盐酸西替利嗪的人体药代动力学研究

目的 :用进口盐酸西替利嗪片 (A)为对照品 ,评价片剂B的相对生物利用度和生物等效。方法 :采用随机交叉分组试验设计 ,10名健康成年男性受试者分别口服单剂量 2 0mg测试品和对照品 ,采用HPLC法测定人血清中药物浓度进行生物等效性的研究。结果 :对照品和测试品的tmax分别为 ( 1 72± 0 39)h和 ( 1 6 5± 0 55)h ,Cmax分别为 ( 6 13± 12 1 7)ng/ml和 ( 597± 119 8)ng/ml,AUC0～ 2 4分别为 ( 2 855 1± 52 8 3)h·ng/ml和 ( 30 16 4± 70 2 8)h·ng/ml,t1/2分别为 ( 11 5± 2 7)h和 ( 12 0±2 9)h ;片剂B相对A的平均生物利用度为 ( 10 0 2± 7 4 ) %。结论 :测试片剂B与对照片剂A具生物等效性     

阿莫西林-克拉维酸钾片剂和干混悬剂的生物等效性

目的 :研究阿莫西林 克拉维酸钾片剂和干混悬剂在健康志愿者中的生物等效性。方法 :2 1名健康男性志愿者随机交叉分别单次空腹服用受试品阿莫西林 克拉维酸钾片剂、干混悬剂以及对照品 (片剂 )各 1次 ,剂量均为阿莫西林 16 0 0mg ,克拉维酸钾 2 2 8mg。以高效液相色谱法测定血浆中阿莫西林和克拉维酸的药物浓度。 结果 :受试者单剂空腹口服受试片剂、干混悬剂和对照片剂后阿莫西林的平均血药峰浓度 (Cmax)分别为 (2 0 .5 6± 3.34)mg/L、(2 2 .5 3± 3.86 )mg/L和 (19.5 3±2 .91)mg/L ,达峰中位时间 (Tmax)分别为 2 .0 0 (1.5 ,4 .0 )h、2 .0 0 (1.5 ,3.0 )h和 2 .0 0 (1.5 ,5 .0 )h ,AUC0 ∞ 分别为 (10 2 .4 8±2 1.83)h·mg/L、(97.76± 18.90 )h·mg/L和 (97.95± 19.77)h·mg/L ;克拉维酸的Cmax分别为 (4.5 8± 1.5 4 )mg/L、(5 .2 5±1.2 0 )mg/L和 (4.6 3± 1.33)mg/L ,Tmax分别为 1.5 (1.0 ,4 .0 )h、1.0 (1.0 ,4 .0 )h和 1.5 (1.0 ,4 .0 )h ,AUC0 ∞ 分别为 (13.70± 4 .0 1)h·mg/L、(14 .0 5± 3.99)h·mg/L和 (13.6 0± 3.5 6 )h·mg/L。 2种受试制剂中阿莫西林的相对生物利用度分别为(10 5 .2 6± 13.73) %和 (10 1.2 0± 16 .5 9) % ,克拉维酸分别为 (10 0 .71± 11.6 2 ) %和 (10 3     

益智药阿尼西坦胶囊在人体内的生物等效性评价

目的:比较两种阿尼西坦胶囊在健康志愿者体内的药动学及生物等效性。方法:18名男性健康志愿受试者,采用标准二阶段交叉设计自身对照试验方法,单剂量口服阿尼西坦胶囊试验品和参比品400mg,以高效液相色谱法测定血浆中阿尼西坦主要活性代谢产物—对甲氧基苯甲酰氨基丁酸(N-anisoyl-GABA,ABA)的经时浓度,对两种阿尼西坦胶囊制剂的主要参数进行统计学比较。结果:两种阿尼西坦胶囊在健康志愿者体内的药-时曲线均符合一级吸收的单室模型,试验品和参比品的主要药动学参数达峰时间Tmax(实测值)、最大血药浓度Cmax(实测值)、曲线下面积AUC0～180min分别为:(28.90±3.23)比(30.00±6.60)min,(11.33±2.49)比(10.64±2.09)mg/L,(801.62±151.88)比(750.21±147.78)mg·min/L(F=0.1607～3.4532,P均>0.05);试验品的相对生物利用度为108.4%。结论:统计学结果显示两种阿尼西坦胶囊制剂具有生物等效性。     

国产头孢泊肟酯胶囊人体生物等效性研究

目的 :评价国产头孢泊肟酯胶囊及进口头孢泊肟酯片剂相比较的生物等效性。方法 :采用双周期随机交叉方法进行试验设计 ,2 0名青年男性健康受试者按体重指数进行随机分层 ,分别服用 2 0 0mg国产头孢泊肟酯胶囊或进口头孢泊肟酯片剂 ,留取静脉血标本 ,以高效液相色谱法测定血药浓度 ,以 3P97程序分析计算药代动力学参数及相对生物利用度 ,判断试验药和对照药的生物等效性。结果 :试验药和对照药的平均血药峰浓度 (cmax)分别为 (3.5 2± 0 .79)mg /L和 (3.75± 0 .6 8)mg /L ,曲线下面积 (AUC)分别为 (2 0 .6 8± 4 .71)mg / (L·h)和 (2 1.18± 4 .5 5 )mg / (L·h) ,达峰时间 (tmax)分别为 (3.18± 0 .88)h和 (3.0 5± 0 .6 3)h ,血浆清除半衰期 (t1/ 2 β)分别为 (2 .4 0± 0 .5 7)h和 (2 .0 2± 0 .4 7)h。两种制剂的药时曲线吻合良好 ,所得主要药代动力学参数经统计学方法检测 ,国产胶囊的AUC1 2α置信区间 (90 % )为 87.4 %～ 10 4 .5 % ,相对生物利用度为 (98.15± 12 .5 8) %。结论 :国产的头孢泊肟酯胶囊与进口头孢泊肟酯片剂为生物等效制剂     

头孢丙烯临床药代动力学和干混悬剂与片剂的生物等效性

目的 :研究头孢丙烯片剂在健康受试者药代动力学和干混悬剂与片剂的生物等效性比较。方法 :10名受试者随机双交叉单次空腹口服头孢丙烯片剂或干混悬剂各 1g后 ,以微生物法测定其血、尿药物浓度。结果 :受试者单次空腹口服头孢丙烯片剂 1g后的血药峰浓度为 (14.5 6± 2 .38)mg/L ,达峰时间为 (1.5 9± 0 .44 )h ,消除半衰期为 (1.18± 0 .2 0 )h ,药时曲线下面积为 (4 6 .30± 6 .6 6 )h·mg/L ,口服片剂者 2 4h累积尿排出率为给药量的 (5 6 .14± 5 .0 8) %。头孢丙烯干混悬剂药代参数与口服片剂者相比 ,两制剂间差异均无显著性 (P >0 .0 5 )。其相对生物利用度为 (10 8.11± 14.78) %。结论 :头孢丙烯片剂体内过程符合血管外二室模型 ,口服后吸收迅速 ,主要经肾脏排出。头孢丙烯干混悬剂与片剂具生物等效性。     

阿莫西林-克拉维酸钾(14:1)颗粒剂生物等效性研究

目的:测定阿莫西-林克拉维酸钾(14:1)颗粒剂生物等效性。方法:18名健康男性志愿者分别采用2制剂、2周期(周期间隔为5 d)双交叉试验方法,口服受试和参比片剂1片(每片含阿莫西林600 mg,克拉维酸钾42.9 mg),采用微生物学方法测定血浆中药物浓度。结果:受试及参比制剂的主要药动学参数分别为:阿莫西林AUCo-sh分别为(25.5±4.12)mg·h/L和(25.0±4.05)mg·h/L;Cmax分别为(9.95±1.45)mg/L和(9.48±1.66)mg/L。克拉维酸钾的AUC0-8h分别为(1.38±0.467)mg·h/L和(1.46±0.508)mg·h/L;Cmax分别为(0.648±0.586)mg/L和(0.586±0.167)mg/L。结论:经统计分析结果显示两制剂生物等效。     

头孢泊肟酯干混悬剂在健康志愿者中的生物等效性

目的:研究头孢泊肟酯干混悬剂在健康人体内的药代动力学及生物等效性。方法:20名受试者随机交叉分别服用头孢泊肟酯干混悬剂(受试制剂)或头孢泊肟酯片剂(参比制剂)各200mg,用微生物法测定人体血浆药物浓度。结果:受试干混悬剂、参比片剂的t_(max)分别为(2.8±0.5)h和(3.1±0.5)h,C_(max)分别为(2.85±0.55)和(2.55±0.62)mg/L。t_(1/2)分别为(2.2±0.2)和(2.3±0.3)h,AUC_(0-t)分别为(16.56±3.96)和(14.79±3.77)mg·h·L~(-1)。受试干混悬剂相对于参比片剂的生物利用度为(115.0±27.1)％。结论:经生物等效性检验,受试干混悬剂与参比片剂具生物等效性。     

盐酸克林霉素胶囊在中国健康受试者的药动学及生物等效性研究

目的研究中国健康受试者中盐酸克林霉素胶囊的药动学,比较国产受试制剂与原研参比制剂的生物等效性。方法采用单中心、随机、开放、单剂量、两周期、两交叉、空腹或餐后给药试验设计,空腹组和餐后组各24名健康受试者口服300 mg盐酸克林霉素胶囊。采用LC-MS/MS法测定血浆克林霉素浓度,Win Nonlin~?6.4版计算药动学参数,并对主要药动学参数进行生物等效性评价。结果无论空腹或餐后给药,服用受试制剂和参比制剂后药时曲线和药动学参数均相似。空腹组参比制剂的C_(max)、T_(max)、AUC_(0-t)、AUC_(0-∞)分别为3.64 mg/L、0.75 h、12.70 h·mg/L、13.10 h·mg/L,受试制剂分别为3.55 mg/L、0.62 h、12.20 h·mg/L、12.40 h·mg/L。餐后组参比制剂的C_(max)、T_(max)、AUC_(0-t)、AUC_(0-∞)分别为3.37 mg/L、2.00 h、15.20 h·mg/L、15.70 h·mg/L,受试制剂分别为3.37 mg/L、2.00 h、16.40 h·mg/L、17.00 h·mg/L。空腹组主要药动学参数C_(max)、AUC_(0-C)、AUC_(0-t)经对数转换后几何均值比(90%CI)分别为99.34%(91.94%～107.34%)、97.84%(90.60%～105.64%)、98.47%(91.28%～106.22%),餐后组分别为99.87%(91.53%～108.97%)、106.28%(98.28%～114.92%)、105.70%(97.81%～114.22%)。经非参数秩和检验,空腹组和餐后组T_(max)差异均无统计学意义(P0.05)。中国健康受试者空腹或餐后口服受试制剂和参比制剂后,C_(max)、AUC_(0-∞)、AUC_(0-t)的几何均值比90%CI均在80.00%～125.00%。结论两制剂在餐后和空腹给药后药时曲线相似,不良事件及发生率均相似。经生物等效性评价,两制剂生物等效。     

阿莫西林分散片与阿莫西林片的药代动力学比较研究

目的建立测定人血浆中阿莫西林浓度的RP-HPLC法,比较阿莫西林分散片与阿莫西林普通片在健康人体内药代动力学差异。方法选择12名男性健康志愿者分为2组,分别单剂量口服阿莫西林分散片与阿莫西林普通片各500 mg,采用高效液相色谱法检测阿莫西林的血药浓度。结果阿莫西林分散片与阿莫西林普通片主要药代动力学参数C_(max)分别为(742.8±68.4)μg/L和(676.7±57.2)μg/L,t_(max)分别为(2.7±0.3)h和(3 4±0.6)h,t_(1/2)分别为(4.9±1.5)h和(5.9±1.8)h,AUC_0~∞分别为(6 417.3±167.5)μg/(h·L)和(4 704.8±117.9)μg/(h·L),AUC_0~1分别为为(4 927.4±119.7)μg/(h·L)和(3436.5±103.5)μg/(h·L)。结论阿莫西林分散片t_(max)、t_(1/2)小于普通片,AUC_0~t、AUC_0~∞、C_(max)高于普通片,说明阿莫西林分散片具有一定的速释优点,明显优于普通片。     

益智药阿尼西坦胶囊在人体内的生物等效性评价

目的：比较两种阿尼西坦胶囊在健康志愿者体内的药动学及生物等效性。方法：18名男性健康志愿受试者，采用标准二阶段交叉设计自身对照试验方法，单剂量口服阿尼西坦胶囊试验品和参比品400mg，以高效液相色谱法测定血浆中阿尼西坦主要活性代谢产物一对甲氧基苯甲酰氨基丁酸(N-anisoyl-GABA，ABA)的经时浓度，对两种阿尼西坦胶囊制剂的主要参数进行统计学比较。结果：两种阿尼西坦胶囊在健康志愿者体内的药-时曲线均符合一级吸收的单室模型，试验品和参比品的主要药动学参数达峰时间Tmax、(实测值)、最大血药浓度Cmax(实测值)、曲线下面积AUC0-180min分别为：(28．90&;#177;3．23)比(30．00&;#177;6．60)min，(11．33&;#177;2．49)比(10．64&;#177;2．09)mg／L．(801．62&;#177;151．88)比(750．21&;#177;147．78)mg&;#183;min／L(F=0．1607～3．4532，P均&;gt;0．05)；试验品的相对生物利用度为108．4％。结论：统计学结果显示两种阿尼西坦胶囊制剂具有生物等效性。     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

Guns and Knives in New Mexico: Patterns of Penetrating Trauma, 1978–1993

Objective: To identify patterns of nonfatal and fatal penetrating trauma among children and adults in New Mexico using ED and medical examiner data.
Methods: The authors retrospectively sampled in 5-year intervals all victims of penetrating trauma who presented to either the state Level-1 trauma center or the state medical examiner from a 16-year period (1978–1993). Rates of nonfatal and fatal firearm and stabbing injury were compared for children and adults.
Results: Rates of nonfatal injury were similar (firearm, 34.3 per 100,000 person-years; stabbing, 35.1). However, rates of fatal injury were significantly different (firearm, 21.9; stabbing, 2.7; relative risk: 8.2; 95% confidence interval: 5.4, 12.5). From 1978 to 1993, nonfatal injury rates increased for children (p = 0.0043) and adults (p < 0.0001), while fatal penetrating injury remained constant. The increase in nonfatal injury in children resulted from increased firearm injury rates. In adults, both stabbing and firearm nonfatal injury rates increased.
Conclusions: Nonfatal injury data suggest that nonfatal violence has increased; fatal injury data suggest that violent death rates have remained constant. Injury patterns vary by age, mechanism of trauma, and data source. These results suggest that ED and medical examiner data differ and that both are needed to guide injury prevention programs.     

手转胎头术失败的原因与分娩结局临床分析

目的 探讨手转胎头术失败的原因与分娩结局.方法 选择2008年1月至2010年12月于我院住院分娩的持续性枕横位、枕后位产妇198例,根据行手转胎头术后结果分为成功组126例、失败组72例.比较两组分娩结局,对比分析失败原因.结果 失败组胎儿体质量≥3500 g的发生率[76.4％(55/72)]明显高于成功组[31.7％(40/126)],差异有统计学意义(x2=30.177,P=0.001)、失败组宫缩乏力发生率[58.3％(42/72)]高于成功组[38.1％ (48/126)],差异有统计学意义(x2=7.569,P=0.006)、失败组骨盆临界或轻度狭窄发生率[38.9％ (28/72)]高于成功组[23.8％(30/126)],差异有统计学意义(x2 =5.030,P=0.002)、失败组手转胎头时机不当(宫口开大＜6 cm、胎头位于坐骨棘上及宫口开大8～10 cm、胎头位于坐骨棘下≥2 cm)发生率[61.1％(44/72)]高于成功组[38.9％(49/126)],差异有统计学意义(x2=9.084,P=0.003).失败组母儿并发症(产后出血、产褥病率、胎儿窘迫、新生儿窒息)发生率高于成功组(x2 =9.586,P=0.002、x2=9.334,P=0.002、x2=5.910,P=0.015、x2=5.240,P=0.022)、失败组剖宫产发生率[72.2％(52/72)]明显高于成功组[34.1 ％(43/126),x2=26.641,P=0.001)].结论 手转胎头术能使难产变顺产,降低剖宫产率,减少母儿并发症,但须积极预防、处理导致手转胎头术失败的原因,对矫正失败后继续矫正及试产应慎重.     

Clinical Pharmacokinetics of Morphine

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/ excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.     

Evidence-Based Pain Management and Palliative Care in Issue Four for 2009 of The Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly. Issue 4 for 2009 contains 4027 complete reviews, 1906 protocols for reviews in production, and 11447 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 600,000 randomized controlled trials, and 12,200 cited papers in the Cochrane methodology register. The health technology assessment database contains over 7500 citations. This edition of the Library contains 90 new reviews, of which 19 have potential relevance for practitioners in pain and palliative medicine.