药提供较好的药理性理论依据。表 1　药代动力学参数项目Ⅰ组 (9例 )Ⅱ组 (9例 )Ｔ1 2Ｋａ(ｍｉｎ) 9 86± 1 6110 3 4± 2 5 5Ｔ1 2ａ(ｍｉｎ) 16 66± 5 72 15 71± 5 11Ｔ1 2 β(ｍｉｎ) 87 13…     

肾上腺素对丁哌卡因肌间沟臂丛神经阻滞的药效学与药代动力学的影响

目的:了解肾上腺素对丁哌卡因肌间沟臂丛神经阻滞的药效学及药动学影响。方法:选择ASA Ⅰ～Ⅱ级肩部或上肢择期手术患者16例,随机分成两组,试验组与对照组各8例,分别用含或不含肾上腺素的0.75％丁哌卡因2mg/kg行肌间沟臂丛阻滞。对比观察两组的临床效果及药代动力学。结果:与对照组比较,试验组阻滞完善时间及镇痛时间延长(P<0.05或0.01)。试验组与对照组Cmax分别为0.8295±0.2893ug/ml和0.8898±0.2572ug/ml,Tmax分别为37.6018±8.3461分钟和29.3156±11.1991分钟(P>0.05)。药代动力学参数t1/2Ka及K_(21)两组间有显著性差异(P<0.05或0.01)。结论:肾上腺素能延长丁哌卡因的阻滞完善时间、镇痛维持时间及吸收半衰期,但对血药浓度无明显影响。     

碱化布比卡因肌间沟臂丛阻滞的临床效果与药代动力学

对比观察碱化布比卡因和非碱化布比卡因的临床效果及药代动力学。选择ＡＳＡⅠ－Ⅱ级肩部或上肢手术患者１６例，随机分为两组：碱化组与对照组各８例，均用０．７５％布比卡因２ｍｇ／ｋｇ行肌间沟臂丛神经阻滞。     

左旋布比卡因与布比卡因在臂丛神经阻滞中的药效学比较

目的比较左旋布比卡因与布比卡因在臂丛神经阻滞中的药效学特性.方法60例上肢手术患者,ASA Ⅰ～Ⅱ级,随机分成三组,Ⅰ组为0.375%布比卡因,Ⅱ组为0.375%左旋布比卡因,Ⅲ组为0.375%左旋布比卡因加1：200 000肾上腺素.肌间沟法行臂丛神经阻滞.观察阻滞起效时间及持续时间、神经阻滞节段数、术中镇痛质量、不良反应以及注药前、注药后5、10、30、60 min时心率（HR）和平均动脉压（MAP）.结果Ⅱ、Ⅲ组麻醉起效时间短于Ⅰ组（P＜0.05）;麻醉持续时间Ⅱ、Ⅲ组长于Ⅰ组但差异无显著性,Ⅱ、Ⅲ组间比较差异无显著性;各组阻滞节段数、术中牵拉痛发生率、HR及MAP差异无显著性;Ⅰ组寒战发生率高于Ⅱ、Ⅲ组（P＜0.05）.结论左旋布比卡因有与布比卡因相似的药效学特性,可安全用于临床臂丛神经阻滞;肾上腺素不延长左旋布比卡因的麻醉持续时间.     

Pharmacokinetics and pharmacodynamics of vecuronium bromide

The pharmacokinetics and pharmacodynamics of vecuronium bromide were studied in patients under general anesthesia of enflurane and nitrous oxide in oxygen. Eighteen patients were randomly divided into two groups which received either 0.05mg·kg^–1 (low dose group) or 0.20mg·kg^–1 (high dose group) of vecuronium intravenously. The plasma concentration of vecuronium was determined by high performance liquid chromatography. The neuromuscular blocking effect was assessed by measuring the twitch tension of the adductor pollicis muscle elicited by supramaximal electrical stimulation. Pharmacokinetic analysis was carried out using a two compartment model.The relationship between the T4/T1 and T1/ control T1 ratios differed during onset and spontaneous offset of the blockade; the T4/T1 ratios were significantly higher during onset than during offset, although there were large variations of fade in the train-of-four response in each patient during offset. These results suggest that it is difficult to estimate the T1/control T1 ratio by the T4/T1 ratio during offset.Pharmacokinetic analysis revealed that the high dose group had a shorter elimination half-life than did the low dose group. A shorter elimination half-life at a high dose may be to some extent due to hepatic clearance. The pharmacokinetic parameters bore no fixed relationship to the pharmacodynamics in each patient.(Nomura T: Pharmacokinetics and pharmacodynamics of vecuronium bromide. J Anesth 6: 28–37, 1992)     

剖宫产孕妇硬膜外给局麻药的药代动力学

为了解孕妇硬膜外给局麻药的药代动力学，选择２０名实施剖宫产手术的健康临产妇，随机分成硬膜外腔给予了哌卡因组（Ｂ１组）和给予利多卡因组（Ｌ组）。另外， ６例非妊娠患者硬膜外腔给予了哌卡因（Ｂ２组）。Ｂ１和Ｂ２组均给予０．７５％丁哌卡因１～１．５ｍｇ·ｋｇ－１，Ｌ组给予２％利多卡因４～４．５ｍｇ·ｋｇ－１。采用高效液相色谱（ＨＰＬＣ）测定硬膜外给药后血浆药物浓度。结果表明三组病例血药浓度均在安全范围内。Ｂ１组的血药浓度达高峰时间（Ｔｐｅａｋ）和脐静脉与母体血药浓度比（ＵＶ／ＭＶ）值均小于Ｌ组，表明丁哌卡因在硬膜外腔的吸收比利多卡因快，且透过胎盘屏障的药量小于利多卡因，新生儿Ａｐｇａｒ评分在娩出后５分钟均为１０分。Ｂ１组的药代动力学参数与Ｂ２组基本相似。结论：剖宫产手术硬膜外腔给予临床剂量的局麻药是安全的。     

罗比卡因用于小儿骶管阻滞时的药代动力学特征

目的 研究罗比卡因用于幼儿骶管阻滞时药代动力学特征,为临床应用提供理论依据。方法 选择先天性巨结肠根治术患儿14例,随机分为两组,在骶管阻滞时分别注入0.25％罗比卡因0.75 ml/kg或0.2％布比卡因0.75 ml/kg。用气相色谱法测定血浆药物浓度,并监测呼吸和循环指标,观察麻醉效果。结果 罗比卡因和布比卡因的药-时曲线均符合一室开放模型,t_(1/2)分别为0.16h和0.11h,T_(peak)分别为0.53h和0.49h,C_(max)分别为0.81mg/L和1.08mg/L。另外发现其主要药代动力学参数、血药浓度-时间曲线下面积(AUC)分别为2.0 mg·L~(-1)·h~(-1)和3.9mg·L~(-1)·h~(-1),t_(1/2)β分别为1.21h和2.2h,总清除率(CL)分别为567 ml/min和287 ml/min,两组间均有显著差异(P<0.05);呼吸、循环各指标均平稳,麻醉效果满意。结论 罗比卡因比布比卡因较少发生中枢神经系统及心血管的蓄积,用于小儿骶管阻滞是安全可行的。     

Pharmacokinetics and pharmacodynamics of mycophenolic acid in stable renal transplant recipients treated with low doses of mycophenolate mofetil

Abstract Suboptimal doses of mycophenolate mofetil (MMF) are frequently employed in renal transplant (Tx) patients, with drug‐related side effects or low weight. The aim of this study was to compare the mycophenolic acid (MPA) pharmacokinetic profile and its pharmacodynamic effect on patients receiving either standard (2 g) or low (1.5 g or 1 g) MMF doses, in order to evaluate the therapeutic efficacy of such low doses in inhibiting IMPDH activity. Twenty‐seven stable renal Tx recipients aged 18‐65 years, with a post‐Tx follow‐up of 38.5 ± 44.8 months (6‐166 months), receiving 1 g (n = 10), 0.75 g (n = 7) and 0.5 g (n = 10) MMF twice a day in association with cyclosporine and prednisone, were included. The control group was made up of untreated healthy volunteers (n = 5). Plasma concentrations of MPA were analyzed by reverse‐phase HPLC. IMPDH activity was determined in lymphocytes by the measurement of ³H release from [2,8‐³H] hypoxantine. The mean value of areas under the concentration‐time curves (AUC_0‐12) of MPA throughout the 12‐h dosing interval in patients treated with 2 g was higher than the corresponding data in patients receiving 1.5 g or 1 g bid, but no statistical differences were observed between the three groups. There was no correlation between MPA‐AUC_0‐12 values and MMF dose (expressed in g/day or g/kg per day). Predose MPA concentrations correlated only weakly with the respective MPA‐AUC_0‐12 values (r² from 0.385 to 0.655), whereas an acceptable correlation was observed between MPA C_max and MPA‐AUC_0‐12 (r² from 0.626 to 0.759) in 2 g, 1.5 g, and 1 g MMF groups. An inverse relationship between MPA concentrations and IMPDH activity was observed. In general, the maximum MPA concentration was achieved from 1 h to 2 h after dosing, and the maximum inhibition of IMPDH was also from 1 h to 2 h after dosing. The evaluation of IMPDH activity demonstrated that there was a significant statistical difference between samples from 0 to 1 h (P = 0.008) and 0 to 2 h (P = 0.04). In conclusion, concentration‐time profiles of renal transplant recipients administered 0.75 g and 0.5 g twice a day are slightly lower than those from the 2 g group, but nor significantly. On the other hand, inhibition of IMPDH activity was comparable in the three groups, indicating considerable interindividual pharmacodynamic variability. Pharmacodynamic monitoring of the degree of immunosuppression and its correlation with MPA plasma concentrations will be assessed further in future studies.