氟康唑胶囊的人体生物等效性研究

目的评价广州光华药业股份有限公司研制的氟康唑胶囊(受试制剂)与大连辉瑞制药有限公司生产的氟康唑胶囊(参比制剂)的生物等效性。方法20名健康志愿者随机交叉、单剂量口服氟康唑胶囊被试制剂与参比制剂各150 mg,用高效液相色谱法测定血浆中氟康唑浓度。用3P97药动学软件进行参数计算及生物等效性评价。结果受试制剂和参比制剂的主要药动学参数如下:tmax分别为(1.0±0.7)h和(1.7±0.8)h,Cmax分别为(4.0±1.2)mg.L-1和(3.6±1.3)mg.L-1,AUC0-t分别为(132.4±26.5)mg.h.L-1和(138.4±30.8)mg.h.L-1,AUC0-∞分别为(143.7±26.1)mg.h.L-1和(150.2±33.1)mg.h.L-1。氟康唑胶囊受试制剂的相对生物利用度为(97.9±18.3)%。结论对tmax及经对数转换后的Cmax、AUC0-t进行统计分析、方差分析后进行双单侧t检验及90%可信限判断,两制剂具有生物等效性。     

氟康唑胶囊的人体药动学及其生物等效性研究

目的:研究氟康唑胶囊受试制剂与参比制剂在健康志愿者体内的药代动力学和生物等效性。方法:18名健康男性受试者随机双周期交叉单剂量口服氟康唑胶囊受试制剂和参比制剂200 mg,用HPLC法测定氟康唑的血药浓度,求得有关药动学参数。结果:氟康唑胶囊受试制剂和参比制剂的AUC0~120 h分别为(224.977±39.361)和(211.212±36.221)mg/h.L-1,Cmax分别为(5.811±1.202)和(5.705±1.092)mg/L,Tmax分别为(1.056±0.466)和(1.375±0.884)h,t1/2分别为(32.559±5.072)和(30.162±7.257)h。受试制剂相对于参比制剂的生物利用度(F)为(107.41±14.79)%。氟康唑AUC0~120 h和Cmax经对数转换后双单侧t检验均P>0.05,受试制剂AUC0~120 h90%可信限度在参比制剂100.7%~112.6%内,Cmax 90%可信限度在参比制剂92.8%~111.1%区间内。结论:氟康唑胶囊的受试制剂与参比制剂具有生物等效性。     

氟康唑胶囊的人体生物等效性研究

目的研究氟康唑在人体中药代动力学和生物等效性。方法20名健康志愿者随机交叉口服氟康唑两种制剂(参比制剂与受试制剂)各200mg,采用HPLC法测定血药浓度。血浆中氟康唑的测定采用固相萃取(SPE)-HPLC法,方法的线性范围为0.1～10.0mg.L-1,最小检出浓度为0.05mg.L-1,相对回收率为98.5%～105.0%,日内RSD和日间RSD均≤9.52%。结果参比制剂与受试制剂的Cmax分别为(4.58±0.51)mg.L-1及(4.54±0.58)mg.L-1,Tmax分别为(1.8±1.1)h和(1.7±1.1)h,T1/2分别为(29.2±3.19)h和(29.3±3.34)h,AUC0-120分别为(129.55±22.3)mg.h.L-1和(132.98±25.08)mg.h.L-1,AUC0-∞分别为(137.05±39.00)mg.h.L-1和(140.48±38.41)mg.h.L-1各药动学参数经统计学检验均无显著性差异(P>0.05)。由此算得受试制剂相对于参比制剂的F为103%±11.9%。结论氟康唑两种制剂在健康人体中的吸收速度和吸收量差异无显著性意义,两药具有生物等效性。     

枸橼酸喷托维林口腔崩解片人体生物等效性评价

目的 评价枸橼酸喷托维林口腔崩解片在健康男性受试者体内的生物等效性.方法 健康志愿者20名,随机双周期交叉试验设计,单剂量口服25 mg枸橼酸喷托维林受试制剂和参比制剂.用HPLC-MS/ESI+法测定人血浆中枸橼酸喷托维林的浓度.用DAS程序计算药动学参数并评价两种制剂的生物等效性.结果 受试制剂与参比制剂的Tmax分别为(1.62±0.75)h和(2.52±1.21)h;Cmax分别为62.28±33.06μg·L-1和59.72±33.25μg·L-1;AUC0 15分别为234.44±130.01μg·h·L-1和228.77±129.24 μg·h·L-1;AUC0∞分别为246.80±136.19μg·h·L-1和244.11±140.73 μg·h·L-1.Cmax、AUC0 15和ALUC0∞的90%可信区间分别为81.4%～138.4%、86.0%～123.3%和86.5%～121.2%.结论 受试制剂与参比制剂具有生物学等效性.     

氟康唑胶囊的人体药代动力学及其生物利用度比较分析

目的:探析氟康唑胶囊的人体药代动力学及其生物利用度。方法:筛选24例男性健康志愿者分为两组,试验前1 d晚8:00后禁食,试验当日早晨取空白血样,两组志愿者空腹1次口服试验制剂或参比制剂氟康唑胶囊300 mg,按照规定进水、进食,在固定的时间点抽取血样,并且对血样数据进行统计分析。结果:在药代动力学参数方面,Cmax和AUC0-96T在制剂间及周期间差异无统计学意义(P>0.05),但个体间差异较大;在生物等效性评价方面,受试药物的相对生物利用度为98.24%～107.54%,在AUC0-96R90%可信限在参比制剂的80%～125%之间,Cmax(1-2α)的90%可信限在参比制剂的规定范围内;在药剂间及周期间差异均无统计学意义(P>0.05),个体间差异有统计学意义(P<0.01)。结论:受试制剂与参比制剂的氟康唑胶囊生物等效,但个体间差异较大。     

头孢克洛胶囊健康人体药动学及生物等效性研究

目的:研究头孢克洛受试制剂和参比制剂的人体药动学和生物等效性.方法:20名健康受试者随机交叉口服受试制剂与参比制剂,剂量均为500 mg/人.采用HPLC法测定血中头孢克洛的浓度.结果:受试制剂与参比制剂的主要药动学参数Cmax分别为(13.31±3.57) mg/L、(12.81±3.02) mg/L; tmax 分别为(1.01±0.37) h、(0.96±0.31) h;t1/2分别为(0.47±0.25) h、(0.42±0.18) h;AUC0→tn分别为(19.63±3.21) mg·h/L-1、(20.06±2.89) mg·h/L-1.2种制剂的药动学参数相近,以AUC0→tn 计算的受试制剂的相对生物利用度为 (98.68±14.34)% .结论:受试制剂和参比制剂生物等效.     

依诺沙星分散片人体相对生物利用度与生物等效性研究

目的:用研制的依诺沙星分散片与上市的依诺沙星胶囊进行比较,研究它们的人体相对生物利用度,并做出生物等效性评价,以考察试验制剂的药品质量.方法:按照两制剂两周期随机交叉设计,19名男性健康志愿者单剂量口服试验片(100mg×4)和参比胶囊(100 mg×4).采用HPLC-紫外法测定血浆依诺沙星浓度.运用DAS 2.0软件处理血药浓度数据和计算参数,并进行统计学分析,并评价两制剂的生物等效性.结果:单剂量口服400mg的依诺沙星试验片和参比胶囊,测得AUC0→24分别为(21.20±5.78)mg·h-1·L-1、(18.78±3.53)mg·h-1·L-1,AUC0→∞分别为(22.66±6.28)mg·h-1·L-1、(20.09±3.97)mg·h-1·L-1;Cmax分别为(3.66±1.04)mg/L、(3.37±1.05)mg/L;Tmax分别为(1.29±0.69)b、(1.32±0.58)h;t1/2分别为(6.26±1.15)h、(6.08±1.57)h;受试制剂对参比制剂平均相对生物利用度(112.3±21.4)%.结论:依诺沙星分散片与依诺沙星胶囊制剂生物等效.     

奥美拉唑肠溶胶囊人体药代动力学及生物等效性研究

目的 比较2种奥美拉唑肠溶胶囊在健康志愿者体内的药代动力学与生物等效性.方法 20名健康志愿者,采用单剂量、随机、自身交叉对照实验设计,空腹口服奥美拉唑受试和参比制剂各40 mg,用反向高效液相色谱法分别测定血药浓度,用DAS程序进行药代动力学分析,并评价两制剂的生物等效性.结果 受试和参比制剂药代动力学参数AUC0→12、AUC0→∞、Cmax、tmax及t1/2分别为(3497.4±2759.1)、(3726.1±3200.5)μg/L·h-1;(3612.1±2854.6)、(3814.1±3259.1)μg/L·h-1;(1424.1±854.9)、(1421.3±951.6) μg/L;(2.23±0.50)、(2.13±0.60)h;(2.12±1.25)、(2.19±1.27)h,受试制剂的相对生物利用度为(98.2±13.2)%.经交叉实验方差分析,上述药代动力学参数无显著性差异(P＞0.05).结论 两种制剂具生物等效性.     

谷氨酰胺人体生物等效性评价研究

目的评价复方谷氨酰胺两种制剂中谷氨酰胺是否生物等效.方法男性健康受试者24名,随机分成两组,交叉口服受试制剂和参比制剂各1.99 g,在一定时间点取静脉血分离血浆,用高效液相色谱紫外检测法测定人血浆中谷氨酰胺,所得数据经3P97处理得到主要药代动力学参数.结果被试制剂与参比制剂谷氨酰胺的Tmax分别为(1.65±0.63) h和(1.65±0.56) h,Cmax分别为(63.83±14.60)μg/ml和(71.09±16.67)μg/ ml,用梯形法计算所得的AUC0-t分别为(252.74±59.77)μg*h*ml-1和(281.31±82.62)μg*h*ml-1.对Tmax和经对数转换后的Cmax,AUC0-t进行方差分析和双单侧t检验及90%可信限判断,谷氨酰胺Tmax落在参比制剂的85.7%～114.3%范围内,Cmax落在参比制剂的81.4%～98.9%范围内,AUC0-t落在参比制剂的84.7%～97.6%范围内,复方谷氨酰胺颗粒剂的相对生物利用度谷氨酰胺为93.0%±20.2%.结论两制剂中谷氨酰胺生物等效.     

盐酸二甲双胍缓释片人体药代动力学和相对生物利用度研究

目的:研究盐酸二甲双胍缓释片(受试制剂)和普通片(参比制剂)在健康受试者体内的药代动力学过程和相对生物利用度.方法:20名男性志愿者随机自身交叉口服受试制剂和参比制剂,单剂量两制剂各服用1 000 mg,多剂量受试制剂服用1 000 mg×1次/天,参比制剂服用500 mg×2次/天.血浆中二甲双胍浓度使用HPLC-UV法测定.采用二房室模型进行血药浓度-时间数据分析,并计算药动学参数和相对生物利用度.结果:受试制剂和参比制剂单剂量口服后二甲双胍的Cmax分别为(1.61±0.37)μg/ml和(2.47±0.74)μg/ml;Tmax分别为(3.1±0.6)h和(1.5±0.7)h;T1/2分别为(5.1±1.9)h 和(2.7±0.3)h;AUC0→1分别为(11.08±2.88)h·μg/ml和(12.03±2.63)h·μg/ml;受试制剂相对于参比制剂的生物利用度F为(92.6±14.7)%.受试制剂和参比制剂多剂量口服后二甲双胍的Cmax分别为(1.60±0.25)mg/ml和(1.57±0.40)μg/ml;Tmax分别为(3.2±0.4)h和(1.1±0.5)h;T1/2分别为(5.5±3.1)h和(3.0±0.6)h;AUCss分别为(13.24±3.08)h·μg/ml和(6.99±1.50)h·μg/ml.受试制剂的相对生物利用度F为(95.3±17.5)%.结论:受试制剂和参比制剂生物等效,且具有缓释特性.     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.     

Expression of OPGmRNA and ODFmRNA in the patients of hip fracture due to osteoporosis

Objective：To investigate the gene expression of osteoprotegerin（OPG） and osteoclast differentiation factor（ODF） in the bone tissue of patients with hip fracture due to osteoporosis. Methods：OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers（over 50 years old） with hip fracture（Observer Group） and 30 cases of hip facture sufferers with no osteoporosis（Control group） were analyzed with the Semi-Quantitative RT-PCR method. Results：The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion：Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.     

The clinicopathological and immuohistochemical analysis of solid-pseudopapillary tumor of the pancreas： report of 9 cases

Objective：To investigate the clinical features, pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas（SPTP）. Methods：Nine surgically treated cases of SPTP were retrospectively reviewed. Hematoxylin and Eosin（HE） staining and immunohistochemical staining were used to analyze all cases, and the general clinical data was collected. Results：Six patients were asymptomatic except for a palpable mass. Two patients complained of vague-epigastric pain. One patient appeared jaundice. The tumor was encapsulated and solid tissues alternately with cystic tissues. Histologically, the histological structure of solid portion was pseudopapillary with a fibrovascular core. Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns. Immunohistochemical studies demonstrated that SPTP proved positive in vimentin（9/9 cases）, AAT（9/9 cases）, NSE（9/9 cases）, ACT（7/9 cases）, CK20（2/9 cases）, CgA（1/9 cases）, S-100（3/gcases）, PR（4/gcases）, Syn（3/9 cases） and CD56（5/9cases）, negative in CEA and ER. Conclusion：SPTP is a tumor predominantly occurring in young women frequently without special symptoms. This tumor has various characteristical histological patterns with different immunophenotype.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.