感冒一小时胶囊中黄芩苷在正常与发热大鼠体内动力学特点的比较

目的 :探讨感冒一小时胶囊中黄芩苷在正常和发热大鼠体内的代谢动力学。方法 :采用高效液相技术分别测定正常大鼠和干酵母致发热大鼠血浆中黄芩苷的含量 ,使用 3P87软件处理黄芩苷的时量数据 ,计算各药代动力学参数。结果 :在正常和发热大鼠体内 ,黄芩苷的达峰时间分别为 9.46± 1.69h和 7.2 0± 2 .74h( p =0 .12 ) ) ,峰值血药浓度分别为 1.44± 0 .3 9μg/ml和 1.0 9± 0 .44 μg/ml( p =0 .2 1) ,t1/ 2 (ke)分别长达 10 .89± 5 .87h和 16.60± 2 0 .88h ,t1/ 2 (ka)分别为 3 .85± 0 .94和 2 .3 5± 1.48(p =0 .0 9) ,CL/F值分别为 2 2 .12± 5 .3 7(mg/kg) /h( μg/ml)和 3 8.3 8± 2 2 .99(mg/kg) /h/( μg/ml) ( p =0 .16) ,AUC(O T)值分别为 2 .68± 5 .81( μg/ml) h和 16.12± 4.91( μg/ml) h(P <0 .0 5 )。结论 :发热明显降低黄芩苷在体内的AUC(O T) ,有加快黄芩苷吸收和消除的趋势。     

芹菜素壳聚糖微球在大鼠体内药物动力学研究

目的建立大鼠血浆中芹菜素含量测定的HPLC法,考察芹菜素壳聚糖微球在大鼠体内药动学特点。方法采用HPLC法测定芹菜素壳聚糖微球和芹菜素原料药在大鼠体内的血药浓度,计算药动学参数。结果芹菜素壳聚糖微球和芹菜素原料药的药动学参数t(peak)分别为2.67、1.95h,t1/2(ke)分别为3.12、2.64h,C(max)分别为1.60、1.86μg/ml,AUC分别为13.04、11.81μg/ml·h,CL分别为3.07、6.77μg·h/kg。结论芹菜素壳聚糖微球延长了芹菜素在大鼠体内的滞留时间,提高了芹菜素的治疗效果。     

注射用双黄连中连翘苷的药代动力学研究

目的:探讨注射用双黄连中连翘苷在大鼠体内的血药浓度及药代动力学。方法:SD系大鼠尾静脉注射双黄连后,于不同时间点采血,采用反相高效液相色谱法测定大鼠体内连翘苷的血药浓度,应用DAS 2.0软件计算药代动力学参数。结果:连翘苷在大鼠体内主要药代动力学参数为:t1/2(α)(0.44±0.06)h、t1/2(β)(2.77±0.36)h、V1(0.09±0.01)L/kg、CL(0.09±0.007)L/(h.kg)、AUC0～t(5.56±0.47)mg.h/L、AUC0～∞(6.44±0.53)mg.h/L。结论:连翘苷在大鼠体内符合二室开放模型,其特点为分布快、消除缓慢。     

京尼平苷在大鼠体内药代动力学性别差异研究

目的:建立大鼠血浆中京尼平苷和京尼平快速液相色谱-串联质谱(LC-MS/MS)检测方法,考察毒性剂量下,性别差异对京尼平苷在大鼠体内的药代动力学特征的影响。方法:将大鼠分为雌雄两组,分别灌胃给与700 mg/kg的京尼平苷水溶液,收集各时间点的大鼠血浆,采用LC-MS/MS法测定血浆京尼平苷和京尼平浓度,通过DAS 2.1.1软件计算主要药代动力学参数。结果:大鼠灌胃京尼平苷后,体内京尼平苷主要的药代动力学参数为:雄性组AUC(0-t)为(17860±6886)μg·h/L,Cmax为(3059±1499)ng/ml,t1/2为(7.4±3.4)h;雌性组AUC(0-t)为(17197±7576)μg·h/L,Cmax为(3904±1062)ng/ml,t1/2为(5.3±2.9)h。结论:灌胃700mg/kg京尼平苷后,京尼平苷药动学特征不具性别差异,而京尼平的药动学特征可能存在性别差异。     

蛇床子素β-环糊精包合物分散片的制备及大鼠体内药动学研究

目的 制备蛇床子素β-环糊精包合物以提高蛇床子素的水溶性,并考察体外释药特性及大鼠体内的药动学行为.方法 采用逆向混合搅拌法制备蛇床子素β-环糊精包合物,以崩解时限、硬度及溶出度为综合指标L9(34)正交实验,高效液相色谱法测定大鼠体内的血药浓度.结果 最终确定优选处方的辅料比例为10％微晶纤维素(MCC),6％低取代羟丙基纤维素(L-HPC)和12％交联聚维酮(PVPP);所制备的包合物分散片的崩解时间(52.7±2.4)s,硬度(5.13±0.47) kg,1h内的累积溶出度(93.1±1.2)％;大鼠体内原料药组的Tmax为2.65 h,Cmax为2.87 μg/mL,AUC0-24为21.32 μg·h/mL,包合物分散片组的Tmax为2.14 h,Cmax为36.64 μg/mL,AUC0-24为272.41μg·h/mL,经配对t检验,Tmax、Cmax、AUC0-24差异均有显著性(P＜0.05).结论 蛇床子素包合物分散片具有溶散快,分散均匀,有效成分溶出速率快的特性,并能提高其大鼠体内生物利用度.     

红花黄色素在急性血瘀大鼠体内的药代动力学研究

目的考察红花黄色素(saffloryellow,SY)在急性血瘀大鼠体内的药代动力学特征.方法通过皮下注射肾上腺素(0.07ml/kg)和冰水刺激造成大鼠急性血瘀模型后,将正常组和模型组分别尾静脉注射红花黄色素注射液(37.08mg/kg),并测定大鼠在5、10、30、60、120、180、300和480nin血清样品中药物浓度.结果血瘀大鼠的血药浓度-时间曲线符合二室开放模型,曲线下的面积(AUC)为49633μg@min/ml,分布半衰期(t1/2a)为1.43min,消除半衰期(t1/2β)为95.65min;而正常大鼠为一室模型,曲线下的面积(AUC)为42267μg@min/ml,半衰期(t1/2)为66.27min.结论红花黄色素在急性血瘀大鼠体内代谢明显慢于正常大鼠体内的代谢.     

安息香在大鼠体内的药代动力学研究

目的 建立安息香主要成分苯甲酸在大鼠体内的RP-HPLC测定方法,研究安息香在大鼠体内的药代动力学规律.方法 Agilent TC-C18色谱柱(250 mm× 4.6 mm,5μm);流动相为甲醇-水-磷酸(50∶50∶0.05,V/V);流速为1.0ml·min-1;检测波长为228 nm;柱温:25℃.结果 主要药代动力学参数为:雌性Cmax=(0.055 8±0.050 8)mg·ml-1,tmax =(1 ±0)h,t1/2=(0.168±0.084 5)h,AUC(0-∞)=(0.076 3±0.076 7)h·mg-1·ml-1;雄性Cmax=(0.077 4±0.0369) mg·ml-1,tmax=(1±0)h,t1/2=(0.533±0.417 4)h,AUC(0-∞)=(0.115 4 ±0.058 1)h·mg-1·ml-1.结论 所建立的RP-HPLC方法操作简便、准确灵敏、重复性好,可用于安息香在大鼠体内药代动力学研究.     

蛇床子素固体分散体分散片的处方优化及其体内外质量评价

目的:优化蛇床子素固体分散片的处方并考察其体内外释药特性。方法:以崩解时限、硬度的综合评分为指标,通过正交试验优选蛇床子素固体分散片的处方。采用RP-HPLC比较蛇床子素固体分散片和原料药体内外释药特性的差异。结果:最佳处方为蛇床子素固体分散体43.5%,微晶纤维素40%,交联聚维酮12%,低取代羟丙基纤维素4%,微粉硅胶0.5%;崩解时间(80.5±3.8)s,硬度(4.4±0.4)kg,分散均匀性好、混悬性好。分散片体外释药参数T50(药物溶出50%时间)和Td(药物溶出63.2%时间)分别为0.013,1.37 min,均明显优于原料药。固体分散片的达峰时间(tmax)1.00 h,达峰浓度(Cmax)37.42 mg·L-1,药时曲线下面积(AUC0~t)43.04 mg·L-1·h。结论:蛇床子素固体分散片具有分散均匀、有效成分溶出速率快的特性,能显著提高药物在大鼠体内的生物利用度。     

红花提取物在急性血瘀大鼠体内的药代动力学研究

目的:考察红花提取物在急性血瘀大鼠体内的药代动力学特征。方法:通过皮下注射肾上腺素(0.07mL/kg)和冰水刺激造战大鼠急性血瘀模型,将正常组和模型组分别灌胃给予红花提取物5.62g/kg(含HSYA 100 mg),并分别测定大鼠在不同时间点下血浆样品中羟基红花黄色素A(HSY)A的药物浓度。结果:血瘀大鼠的血药浓度-时间曲线符合二室开放模型,AUC为19.17±1.24mg/L.h-1,t1/2β为1.67±0.76 h,t1/2α为0.66±0.12h,Cmax为8.05±0.57mg/L;而正常大鼠的AUC为7.32±0.44mg/L.h-1,t1/2β为1.21±0.36h,t1/2α为0.25±0.08 h,Cmax为4.89±0.61mg/L。结论:红花提取物在急性血瘀大鼠体内吸收和代谢均明显慢于正常机体内,说明中医的证可以改变药物的代谢过程。     

川芎挥发油中藁本内酯在大鼠体内的药动学研究

目的 测定川芎挥发油中藁本内酯在大鼠体内的药动学.方法 采用RP-HPLC法,以蛇床子素为内标物测定大鼠口服川芎挥发油的β-环糊精包合物后藁本内酯的血药浓度,使用3P97药动学软件计算其药动学参数.结果 藁本内酯在大鼠体内符合二室模型,主要的药动学参数:t_(1/2)(α)为(1.429±1.161)h,t_(1/2)(β)为(6.877±2.275)h,t(peak)为(3.401±1.951)h,AUC为(70.87±25.92)μg/mL·h.结论 以蛇床子素为内标,RP-HPLC法能够准确、灵敏地测定藁本内酯在大鼠体内的药动学.     

Effects of cerebral ischemia-reperfusion on pharmacokinetic fate of paeoniflorin after intravenous administration of Paeoniae Radix extract in rats

The objective of the present study was to investigate the effects of cerebral ischemia-reperfusion on pharmacokinetics of paeoniflorin after intravenous administration of Paeoniae Radix extract (PRE) in rats. The cerebral ischemia-reperfusion rats were induced by occluding the bilateral carotid arteries of normal rats for 2 h, followed by reperfusion. The resultant animals were immediately administrated by PRE (at a dose of 60 mg/kg of paeoniflorin) via the femoral vein, whilst the same dose was injected to the normal rats. Plasma samples were collected at different time to construct pharmacokinetic profiles by plotting drug concentration versus time. Quantification of paeoniflorin in rat plasma was achieved by using a simple and rapid high-performance liquid chromatographic method. In normal rats, the major parameters of distribution half-life (t1/2alpha), elimination half-life (t1/2beta), area under the plasma concentration-time (AUC), mean retention time (MRT), and clearance (CL), estimated by an open two-compartmental model, were 0.69, 18.77 min, 5338.71 (microg min)/ml, 18.13 min and 0.0162 mg/(kg min), respectively. However, in ischemia-reperfusion rats, the corresponding parameters were 2.04, 24.51 min, 9626.00 (microg min)/ml, 29.75 min and 0.0071 mg/(kg min), respectively. The results showed that ischemia- reperfusion significantly increased AUC values, decreased CL values, and prolonged the terminal half-life of paeoniflorin. These findings suggest that the injuries of ischemia-reperfusion could play an important role in pharmacokinetic process of paeoniflorin.     

Pharmacokinetic Effects of Baicalin on Cerebral Ischemia-reperfusion after iv Administration in Rats

Objective To investigate the pharmacokinetic effects of baicalin on cerebral ischemia-reperfusion (I/R) after iv administration in rats. Methods The cerebral I/R rats were induced by occluding the bilateral carotid arteries of normal rats for 2 h, followed by reperfusion. The resultant animals were immediately iv administrated with baicalin (90 mg/kg), whilst the same dose of baicalin was injected to the normal rats. Plasma samples were collected at different time to construct pharmacokinetic profiles by plotting drug concentration vs time. Quantification of baicalin in rat plasma was achieved using a simple and rapid HPLC method. Results In normal rats, the major parameters of distribution half-life, elimination half-life, area under the plasma concentration-time (AUC), apparent volume of distribution (Vd), and clearance (CL), estimated by an open two-compartmental model, were 0.8868 min, 26.0968 min, 149.6204 mg/min·L, 4.765 L/kg, and 0.5776 L/ kg·min), respectively. However, in I/R rats, the corresponding parameters were 2.084 min, 34.4998 min, 260.0188 μg·min/L, 5.9376 L/kg, and 0.334 L/(kg·min), respectively. Conclusion The cerebral I/R could significantly increase AUC and Vd values, decrease CL values, and prolong the terminal half-life of baicalin. These findings suggest that the injuries of I/R could play an important role in pharmacokinetic process of baicalin.     

Comparative study of pharmacokinetics and tissue distribution of osthole in rats after oral administration of pure osthole and Libanotis buchtormensis supercritical extract

Ethnopharmacological relevance

Libanotis buchtormensis is the source of an important traditional medicine from Shaanxi province of China used in the treatment of many illnesses. Libanotis buchtormensis supercritical extract (LBSE) has analgesic, sedative and anti-inflammatory qualities. Osthole is one of the major bioactive components of LBSE; it is known for its significant anti-tumor, analgesic, and anti-inflammatory properties, it also alleviates hyperglycemia.

Aim of the study

The purpose of the present study was to compare the pharmacokinetics and tissue distribution of osthole in Sprague-Dawley (SD) rats after oral administration of pure osthole and LBSE. The two preparations were administered at the same osthole dose (approximately 130 mg/kg). The results should provide some guidance for the clinical applications of Libanotis buchtormensis.

Materials and methods

Comparative pharmacokinetics and tissue distribution of osthole in SD rats after oral administration of pure osthole and LBSE were analyzed using reversed-phase high-performance liquid chromatography (RP-HPLC). All pharmacokinetic data were analyzed using 3P97 software. Samples of blood and internal organs (heart, liver, spleen, lungs and kidney) were collected and pretreated according to the experimental schedule. After pretreatment, plasma and tissue samples were extracted using ether–ethyl acetate mixture (3:1, v/v). The concentration of osthole in the plasma and tissues were determined using the RP-HPLC method.

Results

The procedure described in this paper shows good precision and stability and is suitable for the osthole assays in biological samples. We found that the average plasma concentration-time profile of osthole after oral administration of osthole and LBSE showed a single peak. There were also clear differences between plasma concentrations of osthole after oral administration of pure osthole and LBSE. Non-osthole ingredients in LBSE showed some pharmacokinetic interactions with osthole and hence decreased its absorption levels (p<0.05). Our results show different tissue distribution of osthole in the single and composite administration regimens.

Conclusions

This study compares the pharmacokinetic characteristics and tissue distribution of osthole in rats after oral administration of pure osthole and LBSE; the results might be useful in clinical application of this traditional Chinese herbal medicine.     

更昔洛韦在家兔体内药动学研究

 目的：了解抗病毒药更昔洛韦静脉注射后在家兔体内的药动学特性。方法：采用高效液相色谱法浏定药物在兔血、尿、组织中浓度的经时变化。结果：家兔静注3种荆童更昔洛韦后血药浓度变化符合开放式三房室模型特征。消除半衰期1.7 h。药物在体内分布广泛，肾脏中血药浓度最高。AUC与剂量呈正相关。24 h尿中原型药物排出黄占给药贡的90.8%。结论：更昔洛韦在家兔体内消除较快，无明显蓄积。     

甘草次酸在大鼠体内药动学的RP-HPLC研究

目的：建立大鼠血浆中甘草次酸浓度的高效液相测定方法，探讨甘草次酸在大鼠体内的药动学过程。方法：大鼠按1.0 mg·kg^-1尾静脉注射甘草次酸后0.08，0.17，0.25，0.33，0.5，0.75，1，2，3，4，6 h眼底采血，乙腈沉淀血浆，HPLC测定血浆中甘草次酸浓度，以DAS软件拟合药动学参数。结果：甘草次酸血药浓度在50～2 000 ng·mL^-1线性良好，r=0.999 7，测得低中高浓度回收率分别为(105.2 ±2.23)%，(102.5±2.95)%，(98.4±2.32)%，日内、日间低中高浓度RSD均小于4%。甘草次酸在大鼠体内药-时曲线符合二室开放模型，主要药动学参数为：t_1/2α=(0.153±0.023) h，t_1/2β=(2.365±0.866) h，C_max =(2.074±0.100) mg·L^-1，CL=(0.715±0.082) L·h^-1·kg^-1，V_d =(2.427±0.872) L·kg^-1，AUC_{0～6 h} =(1.302±0.151) mg·h^-1·L^-1。结论：建立的RP-HPLC适用于体内甘草次酸的含量测定及药代动力学研究，甘草次酸在体内的分布迅速、广泛。     

大鼠体内大承气汤蒽醌成分的药代动力学研究

目的:阐明大承气汤经灌胃给药后,5种游离蒽醌成分在大鼠体内的药代动力学特性。方法:大鼠灌胃给药大承气汤9g/kg后,采集血浆、尿液,采用HPLC法测定血浆中芦荟大黄素、大黄酸、大黄素、大黄酚及大黄素甲醚的含量,并用DAS 2.0软件进行数据分析,计算药动学参数。结果:大鼠灌胃给予大承气汤后,血浆中检测到芦荟大黄素、大黄酸、大黄素、大黄酚及大黄素甲醚,尿中检测到芦荟大黄素、大黄酸,血液和尿液均以芦荟大黄素和大黄酸含量最高。大鼠灌胃大承气汤后,血浆中芦荟大黄素、大黄酸、大黄素、大黄酚及大黄素甲醚的T1/2(Ka)(h)依次是0.36、1.03、1.92、1.89、0.66;T1/2(Ke)(h)依次是0.31、1.17、2.33、2.19、0.81;Cmax(mg/L)依次是48.47、21.69、10.49、5.76、38.76;Tmax(h)依次是4、4、6、4、2;AUC0-t(mg.L-1.h-1)依次是85.73、66.73、65.91、41.84、96.40。结论:大承气汤中蒽醌类成分可以吸收进入体内,其中以芦荟大黄素和大黄酸为主;体内葸醌类成分以尿排泄为主。同时建立经灌胃大承气汤后大鼠血浆中5种游离蒽醌含量的测定方法,并阐明其药动学特性;为大承气汤的体内成分研究提供实验依据。     

羌活提取物中异欧前胡素的药代动力学研究

目的:研究羌活提取物中异欧前胡素的药代动力学规律。方法:用HPLC-荧光检测法测定给药家犬血浆中异欧前胡素的含量,采用药代动力学软件DAS(ver2.0)处理,得到异欧前胡素的药代动力学参数。结果:家犬灌胃给药的异欧前胡素AUC0-9为1.827mg/(L.h),Cm ax为0.835mg/L,Tmax为20m in,t1/2近1.5h.结论:异欧前胡素在家犬体内的代谢过程符合一室模型,吸收、消除较快。     

汉黄芩素白蛋白微球在大鼠体内的药代动力学及组织分布

目的:研究汉黄芩素白蛋白微球在大鼠体内的药动学及组织分布情况.方法:以汉黄芩素溶液为参比,用3P97软件计算大鼠尾静脉给予汉黄芩素白蛋白微球后,其在大鼠体内的药动学模型及药动学参数,用靶向效率评价其在大鼠体内的组织分布及靶向性.结果:汉黄芩素白蛋白微球在大鼠体内的药动学模型符合二室模型,主要药动学参数t1/2α=(0.550 0±0.128 2)h,t1/2β=(14.776 1±1.578 2)h,CL=(0.005 96±0.001 4) mL·h·kg-1,AUC0→∞＝(126.331 7±9.501 2) ng·h·L-1.其在肝脏,脾脏,心脏,肺脏及肾脏的靶向效率分别为2.21,2.02,0.58,0.64,0.26.结论:与汉黄芩素溶液相比,汉黄芩素白蛋白微球能提高对肝脏,脾脏的趋向性,有利于提高其治疗作用.     

银杏内酯B注射液大鼠药代动力学研究

目的:研究大鼠静脉注射银杏内酯B注射液后的药代动力学。方法:采用LC-MS法测定银杏内酯B经时血药浓度,采用DAS2.0实用药代动力学程序计算其药代动力学参数。结果:大鼠单次静脉注射低、中、高(0.75、3.75、14.0 mg/kg)三个剂量银杏内酯B注射液,银杏内酯B主要药代动力学参数:Tmax均为(0.083±0)h,Cmax均值分别为(422.312±14.203)、(1608.467±226.677)、(1987.036±237.202)μg/L,AUC0-t均值分别为(533.833±114.943)、(1786.029±137.066)、(1943.44±415.892)μg.h/L。结论:各剂量组血药浓度试验数据经拟和优度分析,药物消除符合三室模型,AUC0-t、AUC0-∞、Cmax随剂量的增加而不成比例增加,说明银杏内酯B注射药液给药后在大鼠体内呈非线性动力学消除过程。