注射用紫杉醇纳米乳剂和紫杉醇注射液在比格犬体内的药代动力学比较

目的:建立高效液相-质谱联用法测定比格犬血浆中紫杉醇的浓度,评价和比较注射用紫杉醇纳米乳剂和市售紫杉醇注射液在比格犬体内的药代动力学性质.方法:采用随机、双周期、自身交叉实验设计,比格犬分别匀速静脉滴注40 mg/犬注射用紫杉醇纳米乳剂和紫杉醇注射液.高效液相-质谱联用法测定血浆中药物浓度,并测定药代动力学数据.结果:分别静脉滴注紫杉醇两种制剂后, 比格犬的血药浓度速率下降较快, 两种制剂均为二室模型.注射用紫杉醇纳米乳剂与紫杉醇注射液两种制剂的主要药代动力学参数如下:t1/2z 为(5.07±1.30)和(4.62±0.976)h;Clz为(15.1±2.43)和(10.1±2.35)h·L-1;Vz为(111±38.8)和(65.8±16.4)L;Cmax为(1 416±162)和(2 231±519)μg·L-1;AUC0-680 min为(2 442±535)和(3 753±771)μg·h·L-1; AUC0-∞为(2 725±559)和(4 163±922)μg·h·L-1.结论:两种制剂主要药代动力学参数中AUC,Clz,Vz和Cmax间存在显著性差异(P<0.05),紫杉醇纳米乳剂与紫杉醇注射液的平均AUC之比(纳米乳剂/紫杉醇注射液)为0.665±0.146.     

双靶标新药YL-0919在比格犬体内的药代动力学研究

目的研究5-HT1A受体激动和5-HT重摄取抑制双靶标新药YL-0919在比格犬体内多次给药的药代动力学。方法比格犬按1.5 mg.kg-1剂量灌胃给药,第1天和第5天各给药1次,第2～4天每天给药2次。采用LC-MS/MS法测定血浆中YL-0919浓度,用DAS 2.0软件计算药动学参数。结果首次和末次口服YL-0919(1.5 mg·kg-1)后,主要药代动力学参数为:Cmax分别为(287.73±106.50)和(220.07±58.90)ng·ml-1;tmax分别为(1.10±0.55)和(0.95±0.67)h;t1/2z分别为(3.28±0.85)和(3.02±1.20)h;MRT(0～24)分别为(4.16±0.59)和(3.81±1.22)h;AUC(0～24)分别为(1242.10±462.27)和(922.29±345.29)ng·h·ml-1;AUC(0～∞)分别为(1251.23±464.03)和(938.57±350.30)ng·h·ml-1;CLz/F分别为(1.41±0.74)和(1.95±1.23)L·h-1·kg-1;Vz/F分别为(6.43±2.79)和(7.11±1.90)L·kg-1。经配对t检验,多次给药达稳态后除AUC(0～24)和AUC(0～∞)降低外,其余药动学参数差异均无统计学意义。结论 YL-0919在比格犬体内多次给药后无明显蓄积作用。     

注射用氨苄西林钠在肝硬化病人的药代动力学研究

采用荧光分光光度法测定氨苄西林血药浓度,对氨苄西林在9例肝硬化病人的药代动力学进行了研究。结果表明,iv 3g注射用氨苄西林钠后,药一时曲线符合一室模型。T_(1/2)为1.78±1.54h,Vd为0.586±0.206L/kg,CL为328.0±197.3ml·h~(-1)·kg~(-1)。     

氟氯西林钠胶囊在中国健康人体的药代动力学

目的研究健康受试者单次口服氟氯西林钠胶囊的药代动力学特征。方法健康受试者24名,按3×3拉丁方设计,分别单次口服氟氯西林钠胶囊0.25、0.5、1 g后,采用HPLC法测定血浆中氟氯西林的浓度。用DAS软件程序进行数据处理,用SPSS软件对不同性别药代动力学参数进行统计分析,求算药代动力学参数。结果 3个不同剂量组氟氯西林的主要药代动力学参数:Cmax分别为(8.29±0.51)、(15.93±4.21)、(30.62±9.63)μg/ml,tmax分别为(0.96±0.05)、(0.93±0.07)、(1.03±0.06)h,t1/2分别为(1.24±0.06)、(1.53±0.29)、(1.55±0.28)h,AUC0-10分别为(30.52±9.17)、(60.64±13.26)、(118.39±19.38)μg.h/ml,CL/F分别为(9.03±0.61)、(9.61±0.84)、(9.52±0.82)L/h。各剂量组的C max、AUC0-10、AUC0-∞随剂量的增加而呈比例的增大,各组的Ka、Ke、tmax、t1/2、CL/F等无显著性差异。结论口服不同剂量的氟氯西林钠胶囊,健康受试者体内具有线性药代动力学特征,药代动力学过程符合二室开放模型。     

阿德福韦酯胶囊在健康人体的药代动力学研究

目的 研究阿德福韦酯胶囊在健康人体的药代动力学,计算其参数,为临床给药剂量和间隔时间提供参考依据.方法 8名健康志愿者自身对照,分别单次及多次口服阿德福韦酯胶囊,采用色谱-质谱联用(LC/MS/MS)方法测定其活性代谢产物阿德福韦的血药浓度.结果 单次及多次口服阿德福韦酯胶囊后,其活性代谢产物阿德福韦的Cmax分别为(27.560±10.836)、(27.271±6.695)μg · L-1;Tmax分别为(1.75±0.267)、(1.688±0.259)h;AUC(0-24)分别为(161.798±51.324)、(173.486±38.359)μg · h · L-1;AUC0-∞分别为(170.582±57.067)、(185.713±45.058)μg · h · L-1;吸收速率常数Ka分别为(1.019±0.252)、(1.081±0.377)h-1;消除速率常数K10分别为(0.324±0.105)、(0.307±0.127)h-1;消除半衰期t1/2β分别为(7.117±1.345)、(8.044±2.489)h;清除率CL/F分别为(61.994±18.628)、(55.854±11.794)L · h-1;表观分布容积V/F分别为(218.998±122.07)、(203.457±76.736)L.单次给药和多次给药的主要药代动力学参数经配对t检验均无统计学差异.试验过程中未发现任何不良反应.结论 单次和多次口服阿德福韦酯胶囊后各药动学参数无显著性差异,提示该给药方式连续多次给药时未出现蓄积现象.     

痛风饮中橙皮苷 儿茶素和芒果苷在大鼠体内药代动力学实验

目的研究痛风饮中有效成分橙皮苷、儿茶素和芒果苷在大鼠体内药代动力学。方法采用HPLC法,测定SD大鼠灌胃给予痛风饮后不同时间橙皮苷、儿茶素和芒果苷的血药浓度,采用DAS 2.0软件计算3种成分的药物代谢动力学参数。结果橙皮苷在0.13².67μg·ml^-1呈线性关系,药动学参数:C_max为（22.40±0.22）μg·ml^-1,T_max为1 h,AUC_0-t为（155.11±1.36）mg·L^-1·h;芒果苷在0.17³.44μg·ml^-1呈线性关系,药动学参数:C_max为（12.13±0.18）μg·ml^-1,T_max为2 h,AUC_0-t为（181.84±1.51）mg·L^-1·h;儿茶素在0.08¹.65μg·ml^-1呈线性关系,药动学参数:C_max为（18.00±0.26）μg·ml^-1,T_max为10 h,AUC_0-t为（248.66±1.55）mg·L^-1·h。结论大鼠单次灌胃痛风饮后,橙皮苷、儿茶素和芒果苷体内过程均呈二室模型。     

盐酸川芎嗪透皮贴剂药代动力学研究

目的建立SD大鼠盐酸川芎嗪（TMPH）贴剂和灌胃给药后体内血药浓度的测定方法,计算贴剂组和灌胃组的药代动力学参数并进行比较。方法贴剂组：自制贴剂,SD大鼠背部给药（1.04 g/kg）,分别于给药后0.5、1.5、3、4、5、6、7、8、9、12、17、24 h从尾部静脉取血;灌胃组：SD大鼠灌胃给药（1.6 mg/kg）,分别在给药后5、8、10、13、15、21、34、45、61 min从尾部静脉取血;用HPLC测定两组大鼠体内TMPH的血药浓度,用DAS软件计算。结果灌胃组药代动力学参数：Tmax=0.167 h,Cmax=1.97 mg/L,T1/2=0.076 h,Auc0-t=0.597[（μg·h）/ml],Auc0-∞=0.650[（μg·h）/ml];贴剂组药代动力学参数：Tmax=5.917 h,Cmax=253 mg/L,T1/2=5.95 h,Auc0-t=3547.56[（μg.h）/ml],Auc0-∞=4132.47[（μg.h）/ml]。结论 TMPH灌胃给药时,达峰时间和半衰期都很短,说明TMPH普通制剂在体内吸收代谢非常迅速,难以长时间维持有效血药浓度;TMPH贴剂给药的达峰时间和半衰期大大延长,能够在较长时间内维持较高的血药浓度。     

LC-MS/MS法研究左旋去甲基苯环壬酯在比格犬体内的生物利用度

目的评价左旋去甲基苯环壬酯在比格犬体内生物利用度。方法 LC-MS/MS法测定比格犬口服和静脉给药后体内的血药浓度,计算药代动力学参数和绝对生物利用度。结果比格犬口服给药2 mg/kg后5 min即可测得血中药物含量,口服给药后1 h左旋去甲基苯环壬酯在比格犬体内血药浓度达峰,给药后36 h血中药物浓度均已降至LLOQ以下。比格犬口服和静脉注射2 mg/kg左旋去甲基苯环壬酯的t1/2分别为(5.36±0.82)h和(6.73±2.00)h,Cmax分别为(141.88±51.03)和(591.84±144.61)μg/L;AUC(0-36 h)分别为(962.42±220.96)和(1572.06±365.80)μg.L-1.h;用AUC(0-36 h)计算比格犬口服单剂量左旋去甲基苯环壬酯的绝对生物利用度为(61.22±10.78)%。结论左旋去甲基苯环壬酯口服给药吸收迅速,绝对生物利用度较高,具有良好的开发前景。     

利巴韦林注射液大鼠体内药代动力学研究

目的研究利巴韦林注射液在大鼠体内的药代动力学,并考察利巴韦林的红细胞蓄积情况。方法采用反相HPLC法测定了大鼠静脉注射利巴韦林注射液后利巴韦林的血药浓度,使用3p87药代动力学软件计算其药代动力学参数。结果利巴韦林注射液在大鼠体内符合二室模型,主要的药动学参数如下:T1/2(α)为(10.82±2.66)min,T1/2(β)为(180.0±27.69)min,AUC为(1109.0±212.0)mg·L-1·min,CL(s)为(0.032±0.009)kg·L-1·min-1。结论利巴韦林在红细胞中有大量蓄积。     

尼可胺在大鼠体内的药代动力学研究

目的 采用高效液相色谱法（HPLC）研究尼可胺在大鼠体内的药代动力学变化。 方法 色谱柱为Sino chrom BDS柱（250 mm×4.6 mm,5 μm）,流动相为甲醇-0.02%醋酸（10:90）,检测波长为260 nm,柱温为30 ℃,流速为1 ml/min,进样量为5 μl。通过大鼠眼底静脉取血,血浆经乙腈沉淀蛋白,测定尼可胺血药浓度,通过DAS2.0计算其药代动力学参数。 结果 尼可胺的线性范围：20~1000 μg/ml（r=0.9998）。当尼可胺在大鼠血浆中的浓度为50、150和500 μg/ml时,提取回收率分别为84.9%、81.9%和79.1%,批内精密度和批间精密度均＜5%。当大鼠给予125 mg/kg的尼可胺后,其主要药代动力学参数为：消除相半衰期（t1/2β）为（32.99±23.14）min,血药-时间浓度曲线下面积（AUC）（0-t）为（14390.23±2584.02）mg·L-1·min,AUC（0-∞）为（16569.89±3450.31）mg·L-1·min,达峰时间（Tmax）为（27.0±6.7）min,药峰浓度（Cmax）为（242.13±33.89）mg/L。当大鼠给予250 mg/kg的尼可胺后,其主要药代动力学参数为：t1/2β为（59.05±16.34）min,AUC（0-t）为（26752.23±7967.03）mg·L-1·min,AUC（0-∞）为（35812.87±9476.48）mg·L-1·min,Tmax为（27.5±11.3）min,Cmax为（316.32±63.68）mg/L。当大鼠给予500 mg/kg的尼可胺后,其主要药代动力学参数为：t1/2β为（69.06±0.62）min,AUC（0-t）为（77306.48±27878.03）mg·L-1·min,AUC（0-∞）为（88014.22±26960.89）mg·L-1·min,Tmax为（40.0±7.7）min,Cmax为（601.42±147.150）mg/L。 结论 HPLC操作简便、准确、灵敏度高、重现性好,能够用于尼可胺在大鼠体内的药代动力学研究,为人体内尼可胺的药代动力学研究提供了参考。     

Knee injury and Osteoarthritis Outcome Score (KOOS) - validation of a Swedish version

The Knee injury and Osteoarthritis Outcome Score (KOOS) is a self-administered instrument measuring outcome after knee injury at impairment, disability, and handicap level in five subscales. Reliability, validity, and responsiveness of a Swedish version was assessed in 142 patients who underwent arthroscopy because of injury to the menisci, anterior cruciate ligament, or cartilage of the knee. The clinimetric properties were found to be good and comparable to the American version of the KOOS. Comparison to the Short Form-36 and the Lysholm knee scoring scale revealed expected correlations and construct validity. Item by item, symptoms and functional limitations were compared between diagnostic groups. High responsiveness was found three months after arthroscopic partial meniscectomy for all subscales but Activities of Daily Living.     

Endovascular management of carotid-cavernous fistulas

Objective To investigate endovascular treatment of traumatic direct carotid-cavernous fistulas （CCF） and their complications such as pseudoaneurysms. Methods： Over a five-year period, 22 patients with traumatic direct CCFs were treated endovascularly in our institution. Thirteen patients were treated once with the result of CCF occluded, 8 twice and 1 three times. Treatment modalities included balloon occlusion of the CCF, sacrifice of the ipsilateral internal carotid artery with detachable balloon, coll embolization of the cavernous sinus and secondary pseudoaneurysms, and covered-stem management of the pseudoaneurysms. Results All the direct CCFs were successfully managed endovascularly. Four patients developed a pseudoaneurysm after the occlusion of the CCF with an incidence of pseudoaneurysm formation of 18.2% （4/22）. A total number of 8 patients experienced permanent occlusion of the ICA with a rate of ICA occlusion reaching 36.4% （8/22）. Followed up through telephone consultation from 6 months to 5 years, all did well with no recurrence of CCF symptoms and signs. Conclusion Traumatic direct CCFs can be successfully managed with endovascular means. The pseudoaneurysms secondary to the occlusion of the CCFs can be occluded with stent-assisted coiling and implantation of covered stents.     

The acutely limping child

Acute limping may be the result of multiple pathologies in children. The differential diagnosis varies based on the age of the child. Irrespective of age, the initial imaging work-up includes AP and frog leg radiographs of the pelvis and ultrasound; MRI may sometimes be helpful. In children less than 3 years, infections and trauma are most frequent. MRI is the imaging modality of choice when osteomyelitis is clinically suspected. Between the ages of 3 and 10 years, transient synovitis of the hip and Legg-Calvé-Perthes disease are main considerations but infection, inflammation and focal bony lesions are also considered. In children over 10 years, slipped capital femoral epiphysis also is considered.     

Do Balance Board Training Programs Reduce the Risk of Ankle Sprains in Athletes?

Introduction Ankle sprains are the most common musculo-skeletal injury that occurs in athletes,particularly in sports that require jumping and landing on one foot such as soccer,and basketball(1-4).These injuries often result in significant time loss from participation,long-term disability,and have a major impact on health care costs and resources(5-8).     

High Intensity Interval Training:New Insights

KEY POINTS ·High-intensity interval training(HIT)is characterized by repeated sessions of relatively brief，intermittent exercise.often performed with an“a11 out”effort or at an intensity close to that which elicits peak oxygen uptake(i.e.，≥90%of VO2 peak).     

Developmental validation of the PowerPlex(®) ESI 16 and PowerPlex(®) ESI 17 Systems: STR multiplexes for the new European standard

In response to the ENFSI and EDNAP groups’ call for new STR multiplexes for Europe, Promega^® developed a suite of four new DNA profiling kits. This paper describes the developmental validation study performed on the PowerPlex^® ESI 16 (European Standard Investigator 16) and the PowerPlex^® ESI 17 Systems. The PowerPlex^® ESI 16 System combines the 11 loci compatible with the UK National DNA Database^®, contained within the AmpFlSTR^® SGM Plus^® PCR Amplification Kit, with five additional loci: D2S441, D10S1248, D22S1045, D1S1656 and D12S391. The multiplex was designed to reduce the amplicon size of the loci found in the AmpFlSTR^® SGM Plus^® kit. This design facilitates increased robustness and amplification success for the loci used in the national DNA databases created in many countries, when analyzing degraded DNA samples. The PowerPlex^® ESI 17 System amplifies the same loci as the PowerPlex^® ESI 16 System, but with the addition of a primer pair for the SE33 locus. Tests were designed to address the developmental validation guidelines issued by the Scientific Working Group on DNA Analysis Methods (SWGDAM), and those of the DNA Advisory Board (DAB). Samples processed include DNA mixtures, PCR reactions spiked with inhibitors, a sensitivity series, and 306 United Kingdom donor samples to determine concordance with data generated with the AmpFlSTR^® SGM Plus^® kit. Allele frequencies from 242 white Caucasian samples collected in the United Kingdom are also presented. The PowerPlex^® ESI 16 and ESI 17 Systems are robust and sensitive tools, suitable for the analysis of forensic DNA samples. Full profiles were routinely observed with 62.5 pg of a fully heterozygous single source DNA template. This high level of sensitivity was found to impact on mixture analyses, where 54–86% of unique minor contributor alleles were routinely observed in a 1:19 mixture ratio. Improved sensitivity combined with the robustness afforded by smaller amplicons has substantially improved the quantity of data obtained from degraded samples, and the improved chemistry confers exceptional tolerance to high levels of laboratory prepared inhibitors.