口服奥硝唑唾液浓度的测定及药动学研究

目的测定健康志愿者口服奥硝唑胶囊唾液药物浓度并观察其药动学特征。方法利用HPLC法测定奥硝唑的唾液药物浓度,根据唾液药物浓度求算12名健康志愿者单剂量口服奥硝唑胶囊的药动学参数。结果药动学参数表明,奥硝唑人体内过程符合一室模型,Cmax、T1/2(Ke)、AUC0-∞分别为(18.28±2.80)mg/L、(15.74±1.94)h、(424.74±50.83)mg.h-1.L-1。结论实验证明,健康志愿者口服奥硝唑胶囊唾液药物浓度较高,且维持时间较长。     

健康人口服奥硝唑片的药代动力学研究

目的:研究健康人口服奥硝唑片的药代动力学特征.方法:12名健康志愿者单剂量口服奥硝唑片1 g,分别在服药后0 、0.5、1、1.5、2、3、4、6、8、10、12、24、48、72 h时取静脉血3 mL,分离血浆,采用HPLC测定奥硝唑的血药浓度,以3p97程序软件计算药代动力学参数.结果:药动学参数表明,奥硝唑人体内过程符合一室模型,Cmax,T1/2(Ke),Tpeak,AUC0-∞分别为(20.55 ±3.02)mg/L,(15.61 ±1.87)h,(0.76 ±1.18)h,(474.07 ±63.21)mg·h/L.结论:奥硝唑口服吸收快,消除半衰期长.     

奥硝唑血药浓度的高效液相色谱法测定及其国产和进口片剂的药动学和生物等效性研究

目的建立血浆中奥硝唑浓度的反相高效液相色谱分析方法,并用此法研究了国产和进口奥硝唑片剂在健康人体内的药动学及生物等效性.方法用甲醇/异丙醇(50/50)提取样本,采用Kromasil C18色谱柱,以甲醇:0.4%HAc(50∶50)为流动相,流速0.8mL·min-1,紫外检测波长316nm.18名健康男性志愿者随机交叉口服国产及进口奥硝唑片1.5g,测定其药动学参数,评价两种制剂的生物等效性.结果奥硝唑在2.0～20.0μg·mL-1范围内呈线性,r=0.9997,最低检测限0.2μg·mL-1.低、中、高浓度(2.0,10.0,20.0μg·mL-1)的方法回收率分别为100.36%,98.21%和97.42%,日间及日内RSD分别＜6%和＜7%.药动学研究表明,口服奥硝唑国产与进口制剂的药-时曲线符合有滞后时间的二室模型.其主要药动学参数如下:t1/2(β) 分别为(16.29±2.20)h 和(15.85±2.26)h ;Tmax 分别为(1.67±0.49)h 和(1.75±0.48)h; Cmax 分别为(22.03±3.53)mg·L-1 和(22.58±5.94)mg·L-1 ;AUC0～72 分别为(444.56±55.87)mg·h·L-1 和(433.31±58.52)mg·h·L-1 ;AUC0～∞分别为(462.95±55.35)mg·h·L-1 和(451.67±57.97)mg·h·L-1 .两种制剂主要药动学参数均无显著性差异(P＞0.05).国产奥硝唑片的相对生物利用度为(102.91±8.93)%.结论本法准确可靠,操作简便,适用于临床药动学研究及常规血药浓度监测.统计学检验结果提示,国产和进口奥硝唑片具有生物等效性.     

硫辛酸片在中国健康人体内的药动学研究

目的:研究硫辛酸片在中国健康人体内的药动学。方法:24名健康志愿者单剂量口服硫辛酸片200 mg,用HPLC-MS法测定健康受试者的血药浓度,并计算药动学参数。结果:主要的药动学参数如下:t1/2=(24.13±9.73)min,tmax(实测值)=(15.95±5.15)min,cmax=(1.54±0.29)μg/mL,k=(0.032 6±0.010 8)1/min,AUC0～t=(58.21±15.08)μg.min.mL-1,Vc/F=(126.65±56.67)L,CLs/F=(3.67±1.00)L/min,MRT0～t=(38.22±15.63)min。结论:中国健康志愿者口服硫辛酸片后的体内过程符合一级消除过程,本研究结果可以指导临床合理用药。     

塞克硝唑胶囊在健康人体内的生物等效性

目的研究塞克硝唑胶囊与片剂的药动学特征,并评价其生物等效性。方法随机交叉试验设计,20名健康志愿者单剂量口服塞克硝唑胶囊和塞克硝唑片剂1.5 g后,在规定时间取血,用HPLC法测定血药浓度,进行数据处理,计算2种制剂的主要药动学参数,进行人体生物利用度比较。结果受试制剂和参比制剂药动学参数分别为:tmax(2.00±0.00)、(2.15±0.37)h;ρmax(38.89±4.18)(、38.77±3.20)mg.L-1;ACU0→∞(1 320.25±287.29)(、1 292.40±234.39)mg.h.L-1;ACU0→96h(1 239.05±260.99)(、1 232.12±217.63)mg.h.L-1;t1/2(22.64±3.58)、(20.70±2.83)h;药动学参数差异无统计学意义。相对生物利用度(F)101.47%。结论塞克硝唑2种制剂在健康人体内具有生物等效性。     

盐酸曲马朵在健康中国志愿者体内的药动学差异

目的:考察健康中国志愿者单剂量口服盐酸曲马朵片后体内药动学的差异。方法:12例健康中国志愿者单剂量口服75mg盐酸曲马朵片后,用液相色谱-荧光法测定血浆药物浓度经时过程,DAS2.0程序计算主要药动学参数。结果:血浆盐酸曲马朵测定的线性范围为2.0～500μg.L-1,定量下限为2.0μg.L-1。测得的主要药动学参数Cmax,Tmax,t1/2,AUC(0-τ),AUC(0-∞),MRT(0-τ),MRT(0-∞),CL/F和V/F分别为(336.17±69.93)μg.L-1,(2.4±0.9)h,(7.27±3.01)h,(3231.44±1319.4)h.μg.L-1,(3820.57±2118.02)h.μg.L-1,(7.80±1.31)h,(10.97±4.40)h,(24.49±10.95)L.h-1和(222.10±50.83)L。结论:盐酸曲马朵在健康中国志愿者体内存在明显的代谢类型差异,临床需加强个体用药监测。     

三种左奥硝唑制剂在健康人体的生物利用度与生物等效性分析

目的比较3种国产左奥硝唑制剂在健康人体内的药代动力学,并评价3种制剂的生物等效性。方法 24名健康男性志愿者三交叉单剂量口服受试制剂左奥硝唑分散片、胶囊和参比制剂左奥硝唑片500mg后,用HPLC-UV法测定血药浓度,用DAS Ver 2.1计算其药代动力学参数并评价三者的生物等效性。结果受试制剂左奥硝唑分散片、胶囊和参比制剂左奥硝唑片的主要药代动力学参数:Cmax分别为(10.6±3.5)、(10.4±3.7)和(11.1±3.3)mg.L-1t;max分别为(0.76±0.70)、(1.35±0.80)和(0.92±0.84)ht;1/2分别为(13.2±1.4)、(12.9±1.7)和(12.3±1.9)h;AUC0→48分别为(140.7 31.3)、(149.5±28.5)和(143.2±37.2)mg.L-1.h;AUC0→∞分别为(152.6±33.4)、(162.0±31.8)和(153.7±30.1)mg.L-1.h。以AUC0→48、AUC0→∞作为评价依据,受试制剂对参比制剂的相对生物利用度F分别为(98.3±12.0)%、(99.512.1)%和(104.9±9.5)%、(106.0±10.5)%。结论左奥硝唑分散片、胶囊和参比制剂左奥硝唑片三种制剂生物等效。     

替硝唑结肠定位肠溶片的人体药动学研究

目的:研究替硝唑结肠定位肠溶片在健康受试者中的药动学特征.方法:对8例健康男性受试者接受单次口服2 000mg替硝唑结肠定位肠溶片后的药动学进行了研究.采用HPLC法测定血浆中药物浓度.结果:经3P87/3P97药动学计算程序处理拟合,数据符合口服给药一室开放模型,其药动学参数分别为:Tmax=(12.5±1.8)h,Cmax=(29.8±8.2)mg·L-1,AUC0～t=(1050.1±92.2)mg·h·L-1.结论:本试验提供了替硝唑结肠定位肠溶片的药动学参数,为临床应用提供了依据.     

国产替米沙坦胶囊在健康人体内的药动学

目的:研究国产替米沙坦胶囊在健康人体内的药动学。方法:10名健康志愿者单剂量口服120mg替米沙坦胶囊,采用高效液相色谱法测定血浆中替米沙坦浓度,并用3P97软件统计处理。结果:替米沙坦胶囊药-时曲线符合二室模型,其Cmax,tmax,t1/2,AUC0-84,AUC0-∞分别为(821.6±271.0)μg.L-1,(0.68±0.17)h,(24.6±2.5)h,(2 132±1 171)μg.L-1.h,(2 208±1 183)μg.L-1.h。结论:替米沙坦胶囊在人体内药动学过程符合二室开放模型,本试验可为临床用药提供药动学参数。     

口服大剂量维生素C的人体药动学

目的研究口服大剂量维生素C在健康人体内的药动学。方法10名健康志愿者单、多次口服1 g维生素C,采用HPLC法测定血浆中维生素C浓度,计算药动学参数。结果单次口服1 g维生素C,主要药动学参数t1/2为(12.1±2.71)h;ρmax为(22.0±3.18)mg.L-1;tmax为(2.0±0.4)h;AUC0→36 h为(223.9±35.7)mg.h.L-1;AUC0→∞为(254.3±53.3)mg.h.L-1。多次口服维生素C,主要药动学参数ρmax为(26.6±3.50)mg.L-1;tmax为(1.8±0.4)h;ρmin为(8.25±0.90)mg.L-1;ρav为(12.8±0.92)mg.L-1;AUCss为(299.2±23.3)mg.h.L-1;DF为(1.46±0.28)。结论每日口服1 g维生素C,能够达到临床治疗目的。     

苯丙哌林在健康人体内的对映体选择性药物动力学研究

目的　研究苯丙哌林在健康人体内的对映体选择性动力学过程。方法　以非手性HPLC法测定不同时刻血浆样品中苯丙哌林的浓度,再用手性HPLC法测定两对映体的浓度比值,计算得到血浆中(R)-和(S)-苯丙哌林的浓度。结果　6名受试者血浆中S体浓度始终高于R体,S体的AUC_0-t和C_max的均值分别为R体的2.12倍和2.18倍,但二者的T_1/2无显著性差异。服药后0.5 h血浆中S/R对映体浓度比值高达3.8,此后迅速下降,2 h后约为2.2,基本保持恒定到24 h。结论　口服(±)-苯丙哌林后, 两对映体在人体内的药物动力学过程具有显著的立体选择性。     

HPLC-MS/MS法测定人血浆中右旋雷贝拉唑和左旋雷贝拉唑浓度及其人体药动学研究

目的:利用手性色谱柱建立高效液相色谱-串联质谱(HPLC-MS/MS)法同时测定人血浆中右旋雷贝拉哇(dexrabeprazole,DLBLZ)和左旋雷贝拉哇(levrabeprazole,LLBLZ)的浓度,并用于注射用右旋雷贝拉唑钠的人体药动学研究.方法:采用AB Sciex API4000液质联用仪,ESI离子源...     

双氯芬酸钠缓释片在健康人体的药代动力学和生物等效性

目的:评价双氯芬酸钠缓释片受试制剂和参比制剂在健康人体的药代动力学和生物等效性。方法:24例健康男性志愿者分别行单剂量和多剂量交叉口服双氯芬酸钠缓释片受试与参比制剂,用高效液相色谱-串联质谱法测定血浆中双氯芬酸钠的血药浓度,计算药代动力学参数及相对生物利用度。结果:单剂量口服受试制剂和参比制剂的主要药动学参数如下:Cmax分别为(568.38±271.26)和(458.64±173.96)ng.mL-1,Tmax分别为5(0.5,12)和1.5(0.5,7)h,AUC0～24 h分别为(2 557.72±659.43)和(2 364.14±698.08)ng.h.mL-1,AUC0～∞分别为(2 655.25±635.48)和(2 843.62±808.61)ng.h.mL-1,MRT分别为(6.3±1.8)和(7.0±1.7)h;多剂量口服受试制剂和参比制剂的主要药代动力学参数为:T(ss,max)分别为5(1,7)和4(0.5,8)h,C(ss,max)分别为(520.58±245.89)和(522.98±234.36)ng.mL-1,C(ss,min)分别为(24.96±20.79)和(22.68±17...     

Evaluation of the pharmacokinetics of two recombinant human erythropoietin preparations: epoetin zeta and epoetin alfa. 1st Communication: A monocentric, open, randomized, single dose, two-period crossover trial in healthy volunteers

The pharmacokinetic properties of a new recombinant erythropoietin preparation (epoetin zeta, CAS 604802-70-2) compared to a reference product (epoetin alfa, CAS 113427-24-0) were analyzed after a single intravenous bolus injection of 10,000 IU in a two-period crossover design in 24 healthy volunteers. Peripheral venous blood samples were obtained pre-dose, and 0:05, 0:20, 0:40, 1:00, 1:20, 1:40, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 36:00, 48:00, and 72:00 hours post dosing. Samples of 24 volunteers were analyzed by means of a specific immunoassay (ELISA). Three volunteers were excluded from statistical analysis due to a paravasal injection in one of both study periods with resulting low plasma levels of epoetin. Comparison of both preparations showed nearly identical pharmacokinetic properties after intravenous administration. The usual bioequivalence limits were fulfilled for all relevant pharmacokinetic parameters.     

Aliskiren exhibits similar pharmacokinetics in healthy volunteers and patients with type 2 diabetes mellitus

BACKGROUND: The renin system is an attractive target for antihypertensive therapy in patients with diabetes mellitus. However, diabetes is associated with changes in gastrointestinal, renal and hepatic function that may affect the absorption and disposition of oral drugs. This study compared the pharmacokinetics and pharmacodynamics of the orally active direct renin inhibitor, aliskiren, in healthy volunteers and patients with type 2 diabetes. METHODS: This was an open-label study conducted in 30 patients with type 2 diabetes and 30 healthy volunteers matched for age, bodyweight and race. Following a 10-hour fast, all participants received a single oral dose of aliskiren 300mg. Blood samples were taken at frequent intervals for 96 hours post-dose for determination of plasma concentrations of aliskiren (using a high-performance liquid chromatography-tandem mass spectroscopy method). Plasma renin activity (PRA) and renin concentration (RC) were also measured for 24 hours after dosing. RESULTS: Aliskiren exhibited similar pharmacokinetics in patients with type 2 diabetes and healthy volunteers. Exposure to aliskiren was slightly higher in patients with type 2 diabetes compared with healthy volunteers (mean area under the plasma concentration-time curve from 0 to 24 hours 1859 vs 1642 ng . h/mL; maximum observed plasma drug concentration 394 vs 348 ng/mL), while apparent clearance corrected for bioavailability was slightly lower (205 vs 234 L/h) and elimination half-life slightly longer (44 vs 39.9 hours), but there were no statistically significant differences for any pharmacokinetic parameters. There was no significant correlation between glycaemic control (% glycosylated haemoglobin) and any of the measured pharmacokinetic parameters in patients with type 2 diabetes. Aliskiren caused sustained suppression of PRA for at least 24 hours after dosing despite increasing RC; there were no major differences in the pharmacodynamic effects of aliskiren between patients with type 2 diabetes and healthy volunteers. Aliskiren was well tolerated in both patient groups, with no clinically significant changes in laboratory values and a low risk of adverse events. CONCLUSION: Aliskiren showed a similar pharmacokinetic profile in healthy volunteers and patients with type 2 diabetes, and administration of a single oral 300 mg dose of aliskiren was well tolerated by both patients and healthy volunteers. The pharmacodynamic effects of aliskiren were also similar in healthy volunteers and diabetic patients, with sustained inhibition of renin system activity observed for at least 24 hours after dosing.     

兰索拉唑肠溶胶囊在健康人体的生物等效性

目的评价2种国产兰索拉唑肠溶胶囊制剂(抗溃疡药)的生物等效性。方法 24例健康成年男性受试者随机分组,按照自身对照的方法单次口服兰索拉唑肠溶胶囊30 mg,用LC-MS/MS测定兰索拉唑和其代谢物5-羟基兰索拉唑、兰索拉唑砜的浓度,用非房室模型方法计算主要药代动力学参数。结果参比制剂和试验制剂的主要药代动力学参数如下。兰索拉唑:t1/2分别为(2.10±1.58),(2.18±1.85)h;tmax分别为(2.20±1.10),(2.00±1.01)h;Cmax分别为(1160.8±550.3),(1232.3±628.1)ng.mL-1;AUC0-t分别为(4963.7±4233.4),(4947.0±4669.3)ng.mL-1.h;AUC0-∞分别为(5027.4±4256.9),(5036.0±4751.2)ng.mL-1.h。5-羟基兰索拉唑:t1/2分别为(1.95±1.20),(1.75±1.00)h,tmax分别为(2.10±1.20),(1.80±1.00)h,Cmax分别为(106.2±61.2),(114.5±61.0)ng.mL-1,AUC0-t分别为(279.1±124.2),(27...     

盐酸多沙普仑在中国汉族健康人体内的药动学

目的：研究盐酸多沙普仑注射液在汉族健康志愿者体内的药代动力学。方法：10名健康志愿者,男女各半,单次静脉滴注盐酸多沙普仑注射液50mg,定时采血,用反相高效液相色谱法测定血药浓度,DAS软件程序计算药动学参数。结果：多沙普仑的体内过程符合二室模型,主要药代动力学参数为Cma（x1.55±0.52）μg·mL^-1,T1/（23.87±2.17）h,Vd/F（1.35±0.96）L·kg^-1,AUC0（-t3.51±1.26）mg·h·L^-1,AUC0-∞（4.06±1.44）mg·h·L^-1。结论：多沙普仑的药动学参数与文献报道基本一致,可作为不同民族人群药动学研究的基础。     

多潘立酮片人体生物等效性研究

目的用高效液相色谱-质谱联用法(LC-MS/MS)测定受试者口服多潘立酮制剂后的血药浓度,估算受试制剂和参比制剂的药代动力学参数,评价2种制剂的生物等效性和相对生物利用度。方法采用随机二交叉设计试验,24例男性健康志愿受试者,单剂量口服受试制剂和参比制剂多潘立酮片。以LC-MS/MS测定血浆中多潘立酮的浓度。采用BAPP3.0软件处理计算主要药动学参数。结果受试制剂和参比制剂血浆中多潘立酮的半衰期(t1/2)分别为(10.2±1.9)和(10.2±2.2)h;达峰浓度(Cmax)分别为(26±11)和(25±12)μg/L,达峰时间(tmax)分别为(0.7±0.5)和(0.6±0.3)h;药-时曲线下面积(AUC0～36h)分别为(75±24)和(70±27)μg·h-1·L-1;AUC0-∞分别为(80±26)和(74±28)μg·h-1·L-1;人体相对生物利用度为(114±30)%。结论 2种制剂在健康人体内具有生物等效性。     

Enantioselective pharmacokinetics of Carvedilol in human volunteers

Carvedilol is administered as a racemic mixture of the R(+)- and S(-)-enantiomers, although they exhibit different pharmacological effects. To investigate the stereoselective pharmacokinetics, the enantiomeric separation of carvedilol in human plasma was undertaken using capillary electrophoresis (CE). Resolution of the enantiomers was achieved using 2-hydoxypropyl-beta-cyclodextrin as the chiral selector. Phosphate buffer (50 mM, pH 4.0) containing 10 mM of 2-hydoxypropropyl-beta-cyclodextrin was used as electrolytic buffer. Achiral separation was carried out with the same electrolytic buffer without chiral selector. Following a single oral administration of 25-mg carvedilol to 11 healthy, male volunteers, stereoselective pharmacokinetic analysis was undertaken. The maximum plasma concentrations (Cmax) were 48.9 and 21.6 ng/mL for (R)-carvedilol and (S)-carvedilol, respectively, determined by the chiral method. The profiles of the plasma concentration of (RS)-carvedilol showed Cmax of 71.5, 72.2, and 73.5 ng/mL, as determined by the CE, HPLC/FD methods and calculations from the data of the chiral method, respectively.