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。     

尼莫地平在健康人体内的药动学和相对生物利用度

目的 :研究尼莫地平在健康人体内的药动学和相对生物利用度。方法 :8名健康受试者单剂量随机交叉口服尼莫地平标准参比制剂和待测制剂 1 2 0mg,采用HPLC法测定用药后不同时间的血药浓度。结果 :2种制剂的体内过程均符合一房室开放模型 ,AUC分别为 (1 4 3.1± 9.9) μg·h·L-1 和 (1 37.0± 7.3) μg·h·L-1 ,Cmax分别为 (83.1±7.4 ) μg·L-1 和 (80 .8± 4 .6 ) μg·L-1 ,Tmax分别为 (1 .0 0± 0 .0 0 )h和 (1 .0 6± 0 .1 7)h。待测制剂的相对生物利用度为 (96 .0± 5 .9) %。经双向单侧t检验证明 ,2种制剂的AUC、Cmax相比 ,差异均无统计学意义。结论 :2种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。     

盐酸曲马多片剂人体相对生物利用度

目的:研究盐酸曲马多片剂在人体内的相对生物利用度。方法:采用HPLC法测定 18名男性健康受试者单剂量交叉口服 100mg2种盐酸曲马多片剂后不同时间血浆中的药物浓度。结果: 2制剂药 时曲线均符合一房室模型,Cmax分别为(410. 0±71. 1)μg·L-1和 (427. 0±57. 1)μg·L-1,Tmax分别为 (2. 20±0. 49)h和 (2. 20±0. 55)h;T1 /2ke分别为(7. 13±0. 83 )h和 ( 7. 08±0. 74 )h;AUCt0 分别为 ( 4 376±855 )μg·h·L-1和 ( 4 514±1 068)μg·h·L-1,AUC∞0 分别为(5 184±1 112)μg·h·L-1和(5 241±1 330)μg·h·L-1。与参比制剂相比,被试制剂的Ft0 为(98. 94±16. 04)%,F∞0 为(1 101. 90±21. 92)%。结论: 2种制剂具有生物等效性。     

氟康唑胶囊人体生物利用度和生物等效性试验研究

目的 研究氟康唑胶囊的人体相对生物利用度,评价其在健康人体内的药代动力学.方法 20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,用HPLC内标法测定氟康唑的血药浓度,求得有关药代动力学参数.结果 氟康唑胶囊受试制剂和参比制剂的AUC0～96分别为(194.6±38)mg·h·L-1和(197.9±35.63)mg·h·L-1,Cmax分别为(5.46±1.26)mg/L和(5.53±1.12)mg/L,tmax分别为(1.51±0.45)h和(1.39±0.35)h.受试药物的相对生物利用度为94.01%～102.37%,经对数转换后受试药物AUC0～9690%可信限在参比制剂的80%～125%,Cmax(1-2α)的90%可信限在参比制剂的91.39%～105.80%,均在规定范围内.在药剂间及周期间均无显著性差异(P＞0.05),个体间有显著性差异(P＜0.01).结论 氟康唑胶囊的受试制剂与参比制剂生物等效.     

复方氯雷他定缓释片中硫酸伪麻黄碱的人体相对生物利用度和药动学研究

目的研究两种复方氯雷他定缓释片中硫酸伪麻黄碱的相对生物利用度和生物等效性。方法20名健康受试者单剂量和多剂量双交叉口服复方氯雷他定受试制剂和参比制剂,用LC-MS检测法测定血浆中硫酸伪麻黄碱的浓度,并进行相对生物利用度和生物等效性研究。结果单剂量口服2种制剂后,Cmax分别为(404.2±115.5)和(403.6±170.4)ng.mL-1,Tmax分别为(4.8±2.0)和(5.9±1.6)h,AUC分别为(4 115.7±1 490.8)和(3 950.8±1 481.3)ng.h.mL-1,相对生物利用度(106.8±18.7)%。结果显示两制剂硫酸伪麻黄碱的Tmax、Cmax和AUC无显著差异。多剂量口服2种制剂后,Css分别为(343.7±81.4)和(351.3±63.8)ng.mL-1,AUCss分别为(4 124.6±977.1)和(4 215.9±765.7)ng.h.mL-1,DF分别为(1.32±0.26)和(1.26±0.34),相对生物利用度值为(97.9±17.1)%。结论经统计学分析,两种制剂的药动学参数差异无显著性,两制剂的生物利用度相当,具有生物等效性。     

青霉素V钾颗粒剂在健康人体中的药动学及相对生物利用度

目的 :研究青霉素V钾颗粒剂在健康人体中的相对生物利用度 ,评价其生物等效性。方法 :以美国进口的青霉素V钾片为标准参比制剂 ,研究洛阳春都制药公司研制的青霉素V钾颗粒剂相对生物利用度。 10名健康受试者随机交叉口服青霉素V钾被试及参比制剂各 15 0 0mg后 ,采用微生物法测定不同时间血清中药物浓度 ,用3P87软件经微机处理药 时数据。结果 :2种制剂的体内过程均符合二房室开放模型。Cmax分别为 (12 92± 2 2 1)mg·L- 1 和 (12 91± 2 0 4)mg·L- 1 ,Tmax均为 (0 70± 0 11)h ,曲线下面积 (AUC)分别为 (2 0 30± 2 90 )mg·h·L- 1 和 (19 39±2 35 )mg·h·L- 1 。与参比制剂相比 ,被试制剂的相对生物利用度为 (96 0 0± 5 5 6 ) % (86 14%～ 10 5 35 % )。结论 :对2种制剂的AUC、Cmax等进行方差分析、双单侧t检验证明 ,2种制剂具有生物等效性。     

格列吡嗪片在健康人体内的药物动力学及相对生物利用度

目的 :研究格列吡嗪片在健康人体的药物动力学及相对生物利用度。方法 :9名健康受试者单剂量随机交叉口服格列吡嗪片参比制剂和被试制剂 5mg ,采用HPLC法测定用药后不同时间的血药浓度。 结果 :2种制剂的体内过程均符合一房室开放模型 ,Tmax分别为 (3 .67± 0 .50 )h和 (3 .33± 0 .50 )h。Cmax分别为 (391± 37) μg·L- 1和 (40 0± 35) μg·L- 1 ,AUC分别为 (2 .46± 0 .39) μg·h·L- 1 和 (2 .2 3± 0 .88) μg·h·L- 1 ,被试制剂的相对生物利用度为 (1 0 2 .9± 1 5 .7) %。结论 :用NDST软件对两种制剂的AUC、Cmax、Tmax进行双单侧t检验 ,证明两种制剂具有生物等效性。     

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.     

氯雷他定口腔崩解片人体生物等效性研究

目的 对国产氯雷他定口腔崩解片和进口普通片进行生物等效性研究.方法 20名健康男性志愿者按2×2交叉试验方案设计,分别口服受试制剂和参比制剂各20 mg,并采集36 h内动态血标本;采用HPLC/MS测定血浆中氯雷他定浓度,计算药动学参数,并判定两种制剂是否生物等效.结果 受试制剂和参比制剂的主要药动学参数ρmax分别为(19.57±11.09)和(18.97±10.76)μg·L-1,tmax分别为(0.8±0.2)和(0.8±0.2)h,AUC0-36分别为(44.9±17.6)和(42.9±14.6)μg·h·L-1,AUC0-∞分别为(52.6±24.2)和(50.2±19.6)μg·h·L-1,t1/2(ke)分别为(13.1±6.3)和(13.9±6.8)h,两制剂主要药动学参数经对数转换后进行方差分析及双单侧t检验,并计算90%置信区间,表明两种制剂生物等效,受试制剂的人体生物利用度为(103.2±9.0)%.结论 两种制剂生物等效.     

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.     

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.     

Scientific principles and rigorous processes should be followed in developing clinical guidelines for therapeutic interventions of integrative medicine

A clinical guideline for the therapeutic interventions of integrative medicine may be defined as a written document which states a series of recommendations on therapeutic interventions of integrative medicine for a special disease or condition. The guideline may provide assistance to medical professionals in making clinical decisions aimed at improving the clinical outcome of patients and reducing the costs of medical care（~＇4~. Recommendations issued by a guideline should be based on the best available evidence in both Western and Chinese medicine. For fulfilling this purpose, the development of clinical guidelines for therapeutic interventions in the field of integrative medicine should follow scientific principles and undergo a rigorous processes.