盐酸西替利嗪的药物动力学及其制剂的生物等效性

采用改进的高效液相色谱法 ,以盐酸羟嗪为内标 ,测定了 12名健康男性受试者口服盐酸西替利嗪胶囊和盐酸西替利嗪片后不同时刻血浆中西替利嗪的浓度 ,绘制了血药浓度 时间曲线 ,并求出两种制剂的主要药物动力学参数 :Cmax分别为 (90 5 7± 185 9)和 (777 1± 10 5 8)ng/mL ,Tmax分别为 (0 79± 0 2 6 )和 (0 90± 0 45 )h ,t1/ 2 分别为 (7 5 9± 1 2 9)和 (7 73± 1 46 )h ,AUC0→∞ 分别为 (6774 8± 10 5 9 1)和 (6 6 0 3 2± 12 5 7 6 )ng·h/mL .以AUC0→∞ 计算相对生物利用度 ,盐酸西替利嗪胶囊的相对生物利用度平均为 (10 4 0± 14 4) % .采用方差分析和双单侧t检验法进行生物等效性判断 ,结果表明 ,两种制剂生物利用度无显著性差异 (P >0 0 5 ) ,可认为两者在人体内生物作用等效     

甲壳胺对盐酸西替利嗪胶囊药代动力学和生物利用度的影响

目的测定甲壳胺(辅料)对盐酸西替利嗪胶囊(抗过敏药)的药代动力学和生物利用度的影响。方法18名健康志愿者随机交叉单剂量空腹口服盐酸西替利嗪市售片20mg和以甲壳胺为辅料的盐酸西替利嗪胶囊20mg后,用高效液相色谱法研究药物在体内的经时过程,并计算主要药代动力学参数。结果口服2种制剂20mg后,Cmax分别为1302.1、923.3ng·mL-1;t1/2分别为8.27、7.63h;tmax分别为0.82、1.21h;AUC0-t分别为(11.46±1.21)、(7.98±1.17)mg·h·mL-1;AUC0-∞分别为(12.45±1.37)、(8.24±1.32)mg.h·mL-1;其相对生物利用度为150.1%。结论甲壳胺可显著提高盐酸西替利嗪胶囊的生物利用度,明显改善药物的吸收。     

盐酸曲美他嗪胶囊的人体生物等效性

目的 评价国产盐酸曲美他嗪胶囊和进口盐酸曲美他嗪包衣片的人体生物等效性.方法 20名健康男性受试者按两制剂两周期的交叉试验设计单剂量口服20 mg的参比制剂和受试制剂后,采用LE-MS法测定血浆中盐酸曲美他嗪的浓度,使用DAS 1.0软件计算药动学参数并进行生物等效性统计分析.结果 参比制剂和受试制剂的ρmax分别为(55.9±9.2)和(56.4±12.2)μg·L-1;tmax分别为(2.5±0.8)和(2.7±0.9)h;AUC0→24h分别为(493.8±82.8)和(489.8±108.4)μg·h·L-1;AUC0→∞分别为(513.7±88.6)和(510.1±116.8)μg·h·L-1;t1/2分别为(4.8±0.4)和(4.7±0.4)h.双单侧t检验结果显示受试制剂的ρmax、AUC0→24h的90%置信区间分别为参比制剂相应参数的92.0%～108.4%和91.5%～105.3%,受试制剂的相对生物利用度为(99.6±16.5)%(以AUC0→24h计算).结论 国产盐酸曲美他啶胶囊与其进口包衣片具有生物等效性.     

盐酸丙哌维林散在健康人体内的生物等效性研究

目的 评价盐酸丙哌维林在健康人体内的相对生物利用度及生物等效性.方法 受试者随机、自身双交叉、单剂量口服受试制荆和参比制剂20 mg,采用液相-质谱(LC-MS)法测定血浆中药物浓度,药代动力学参数通过DAS软件处理获得.结果 两种制剂的峰浓度(Cmax)分别为(63.47±25.46)ng/mL和(61.51±22.31)ng/mL,达峰时间(Tmax)分别为(1.7±0.7)h和(1.7±0.7)h,半衰期(t1/2)分别为(12.68±4.11)h和(12.35±3.09)h,0-tn药时曲线下面积AUC0-tn为(827.62±370.02)ng/(mL·h)和(804.76±380.73)ng/(mL·h),0-∞药时曲线下面积AUC0-∞分别为(881.77±412.22)和(848.63±409.22)ng/(mL·h);受试制剂的相时生物利用度为(111.22±37.21)%.结论 石家庄市华新制药厂研制的盐酸丙哌维林散与其生产的盐酸丙哌维林片具有生物等效性.     

伊曲康唑分散片人体药动学及生物等效性研究

目的:研究伊曲康唑分散片和伊曲康唑胶囊在正常人体的药动学与生物等效性.方法:18名健康男性志愿受试者随机交叉口服0.2g单剂量伊曲康唑分散片受试制荆和伊曲康唑胶囊参比制剂后,采用高效液相色谱法测定伊曲康唑的血浆药物浓度,采用方差分析及t检验判定其生物等效性.结果:两种制剂均符合一级吸收开放性一室模型,伊曲康唑分散片和伊曲康唑胶囊主要药代动力学参数AUC0→72分别为(2 221.9±762.9)和(2 311.9±844.4)ng/(h·mL),AUC0→∞分别为(2 374.2±790.8)和(2 473.3±878.9)ng/(h·mL),Cmax分别为(179.8±56.8)和(174.1±64.1)ng/mL,Tmax分别为(3.6±1.0)和(4.1±1.3)h,t1/2分别为(16.5±4.2)和(17.5±3.1)h.伊曲康唑分散片的相对生物利用度为(97.8±14.0)%.结论:伊曲康唑分散片和伊曲康唑胶囊为生物等效制剂.     

普伐他汀钠片人体生物等效性研究

目的 研究普伐他汀钠片的人体相对生物利用度和生物等效性.方法 采用2阶段随机交叉设计,20例男性健康受试者分别单次口服两种普伐他汀钠片20 mg,以高效液相色谱-质谱联用(LC-MS/MS)法测定普伐他汀及其代谢物R-416的血药浓度.以普伐他汀及其代谢物R-416浓度之和计算药动学参数.结果 受试制剂与参比制剂的血药峰浓度(Cmax)分别为(129.9±54.4)ng/mL和(139.5±61.1)ng/mL,达峰时间(Tmax)分别为(1.1+0.5)h和(0.9±0.3)h,药时曲线下面积(AUC)0-1分别为(303.6±90.4)h-ng/mL和(306.5±114.0)h·ng/mL,AUC0→inf分别为(336.8±99.8)h·ng/mL和(334.1±118.8)h·ng/mL.受试制剂的平均相对生物利用度以AUC0→t计算为(99.0±25-2)%,以AUC0→inf计算为(100.8±24.6)%.结论主要药动学参数AUC-→t、AUC0→inf及Cmax的统计学分析结果 表明,两种制剂具有生物等效性.     

盐酸左西替利嗪口服液的人体相对生物利用度研究

目的:研究盐酸左西替利嗪口服液在正常人体内的药代动力学与相对生物利用度。方法:选择18名男性健康志愿者,采用反相高效液相色谱法,检测波长229nm,测定口服单剂量5mg盐酸左西替利嗪片或口服液后人体内的血药浓度,计算相应的药动学参数。结果:盐酸左西替利嗪片与口服液的Cmax分别为(230.42±35.67)ng/mL、(250.46±41.07)ng/mL,Tmax分别为(1.32±0.44)h和(0.90±0.33)h,AUC(0～T)分别为(3504.67±510.37)ng.h.mL-1和(3306.47±672.32)ng.h.mL-1,相对生物利用度为100.06%±13.99%。结论:盐酸左西替利嗪片与口服液具有生物等效性。     

盐酸曲美他嗪片的生物等效性研究

目的:研究盐酸曲美他嗪片的人体生物利用度和生物等效性。方法:22名男性健康受试者,随机双交叉口服剂量为20mg的受试制剂和参比制剂,采用LC-MS法测定血浆中盐酸曲美他嗪的浓度,使用DAS2.1.1软件对各药代动力学参数进行计算,同时对其生物等效性进行统计分析。结果:22名健康受试者服用20mg盐酸曲美他嗪片受试制剂和参比制剂的Cmax分别为(42.64±17.00)ng/ml和(41.32±19.66)ng/ml,Tmax分别为(2.2±1.5)h和(2.7±1.7)h,AUC0-t分别为(418.1±177.4)ng·h/ml和(397.8±147.1)ng·h/ml,AUC0-∞分别为(428.5±181.1)ng·h/ml和(407.9±150.5)ng·h/ml,t1/2分别为(5.9±1.6)h和(5.6±1.3)h。受试制剂中曲美他嗪Cmax的90%置信区间为参比制剂的100.1%～111.1%,AUC0-t的90%置信区间为参比制剂的97.0%～111.9%,AUC0-∞的90%置信区间为参比制剂的96.9%～111.9%。以AUC0-t计算,受试制剂中曲美他嗪的相对生物利用度为(105.9±18.6)%。结论:两制剂具有生物等效性。     

进口和国产盐酸特拉唑嗪片的人体生物等效性研究

目的：比较进口和国产盐酸特拉唑嗪片剂药动学及人体生物等效性。方法：24名健康男性受试者随机交叉口服盐酸特拉唑嗪受试制剂和参比制剂2 mg,血浆样品经直接沉淀后,采用液相色谱-串联质谱（LC-MS/MS）法测定特拉唑嗪浓度,计算药动学参数。对主要药动学参数进行统计学分析,评价两制剂的生物等效性。结果：盐酸特拉唑嗪受试制剂和参比制剂主要药动学参数分别为：t1/2（9.55±1.19）和（9.95±1.45）h,tmax为（1.20±0.88）和（1.28±1.28）h,cmax为（57.59±16.61）和（57.12±17.83）ng/mL,AUC0～48为（621.96±152.54）和（607.52±126.03）ng.h.mL^-1,AUC0～∞为（640.81±156.06）和（628.52±127.69）ng.h.mL-1。受试制剂的相对生物利用度为（102.10±9.91）%。结论：盐酸特拉唑嗪受试制剂和参比制剂具有生物等效性。     

奥美拉唑胶囊的人体药代动力学及生物等效性试验研究

目的建立测定奥美拉唑血药浓度的高效液相色谱法,并考察奥美拉唑胶囊人体药代动力学,比较两种制剂的生物等效性。方法采用双周期随机交叉试验设计,18例男性健康志愿者随机分为2组,分别单剂量交叉口服奥美拉唑胶囊(受试制剂)和奥美拉唑肠溶胶囊(参比制剂)40 mg,以反相高效液相色谱法测定给药后不同时间点的奥美拉唑血药浓度,采用DAS房室模型法和生物等效性计算程序进行统计分析。结果奥美拉唑胶囊(受试制剂)和奥美拉唑胶囊(参比制剂)血药浓度-时间曲线符合一室开放模型。主要药动学参数:t1/2分别为(1.76±0.79)h和(1.66±0.52)h,Tmax分别为(2.73±0.35)h和(2.61±0.4)h。Cmax分别为(1 271.09±351.72)ng/mL和(1 219.02±325.53)ng/mL,AUC0→∞分别为(2 941.85±807.18)ng/(h.mL)和(2 960.57±802.91)ng/(h.mL)。受试制剂对参比制剂的相对生物利用度为(99.63±12.04)%。结论受试制剂与对照制剂比较,其奥美拉唑的t1/2、Tmax、Cmax和AUC0→∞均无显著性差异,两种制剂具有生物等效性。     

Applications of derivative UV spectrophotometry for the determinations of cetirizine dihydrochloride in pharmaceutical preparations

A method for the determination of cetirizine dihydrochloride in pharmaceuticals by first-, second-, third- and fourth- order derivative spectrophotometry is described, using "peak-peak" (P-P), and "peak-zero" (P-0) measurements. The calibration curves are linear within the concentration range of 7.5-22.5 microg ml(-1) for cetirizine dihydrochloride. The procedure is simple, rapid and the results are reliable.     

Stability of cetirizine dihydrochloride in solid state

Influence of temperature and relative humidity on stability of cetirizine dihydrochloride in solid state was followed by HPLC method in this study.     

Determination of cetirizine in human plasma using high performance liquid chromatography coupled with tandem mass spectrometric detection: application to a bioequivalence study

A rapid, sensitive and selective HPLC-MS/ MS method was developed and validated for the quantification of cetirizine dihydrochloride (CAS 83881-51-0) in human plasma using mosapride citrate as internal standard (IS, CAS 112885-42-4). Following liquid-liquid extraction, the analytes were separated using a mobile phase consisting of methanol and aqueous ammonium acetate solution (10 mM) (60:40, v/v) on a reverse phase C18 column and analyzed by a triple-quadrupole mass spectrometer in the selected reaction monitoring (SRM) mode using the respective [M+H]+ ions, m/z 398 --> 201 for cetirizine and m/z 422 --> 198 for mosapride. The analysis time for each run was 8.0 min. The assay exhibited a linear dynamic range of 0.5-500 ng/ml for cetirizine dihydrochloride in human plasma. The lower limit of quantification (LLOQ) was 0.5 ng/ml with a relative standard deviation of less than 15% (all the concentration data in this study related to the salt (cetirizine dihydrochloride)). Acceptable precision and accuracy were obtained for concentrations over the standard curve range. It is the first time that the validated HPLC-MS/MS method has been successfully applied to a bioequivalence study in 20 healthy male Chinese volunteers.     

含氮化合物的构型与构象变化对核磁共振图谱的影响含氮化合物的构型与构象变化对核磁共振图谱的影响

目的寻找盐酸洛美利嗪等含氮化合物呈现特殊核磁图谱的内在原因。方法假设这些化合物存在构型和构象的变化导致核磁图谱的复杂化。用核磁方法证实这种假设的可信性。结果与结论盐酸洛美利嗪、盐酸西替利嗪两化合物的氮原子翻转形成两种椅式构象。在二甲亚砜溶液中其变换速度与核磁时标相近,无法测得确切的化学位移。所有谱线呈现不同程度的弥散,甚至坍塌、“消失”。加入少量水或升高测试温度降低了溶液的粘度,变换速度快于核磁时标,此时即可获得正常的图谱。芬氟拉明的氨基被樟脑酰胺化后限制了氮的3个键的翻转,不对称氮的存在可产生另一对非对映异构体。其碳谱显示所有谱线倍增的特殊现象可得到合理的解释。     

Effect of haemodialysis on the pharmacokinetics of cetirizine

Summary The pharmacokinetics of Cetirizine, a histamine H1-receptor antagonist, were investigated in five renal failure patients undergoing chronic haemodialysis therapy. The patients received one 10 mg cetirizine dihydrochloride capsule 3 h before haemodialysis.Concentrations of cetirizine in serum and dialysate were determined by HPLC. The maximum serum cetirizine concentration and the time to reach that maximum were 285 g·1^–1 and 2.0 h, respectively. The terminal disposition half-life of cetirizine in these patients was 19.3 h.The haemodialysis clearance of cetirizine was 14.0 ml · min^–1. Although this is approximately 33% of the apparent total body clearance of cetirizine in subjects with normal renal function, the fraction of the dose removed by dialysis was only 9.4%. Thus, since haemodialysis does not produce a clinically significantly alteration in cetirizine elimination, no supplemental dose should be necessary after dialysis.     

Development and validation of a dissolution test for a once-a-day combination tablet of immediate-release cetirizine dihydrochloride and extended-release pseudoephedrine hydrochloride

A dissolution test for a once daily combination tablet containing 10 mg of cetirizine dihydrochloride (cetirizine HCl) for immediate release and 240 mg of pseudoephedrine hydrochloride (pseudoephedrine HCl) for extended release was developed and validated according to current ICH and FDA guidelines. The cetirizine HCl is contained within an outer layer of the tablet while a semipermeable membrane of cellulose acetate and polyethylene glycol controls the rate at which pseudoephedrine HCl is released from the tablet core. The dissolution method, which uses USP apparatus 2 with paddles rotating at 50 rpm, 1000 ml of deaerated water as the dissolution medium, and reversed-phased HPLC for quantitation, was demonstrated to be robust, discriminating, and transferable. These test conditions were selected after it was demonstrated that the cetirizine HCl portion of the tablet rapidly dissolved in aqueous media over the physiologically relevant pH range of 1.1-7.5, and that the extended-release profile of pseudoephedrine HCl was independent of dissolution conditions (i.e., apparatus, pH, and agitation).     

左旋盐酸西替利嗪的合成工艺改进

目的研究左旋盐酸西替利嗪的合成工艺。方法以氯代苯和苯甲酰氯为起始原料。经傅克酰化、还原胺化得到左旋盐酸西替利嗪的关键中间体4-氯双苯胺（4），4再经拆分、成环、缩合制得左旋盐酸西替利嗪。结果与结论目标化合物的结构经红外光谱、元素分析确证，总收率为9．96％。该工艺操作简便，适用于工业化生产。     

Spectrophotometric and high performance liquid chromatographic determination of cetirizine dihydrochloride in pharmaceutical tablets

Derivative spectrophotometric, colorimetric and high performance liquid chromatographic methods, for the determination of the antihistaminic cetirizine dihydrochloride in tablet form were described. Spectrophotometrically, cetirizine was determined by the measurement of its first (¹D) and second (²D) derivative amplitudes at 239 (peak) and 243–233 nm (peak-to-trough), respectively. The aqueous solutions obeyed Beer's law in the concentration ranges of 1.2–10.0 and 0.8–10.0 μg ml⁻¹ for ¹D and ²D measurements, respectively. The colorimetric procedure was based on measuring the absorbency of the coloured chromogen resulted from the reaction between cetirizine sodium salt in polar solvent (DMF) and chloranil at 556 nm. The relation with concentrations was linear over 120–250 μg ml⁻¹. Optimization of the reaction conditions was studied. At the same time, investigation of the complex formed was made with respect to its composition and the associated constant. A simple liquid chromatographic assay has been developed for the determination of cetirizine dihydrochloride in the presence of one of its synthesis precursor (hydroxyzine hydrochloride). A Bondapak-C₁₈ column was used with a mobile phase consisting of acetonitrile/0.01 M ammonium dihydrogen phosphate (32:68, v/v) containing 0.1% w/v tetrabutyl ammonium hydrogen sulphate adjusted to pH 3 with phosphoric acid at a flow rate of 2 ml min⁻¹. With salicylic acid as internal standard, quantitation was achieved with UV detection at 230 nm based on the peak height ratios. Beer's law was obeyed in a concentration range of 3–35 μg ml⁻¹ and the regression line equation was derived with a correlation coefficient of 0.9999. The validity of the methods was further confirmed using the standard addition method. The proposed procedures were successfully applied to the determination of cetirizine in bulk and tablet form, with high percentage of recovery, good accuracy and precision.     

盐酸西替利嗪滴剂联合孟鲁司特钠咀嚼片治疗儿童咳嗽变异性哮喘的临床研究

目的 观察盐酸西替利嗪滴剂联合孟鲁司特钠咀嚼片治疗儿童咳嗽变异性哮喘(CVA)的临床疗效及安全性.方法 将110例CVA患儿随机分为对照组和试验组,每组55例.对照组给予孟鲁司特钠咀嚼片,3～6岁每次4 mg,qd,6～12岁每次5 mg,qd,每晚顿服;试验组在对照组治疗的基础上,给予盐酸西替利嗪滴剂,3～6岁每次0...