目的 建立并验证胺碘酮及其活性代谢产物去乙基胺碘酮(DEA)的复合生理药动学(PBPK)模型,进而预测胺碘酮和DEA在健康人体各组织器官中的分布特征.方法 检索中国知网、ScienceDirect和PubMed等数据库中关于胺碘酮和DEA的理化常数和药动学性质的相关文献,运用GastroPlusTM Version 9.8软件建立、优化并验证胺碘酮静脉滴注或口服给药的健康人体PBPK模型,通过药动学参数预测值和实测值倍数误差评价模型有效性.采用PBPK模型结合药物特异性参数,应用血流灌注限速模式预测胺碘酮及DEA在各组织器官中的分布特征.结果 利用已发表的日本人群静脉滴注给药5 mg/kg剂量组数据进行PBPK建模,然后利用2.5 mg/kg剂量组的实测数据进行模型验证.模型预测的药动学参数值与实测值的比值基本均在0.5～2.0,说明模型可靠.用中国人群单次口服实测数据进行模型验证,模型预测的药动学参数值与实测值的比值均在0.5～2.0,验证模型适合于中国人群.胺碘酮、DEA在肝、肺、心、肾、脂肪等组织中浓度均远高于血浆浓度,其中在脂肪中浓度升高具有明显的滞后效应,消除半衰期很长.结论 通过建立并验证胺碘酮及DEA复合PBPK模型预测发现,胺碘酮、DEA在肝、肺、心、肾、脂肪中的浓度均远高于血浆浓度,且在脂肪组织中浓度升高滞后于其他组织,为进一步评估胺碘酮的临床有效性和安全性提供了药动学依据.

目的 探讨经同期椎动脉造影和冠状动脉造影证实的椎动脉狭窄与冠状动脉狭窄之间的相关性.方法 纳入2014年1月至2015年8月于首都医科大学附属北京安贞医院同时行椎动脉造影和冠状动脉造影的173例患者的临床资料.根据椎动脉狭窄的程度将患者分为椎动脉轻度狭窄组(狭窄＜50％,122例)和椎动脉重度狭窄组(狭窄≥50％,51例),分析椎动脉狭窄的危险因素.根据患者冠状动脉狭窄情况,将冠状动脉狭窄的患者分为冠状动脉轻度狭窄组(狭窄＜70％,58例)和冠状动脉重度狭窄组(狭窄≥70％,115例),分析冠状动脉狭窄的危险因素.对患者椎动脉和冠状动脉狭窄的具体情况进行统计分析,并探讨二者之间的相关性.结果 统计结果显示年龄、男性、高血压、冠心病(冠状动脉粥样硬化性心脏病)是椎动脉狭窄和冠状动脉狭窄的共同危险因素.椎动脉重度狭窄组总的冠状动脉重度狭窄患者比例以及左前降支、左回旋支、右冠状动脉重度狭窄患者比例明显高于椎动脉轻度狭窄组[80.4％(41/51)比60.7％(74/122)、66.7％(34/51)比42.6％(52/122)、47.1％(24/51)比28.7％(35/122)、54.9％(28/51)比32.8％(40/122)],差异均有统计学意义(均P＜0.05).结论 椎动脉狭窄和冠状动脉狭窄的危险因素基本相同.椎动脉狭窄和冠状动脉狭窄之间存在统计学相关性,对椎动脉狭窄的筛选可以为冠状动脉评估提供依据.

目的 研究阿托伐他汀钙片仿制药与原研药在中国健康男性中单剂量空腹给药的药代动力学和生物等效性,为临床使用和一致性评价提供依据.方法 采用空腹给药、半重复、三周期、交叉、参比药物校正的平均生物等效性试验(RSABE)设计,共纳入36例健康男性受试者,随机分为3组进行重复服用参比药物、三周期、交叉试验,每周期单剂量口服阿托伐他汀钙片20 mg,给药前和给药后按时采集静脉血,以HPLC-MS/MS法测定血浆中阿托伐他汀、邻羟基阿托伐他汀、对羟基阿托伐他汀的浓度,用WinNonlin 6.3计算药代动力学参数并进行生物等效性评价.结果 阿托伐他汀AUC0-t、AUC0-∞均CVWR＜ 30％,用ABE的判断标准,受试药物与参比药物药代动力学(PK)参数几何均数平均值(GMR)估计值的90％置信区间分别为94.8％ ～ 104.4％和94.9％～104.5％,均不超出80.0％ ～ 125.0％;Cmax的CVWR＞30％,用RSABE的判断标准,critbound=-0.049＜0,pointest=0.94不超出0.80～1.25,可以判断受试药物和参比药物的阿托伐他汀具有生物等效性.邻羟基阿托伐他汀和对羟基阿托伐他汀的AUC0-t、AUC0-∞和Cmax的GMR点估计值均在80.0％ ～ 125.0％,可进一步支持受试药物和参比药物具有生物等效性的判断.结论 国产阿托伐他汀钙片和进口阿托伐他汀钙片药代动力学生物等效.

目的 建立高效液相色谱-质谱联用法(HPLC-MS/MS)定量测定人血浆中阿雷地平及其主要代谢产物羟基阿雷地平的浓度.方法 人血浆样品用液液萃取法处理,用Kinetex C18柱(4.6 mm×100 mm,2.6 μm)色谱柱,以纯水-乙腈溶液为流动相,流速为0.5 mL·min-1,用电喷雾离子化源,负离子方式,多反应监测(M RM)扫描方式进行监测.考察该方法的专属性、标准曲线与定量下限、精密度与回收率、基质效应和稳定性.结果 血浆中阿雷地平的标准曲线方程为y=4.45×10-1x +6.6×10-3(r =0.998 2),在0.02～10 μg·L-1线性关系良好,定量下限为0.02 μg·L-1;羟基阿雷地平的标准曲线方程为y=9.82×10-1x+ 1.70 × 10-3(r =0.996 7),在0.2～100 μg·L-1线性关系良好,定量下限为0.2 μg·L-1.2种化合物的日内、日间RSD均＜10％,提取回收率为91.78％～97.97％,无明显的基质效应.结论 本法快速、准确、灵敏度高、重现性好,适用于人体血浆中阿雷地平、羟基阿雷地平浓度的测定,可用于阿雷地平、羟基阿雷地平的药代动力学研究.

OBJECTIVE:To investigate the clinical features of valvular lesions in Takayasu's arteritis.METHODS:We analyzed 22 medical records of patients with Takayasu's arteritis and valvular lesions in Anzhen Hospital, Capital Medical University from January 2012 to January 2015.RESULTS:The spectrums of valvular involvements were aortic valve regurgitation (11, 50%), aortic valve stenosis (1, 4.5%), mitral valve regurgitation (1, 4.5%), mitral valve stenosis (1, 4.5%) and multiple valvular diseases (7, 36.5%).64.7% of patients with aortic valve regurgitation had aortic root dilation.Heart failure was the most common manifestation (63.6%). Glucocorticoid and/or immunosuppressant were administrated on 11 (50%) patients.One (4.5%) patient received Tocilizumab injection.Surgeries were performed on 12 (54.5%) patients with cardiac architecture.Reversible changes in cardiac structure were found by echocardiography within one week after surgery (P<0.05). Three patients died during 10-46 month follow-up, with none of whom taking any anti-inflammatory treatments.CONCLUSIONS:Aortic regurgitation is the prominent valvular lesion in Takayasu's arteritis, mostly secondary to aortic root dilation.Operation could block myocardium reconstruction promptly.The early surgical complication is rare, while perivalvular leakage may occur during longstanding follow-up.Poor inflammatory control might lead to poor long-term outcome.

Objective To compare the pharmacokinetic profiles between a new generic and a branded reference formulation of isosorbide -5 -mononitrate sustained release capsules , and to assess the bioequivalence of the two products in healthy Chinese male subjects.Methods Fifty subjects participated in the open -label, randomized -sequence, 2-way crossover study.Twenty-four subjects and 26 subjects were ran-domly assigned in a 1:1 ratio to receive single dose (50 mg) or multiple dose (50 mg, qd, 6 days) of the test or reference formulation , followed by a one -week washout period and administration of the alternate formulation , respectively.Serial blood samples were collected , and isosorbide -5 -mononitrate concentration in plasma was determined by LC-MS/MS.The relative bioavailability and related parameters of pharmacokinetics were calculated. Results The pharmacokinetic parameters of test formulation and the reference formulation after a single dose were as follows: Cmax were ( 554.18 ± 117.84 ) and (526.29 ±91.58 )μg· L-1; AUC0-t were ( 7834.21 ±1227.70 ) and&nbsp;(7658.86 ±927.74) h· μg· L-1 , respectively.The 90% confidential interval of Cmax and AUC0-t of test formulation were 99.82%-113.03%and 99.13%-106.43%of reference formulation , respectively.The pharmacokinetic parame-ters of test formulation and the reference formulation after multiple doses were as follows :Cmax were (612.96 ±171.32) and (527.12 ±114.36 ) μg · L-1; AUC0-t were ( 8408.71 ±1321.91 ) and ( 7781.88 ±1325.12 ) h · μg · L-1 , respectively.The 90% confidential interval of Cmax and AUC0-t of test formulation were 108.44% -122.17% and 105.35%-111.57% of reference formulation , respectively.The 90% confidence interval of Cmax and AUC0-t of isosorbide-5-mononitrate for the test formulation after single and multiple oral doses were fall within 70%-143%and 80%-125%of reference formulation.Conclusion The test formulation was considered bioequivalent to the reference formulation.

Background: Pilsicainide hydrochloride is a class IC antiarrhythmic agent used for the treatment of supraventricular and ventricular arrhythmias and atrial fibrillation.Objective: The objective of the present study was to determine the pharmacokinetics (PK) of a pilsicainide hydrochloride injection in healthy Chinese adults. The study was conducted to meet China State Food and Drug Administration requirements for the marketing of the new generic formulation of pilsicainide hydrochloride.Methods: This Phase I, randomized, parallel-group, open-label, single-dose PK study was conducted in healthy Chinese volunteers. Subjects were randomized to receive a single dose of 0.25-, 0.50-, and 0.75-mg,/kg pilsicainide hydrochloride with a 10-minute intravenous infusion. Serial blood and urine samples were collected up to 24 hours after dosing; drug concentrations in plasma and urine were then determined by using LC-MS/MS. The PK parameters of pilsicainide were calculated from the plasma concentration time data according to noncompartmental methods. Safety profile was evaluated by monitoring adverse events, clinical laboratory parameters, and the results of 12-lead ECGs.Results: Thirty healthy volunteers (mean [SD] age, 28.0 [4.95] years; weight, 59.3 [6.51] kg; height, 165.0 [7.25] cm; body mass index, 21.7 [1.94] kg/m(2)) were randomly divided into 3 groups, each consisting of 5 men and 5 women. After single-dose intravenous administration of 0.25, 0.50, and 0.75 mg/kg of pilsicainide hydrochloride, mean C-max was 0.34 (0.11), 0.54 (0.15), and 1.05 (0.19) mu g/mL, respectively; AUC(0-24) was 0.76 (0.12), 1.61 (0.37), and 2.61 (0.46) h center dot mu g/mL; and AUC(0-infinity) was 0.79 (0.13), 1.71 (0.46), and 2.72 (0.50) h center dot mu g/mL. The ranges for t(1/2Z) CL, and V-Z, were 5.19 to 5.98 hours, 4.73 to 5.44 mL/min/kg, and 2.23 to 0.58 L/kg, respectively. The mean urinary recovery rate within 24 hours was 75.0% (12.0%), 65.0% (19.2%), and 66.4% (14.1%). Men and women had significantly different AUC(0-24) values in the 0.50-mg/kg dose group (P = 0.044), and V-Z showed significant differences between men and women in all 3 dose groups (P = 0.001). According to ECG parameters, PR intervals were significantly prolonged after administration at all 3 doses (P = 0.034, P < 0.001, and P = 0.034); no significant changes were seen in QRS width, QTc interval, or other parameters.Conclusions: Pilsicainide hydrochloride demonstrated linear PK, and the increase in the exposure of pilsicainide (AUC(0-24) and AUC(0-infinity)) was dose proportional after single doses of 0.25, 0.50, and 0.75 mg/kg. All 3 pilsicainide hydrochloride doses were well tolerated in these Chinese volunteers. ChiCTR-ONC-13003546. (C) 2014 Elsevier HS Journals, Inc. All rights reserved.

OBJECTIVE:To verify the application safety of medical anti-adhesion modified chitosan (Baifeimi) in cardiac surgery.METHODS:From August to December 2010, 42 patients undergoing surgery for congenital heart disease, valvular heart disease or ischemic heart disease were selected and divided into testing (n = 22) and control (n = 20) groups. After complete intraoperative hemostasis, two sheets of anti-adhesion modified chitosan (Baifeimi) were placed on the surface of heart and vessels in the testing group and then chest was closed. And the control group underwent routine chest closing without an application of Baifeimi. The systemic and local reactions and drainage fluid were observed. The postoperative drainage fluid was subject to bacteria culture. Blood routines and laboratory tests at preoperation and Day 1 and Week 1 postoperation were performed to evaluate the changes of chemical, biological and immunological parameters.RESULTS:There was no occurrence of systemic reaction, local inflammation or exudation.Wounds were healed at Phase I. The drainage fluid of pericardium and mediastina had no significant intergroup difference. Drainage was unobstructed in the testing group. A comparison of two groups revealed that the differences of aspartate aminotransferase ( (24 ± 17) vs (40 ± 22) U/L), preoperative and postoperative immunoglobulin A( (1.9 ± 0.7) vs (2.9 ± 1.4) g/L, (2.3 ± 0.9) vs (3.3 ± 1.5) g/L) were statistically significant (all P < 0.05). But the average values of both group stayed within a normal range without clinical significance while other indices had no significant difference. The bacteria cultures of all patients in the control group were negative.CONCLUSIONS:Anti-adhesion modified chitosan is both convenient and safe for clinical application. The duration of cardiac surgery is not extended.No systemic or local adverse event is reported. There is no interference of hepatic, renal or immune functions.

OBJECTIVE To develop a sensitive and specific LC-MS /MS method for the determination of pilsicainide in human plasma and urine. METHODS The samples were processed by LLE( liquid-liquid extraction),acetonitrile-ammonium acetate( 0. 1‰ formic acid)-water was used as the mobile phase with isocratic elution( 25∶ 37. 5∶ 37. 5 in plasma,35 ∶ 6 ∶ 59 in urine),and separation was carried out on Welch Material Ultimate AQ-C18column( 2. 1 00 × 100 mm,3. 5 μm),setting the flow rate as 0. 35 mL·min-1,the column temperature at 25 ℃. The injection volume was 5 μL. ESI under positive ion mode and multiple reaction monitoring scan( MRM) were used for quantitative analysis with m / z 273. 4→110. 2 for pilsicainide and m/z 287. 4 →110. 2 for internal standard,methyl-pilsicainide. RESULTS The linear ranges of the calibration curves for pilsicainide were 1-1 200 μg·L-1for plasma and 1-150 mg·L-1for urine. The limitation of detection were 1 μg·L-1for plasma and 1 mg · L-1for urine. The correlation coefficient was between 0. 996 2 and 0. 999 1. The extraction recoveries,matrix effects,and intra-/ inter-assay precisions all met the requirements of pharmacokinetic studies. This approach was applied to determine pilsicainide concentrations in human plasma and urine in a clinical pharmacokinetic research. CONCLUSION This approach possesses convenience,accuracy,high sensitivity and good reproducibility,which can meet the requirements of pharmacokinetic studies.

目的:研究中国健康受试者单次和多次口服阿雷地平(AR)肠溶胶囊后阿雷地平(AR)及其主要代谢产物羟基阿雷地平(AR-M1)的药代动力学特征。方法:36名健康受试者,随机分为3组,平行单次口服5,10和20 mg阿雷地平肠溶胶囊的药代动力学研究,10 mg组受试者继续进行多次口服10 mg,qd,连续7 d的药代动力学研究,采用LC-MS/MS法测定血浆中阿雷地平及其主要代谢产物AR-M1的药物浓度,采用DAS 2.1.1软件计算药代动力学参数。结果:单次口服阿雷地平肠溶胶囊5～20 mg后阿雷地平和AR-M1的消除半衰期(t1/2z)分别约为2.0～2.7 h和3.9～5.6 h;达峰浓度(Cmax)随剂量增加呈线性增加,分别为[(2.12±1.14)～(11.34±5.98)μg.L-1]和[(29.41±9.80)～(111.74±24.03)μg.L-1];血药浓度-时间曲线下面积(AUC)也随剂量增加呈线性增加,阿雷地平和AR-M1的AUC0～t分别为[(6.02±2.96)～(30.33±8.88)μg.h.L-1]和[(156.05±32.24)～(776.00±160.47)μg.h.L-1],AUC0～∞分别为[(6.12±2.98)～(30.53±8.89)μg.h.L-1]和[(159.39±33.23)～(785.53±161.92)μg.h.L-1]。多次口服阿雷地平肠溶胶囊10 mg后阿雷地平和AR-M1的t1/2z分别约为2.5和5.5 h,AUC0～t分别为(18.09±5.42)和(604.46±159.66)μg.h.L-1,AUC0～∞分别为(18.25±5.42)和(611.93±162.81)μg.h.L-1。结论:在5～20 mg剂量范围内阿雷地平和AR-M1呈线性药代动力学特征,10 mg多次给药,阿雷地平和AR-M1的Cmax和AUC均较单次给药显著增加,但未见明显蓄积。

Objective To study pharmacokinetic and pharmacodynamic characteristics of homemade bivalirudin in healthy male subjects and evaluate its safety preliminarily in order to provide the scientific basis for a phase Ⅱ/Ⅲ clinical trial and clinical use of the drug.Methods Healthy male subjects were collected and received a single intravenous bolus injection of bivalirudin 0.75 mg/kg.Plasma concentrations of bivalirudin within 180 min after injection were determined by liquid chromatography-tandem mass spectrometric(LC-MS/MS) method for pharmacokinetic analysis.The activated clotting time were measured for pharmacodynamic analysis.At the same time,the vital signs and safety evaluation indexes were observed in all subjects before and after medication.Results Ten healthy male subjects were entered.Their age,height,weight,and body mass index were(29.5±3.4) years,(170.7±5.5) cm,(66±7) kg,and(22.2±1.7) kg/m2,respectively.The pharmacokinetic parameters were as follows: peak concentration(Cmax)(8347±1586) μg/L,peak time(Tmax) 5 min,elimination half-life(T1/2z)(41.6±9.0) min,area under the curve(AUC0-t)124.0(98.4-182.3) min·μg/L,area under the curve(AUC0-∞)(131.9±26.8) min·μg/L,mean retention time(MRT0-t)(25.6±3.1) min,volume of distribution(Vz)(354.8±103.9) ml/kg,clearance(CL)(5.9±1.1)ml/(min·kg).The pharmacodynamic parameters were as follows: basic effect(E0)(146±17) s,concentration for 50% of maximal effect(EC50)2225(799-42 008) μg/L,maximal effect(Emax)(4072±294) s.No changes in X-ray,cranial CT,12-lead ECG and laboratory examination(routine blood and urine tests,blood biochemical tests,immunological tests,5 tests of coagulation) were observed after the trail.No adverse drug reaction occurred during the trial.Conclusion Homemade bivalirudin seems to have the characteristics of rapid onset of action and shorter half-life and might be used as a safer anticoagulant in patients undergoing percutaneous coronary intervention.

OBJECTIVE To evaluate the pharmacokinetics of fasudil injection after single dose intravenous infusion in Chinese health volunteers.METHODS The plasma and urine samples of 12 healthy volunteers were collected after injecting 35 mg fasudil mesylate(FM) or 30 mg fasudil hydrochloride(FH).The concentrations of fasudil and hydroxyfasudil in plasma and urine were determined by a validated HPLC-MS/MS method.Pharmacokinetic parameters were calculated by software DAS2.1.1.RESULTS Fasudil concentration-time curves of test and reference formulations were discribed by the one compartment open model.The main pharmacokinetic parameters of fasudil were as follow: ρmax(200±46)and(188±52)μg·L-1,t1/2(0.398±0.130) and(0.335±0.087)h,AUC0-t(58.7±16.1) and(69.0±30.2)μg·h·L-1,respectively.The 24 h cumulative recovery in urine were(5.43±2.66)% and(5.29±2.10)% respectively,urinary excretion rates were above 40%.CONCLUSION The pharmacokinetic parameters of FM is similar to FH,and its clinical application can refer to FH(2-3 times per day,30 mg once,iv,30 min).

During the drilling process,it is very important to identify formation lithology in order to select bit types,quickly establish the lithology section,discover the oil and gas layers in time,and locate the coring layer exactly.Based on the mud logging data and combining with the logging data of the drilled wells,an artificial bee colony algorithm based on BP neural network is established for lithology identification.This model was verified in Qinghai oilfield.Compared with the geological explanation of logging data,the prediction result of the model is much better than ever before and the efficiency coefficient can reach as high as about 91.35%.

Objective To investigate the histopathologic changes in the rabbits' ear veins induced by different concentrations of sodium aescinate(SA). Methods Thirty-two rabbits were randomly divided into four groups (8 in each group) : the low-dose SA group, the moderate-dose SA group, the high-dose SA group and the control group. The first 3 groups were respectively infused with 1 mg/10 ml, 2 mg/10 ml and 4 mg/10 ml solutions of SA into one ear vein within 15 min 3 days. The control group was administrated with the same volume of normal saline. The ears of rabbit were observed every day for adverse reactions. After the last infusion, the rabbits were killed by an overdose of sodium pentobarbital. The histopathologic changes in the rabbits' ear veins were observed under light microscope. Results Compared with the control group, infusion of sodium aescine of different concentrations caused marked pathological damage on the part around the ear vein. The median (interquartile range) of the scores of the loss of venous endothelial cells, inflammatory cell infiltration and edema of the proximal regions in the moderate-dose SA group were 1.0(1.5),1.5(1.0),1.0(0.5) scores, the loss of venous endothelial cells and inflammatory cell infiltration of the distal regions in the moderate-dose SA group were 2.0(2.0) ,1.0(2.0) scores, the loss of venous endothelial cells, inflammatory cell infiltration and edema of the proximal and distal regions in the high-dose SA group were 2.0(1.0) ,2.0(0. 0) ,2. 0(1. 0) scores and 3.0(1.0) ,2. 0(2. 0) ,2. 0(2. 0) scores. Compared with the control group,the above indicators were statistically significant differences(P<0.05). The high-dose SA group(4 mg/10 ml) displayed the most severe phlebitis symptoms. There were no statistically significant differences in pathological damages between the proximal and distal regions in the high-dose SA group (P > 0. 05 ). Conclusions The phlebitic effect of SA on rabbits is related to dosage. Specifically, higher dosage of the drug can cause more severe phlebitis.

Urban Planning,as an independent branch separated from architecture,has its own unique research area and academic category. While in terms of the architecture design training,urban planning still stands an essential role.In teaching ideology,research targets, analysis methods,the urban planning education has its own characters.This article,taking the architecture major of China University of Mining &Technology,Beijing for example,points out the shortcomings of the courses of urban planning education,puts forward the process of "Survey—Analysis—Thinking—Design",and introduces the teaching methods and concept of urban planning programs.

OBJECTIVE:To investigate the pharmacokinetic characteristics of Azelnidipine tablets in Chinese healthy volunteers.METHODS:20 healthy volunteers(10 for male,10 for female)were randomly divided into two dosage groups and received oral dose of Azelnidipine tablets 8 or 16 mg,respectively.The blood concentration of azelnidipine was determined by LC-MS and the pharmacokinetic parameters were calculated using DAS2.1.1 software.RESULTS:Main pharmacokinetic parameters of azelnidipine in health tavinovdleu(nrat6et.ie6or2:s± 1af.29te.02r±3)th1μe.g 2.s0iLn;g-rl1ae;n ta1g/n2eβ(d o 2mf3 mu.0lot±itpiol6en.8:o)1rha.8l a5dn±ods(0e.24o59f..5 8N± mo9 gs.5ig)wnheir;feiAc aaUnsC tf 0od～li9lf6of(hewr4esn:4c.1tem±sa(x e12x9.i.6s6t±)edμ0 gi..n6) h4.h Ltra-on1ud(gahn2d.c8(o±n1c10e3.n9±)trah6t;7ioc.0mn)as(xμ o4g.f.1mh6.±uLlt-1ip1.;8le6 a)dcocμsugem.s uLalda--1 ministration(P=0.058).The pharmacokinetic parameters of azelnidipine in health volunteers after the single oral dose of 16 mg were 7faos6u)fnoμdllg.o.Twhhs.e:tdLmao(x-sa12.g.7eP± hoaf0r m.t6h)aech ot,rkicaimnla(xewti1ac0s.p6sa±arfae5m.a4e)ntdeμr gsn.ooL fs-e1sv,ientrg1e/l2 eβ(A dD2o5Rs.2e o ±wf 1ae3zree.8 l)nciohdn,ispCiisnLtee/nFo(t c8wcu0ir.t5hre± dth.5 oC0s.Oe4)NoLfC.LmhU-u1Sl,tIipOVlNe1/F:(doT7s0he6e,±mn5oe1t h1go)ednL d,ise rAs eUdniCfsfi0et～irv9e6en(h,c1ea3 cw2c±uasrate and simple,and it provides reference for clinical drug use.

OBJECTIVE To assess the effects of high-fat meal on the pharmacokinetic(PK) and pharmacodynamic(PD) properties and safety profile of aranidipine(AR) and its active metabolite,hydroxyl-aranidipine(AR-M1),in health Chinese subjects.METHODS One single-dose,open-label,randomized,crossover study of oral aranidipine enteric-coated capsule was conducted in healthy Chinese subjects.Twelve healthy nonsmoking subjects(6 males,6 females) aged from 18 to 45 years were orally administrated aranidipine enteric-coated capsule 10 mg in fasted state.After a washout period of 1 week,the subjects were orally administrated aranidipine enteric-coated capsule 10 mg after high-fat breakfast.Plasma samples were collected previous to the administration as well as at indicated time points after the administration.Concentrations of AR and AR-M1 in plasma were determined by HPLC-MS/MS.PK parameters(AUC0-t,AUC0-∞,ρmax,tmax,t1/2,Ke,CL/F,Vd/F,etc.) of AR and AR-M1 were calculated with DAS 2.1.1.Systolic and diastolic blood pressure(SBP and DBP) and heart rate(HR) were measured before and at indicated time points after the administration.Safety profile assessment was performed throughout the experiment.RESULTS There was significant increase in AUC0-t,AUC0-∞,and tmax for AR given after high-fat meal compared with those in fasted condition(P<0.05).For AR-M1,there was extremely significant increase in tmax(P<0.01) under high-fat meal condition and no significant difference in other parameters(P>0.05).There were no significant changes in BP and HR after the administration in a high-fat meal state compared with that in fasted state.Compared with baseline,there was significant decrease in DBP at 8 h after the administration in both fasted and high-fat meal state(P<0.05).CONCLUSION Oral administration of aranidipine enteric-coated capsule after high-fat meal results in slow absorption and significant increase in bioavailability of AR,as well as significant delay in the generation of AR-M1.There were no significant changes in BP and HR after the administration in either fasted or high-fat meal state.No serious AEs were observed during the experiment,showing the good safety profile of the agent.There is no need to adjust the dosage in clinic application,but light-food and administration in fasted state are recommended.

Objective To study the relationship between homocysteine (Hcy) and carotid atherosclerosis in the hypertensive patients.Methods Totally 300 patients with essential hypertension were enrolled in this study..According to the results of carotid artery ultrasonography,all patients were divide three groups.Homocysteine (Hcy),fasting blood glucose (FBG),triglyceride (TG),cholesterol(CHO),low density lipoprotein cholesterol (LDL),high density lipoprotein cholesterol (HDL),systolic blood pressure (SBP),diastolic blood pressure (DBP),age,sex,and smoking status were measured/recorded.Logistic multivariate regression analysis was performed to analyze the risk factors of carotid atherosclerosis.Results Hcy,SBP,DBP,age,and smoking status were significantly different among these three groups.Hcy,SBP,DBP,age,and current smoking were independently correlated with carotid atherosclerosis.Conclusion Hcy is one of the independent risk factors of carotid atherosclerosis in hypertensive patients

Objective A RP-HPLC method with fluorescence detector was established to determine telmisartan in human plasma. Methods Internal standard method quantifying telmisartan concentration in plasma was performed and valsartan was used as the internal standard. Plasma samples containing drug were extracted with benzene under acidic condition, followed by drying with nitrogen. The residual products were redissolved with mobile phase prior to analysis. Separation was performed on a reverse phase ZORBAX Eclipse XDB-C18 column(4.6×150 mm,5 μm), equipped with a pre-column of the same material(4.6×12.5 mm, 5 μm). The mobile phase contained methanol-acetonitrile-10 mmol/L potassium dihydrogen phosphate buffer, pH 3.2(5∶40∶55, v/v/v). The flow rate was set at 1.0 mL/min and the injection volume was 20 μL. The excitation and emission wavelengths were 250 nm and 375 nm, respectively. The column temperature was 25 ℃. Results No intrinsic substances interfered with analysis of telmisartan. The retention times were 8.8 min for telmisartan and 10.7 min for valsartan. The good linear relationship was obtained over the range(1~180)μg/L and the equations were determined by least squares linear regression analysis. The linear equation was A=0.2769R+0.03788. The linearity of the relationship between peak area ratio and amount ratio was demonstrated that the correlation coefficient was 0.9995. The limit quantification(LOQ) was set at 1 μg/L of telmisartan in human plasma. The average recovery rates were 97.53%, 104.6% and 105.1 % for plasma quality control(QC) samples at 2.0, 30, 70 μg/L, respectively. The RSDs of inter-and intra-day were all less than 7% for low, medium, high plasma QC samples. The intra and inter-assay precision and accuracy of the quality control and limit of quantification were satisfactory in all cases. Plasma samples were stable in the chromatographic rack for 24 h at room temperature, but we recommended storing processed plasma samples at 4 ℃ until the analysis. Conclusion The developed method was validated with respect to selectivity, linearity, accuracy, LOQ and stability. The experimental datum has proved that the above described method would provide accurate, rapid, simple and sensitive measurements of telmisartan in plasma. It is more suitable to determine telmisartan concentration in plasma and study the pharmacokinetics of telmisartan.