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。     

姜黄素纳米结构脂质载体的药动学

目的建立测定大鼠血浆中姜黄素的HPLC法,并研究姜黄素纳米脂质体大鼠灌胃给药后的药动学行为。方法 12只SD大鼠随机分成2组,单剂量灌胃给予纳米脂质体及游离姜黄素后,采用HPLC法测定血浆中药物浓度,计算药代动力学参数。结果建立了姜黄素在大鼠血浆中的测定方法。结果表明纳米脂质体在大鼠体内吸收迅速,清除率降低,其AUC(0-t)为(930.08±18.95)μg·h/L,t1/2为(10.71±3.30)h,Cmax为(117.57±4.61)μg/L,相对于游离药物,纳米脂质体的生物利用度提高了约800%。结论纳米脂质体是姜黄素较好的递送系统,HPLC法可用于大鼠血浆姜黄素测定及药代动力学研究。     

HPLC-UV法测定大鼠血清中柴胡皂苷C浓度

目的:建立大鼠血清中柴胡皂苷C的HPLC血药浓度测定方法,并用于柴胡皂苷C在大鼠体内药代动力学的研究。方法:大鼠血清样品采用甲醇沉淀蛋白,HPLC法测定血药浓度。色谱柱为Waters C18柱(4.6mm×250mm,5μm),流动相为乙腈-0.1%磷酸水梯度洗脱,流速为1.0ml/min,检测波长为210nm。测定大鼠单次腹腔注射528mg/kg后血药浓度,采用DAS2.0药动学分析软件拟合主要药动学参数。结果:大鼠血清中柴胡皂苷C在58.4~7300mg/L浓度范围内线性关系良好,该成分的最低检测浓度(S/N=3)为14.6mg/L,平均回收率在85%以上,日内、日间精密度及稳定性的RSD8%。大鼠单次腹腔注射528mg/kg后,主要药动学参数t1/2z、AUC0-t、MRT0-t分别为(1.25±0.84)h、(943.79±39.16)h/(mg·L)、(0.91±0.05)h。结论:该方法简便、准确,可作为柴胡皂苷C血药浓度定量分析方法,并能满足其在大鼠体内的药代动力学研究。     

UPLC-MS/MS法测定青蒿琥酯在溃疡性结肠炎模型大鼠体内的药代动力学

目的:建立快速灵敏、高效的超高效液相色谱-串联质谱(UPLC-MS/MS)法,分析青蒿琥酯(artesunate,ART)在溃疡性结肠炎模型大鼠体内药代动力学参数差异。方法:将12只SD大鼠随机分为正常组和模型组,模型组采用0.5 mL含20～30 mg(100 mg/kg)TNBS的30%乙醇溶液灌肠法造模。采用UPLC-MS/MS法进行方法学考察与血药浓度分析,色谱柱为安捷伦Poroshell 120EC-C18色谱柱(100 mm×2.1 mm,2.7μm);流动相为乙腈-0.01%甲酸;洗脱方式为梯度洗脱,柱温为40℃;流速为0.5 mL/min;质谱离子源为ESI电喷雾离子源,正离子模式进行血药浓度检测,用DAS 2.0软件计算主要药代动力学参数。结果:建立了UPLC-MS/MS测定大鼠血浆中ART浓度的方法,线性范围为21.47～15,652.00 ng/mL(R2=0.999,5),最低检测限为1.25 ng/mL(S/N3)。测得经口服给药后,ART在大鼠体内的代谢符合二室模型,正常大鼠和溃疡性结肠炎大鼠模型的药物峰浓度(Cmax)分别为(1,273.24±192.73)μg/L、(829.86±177.52)μg/L,药物时间曲线下面积(AUC0～8 h)分别为(2,435.02±558.01)μg/(h·L)、(1,523.95±482.81)μg/(h·L),半衰期(t_(1/2))分别为(2.83±1.94)h、(5.04±1.28)h。其中,溃疡性结肠炎大鼠的C_(max)明显降低(P0.01),AUC0～8 h减少(P0.05),t1/2明显升高(P0.05)。结论:建立了一种快速灵敏、高效的测定大鼠血浆中ART浓度的方法;并应用这种方法测得经口服给药后,青蒿琥酯在正常大鼠和溃疡性结肠炎模型大鼠体内药代动力学参数存在差异,提示了病理状态下动物吸收率对药物作用的影响。     

HPLC-荧光检测法测定大鼠血浆中大黄酸的浓度及其药代动力学

目的:建立测定大鼠血浆中大黄酸浓度的HPLC荧光检测方法,并对大黄酸在大鼠体内的药代动力学行为进行研究。方法:血浆样品经乙醚萃取后,用HPLC荧光法(HPLCFLD法)进行测定分析。色谱柱为C18Hypersil,ODS2,5μm,250mm×4.6mmID,流动相为0.5%的冰醋酸-乙腈-甲醇(27∶10∶60),检测激发波长440nm,发射波长520nm,同时测定大鼠单次灌胃大黄酸70mg/kg后血药浓度,并利用DAS软件拟合其药代动力学参数。结果:大黄酸的血药浓度在0.052～80μg/mL范围内线性关系良好,最低检测限为2ng/mL,以质控样品计算,在各浓度水平下,此法的回收率均大于85%,日间和日内精密度小于15%,符合生物样品分析要求。大鼠灌胃大黄酸70mg/kg后,血药浓度-时间曲线呈二室模型。主要药动学参数Tmax,Cmax,AUC(0-t),MRT,T1/2α,T1/2β分别为0.50±0.27h,54.64±11.60μg/mL,164.29±44.77μg/h·mL,4.03±0.46h,1.48±0.77h,3.68±1.42h。结论:该法操作简便、快速、灵敏,适用于对微量生物样品进行大批量测定。     

大鼠口服苦杏仁苷组织分布和血浆药物代谢动力学研究

目的:明确大鼠口服苦杏仁苷的组织分布和血浆药代动力学参数。方法:体内药物分析采用高效液相色谱法(HPLC),使用Thermo BDS Hypsil C18色谱柱(柱长25cm,内径0.46cm,粒径5μm),乙腈-0.1%磷酸水溶液(8:92,v/v)为流动相,检测波长207nm,流速1.0m L/min,柱温25℃,进样量10μL,共分析实验动物(大鼠)血浆、心脏、肝脏、脾脏、肺、肾脏中苦杏仁苷的含量,并测定该成分的血浆药代动力学参数。结果:苦杏仁苷在上述器官组织中的含量分别为44.774±7.397ng/m L、23.693±6.097ng/g、43.391±5.963ng/g、53.745±6.584ng/g、309.335±13.662ng/g、55.373±4.467ng/g,血浆中Tmax为0.25h,Cmax为93.871ng/m L,T1/2为1.21h,MRT为1.91h,AUC0-i为73.595hμg/m L,AUC0-∞为74.133hμg/m L。结论:口服苦杏仁苷后,苦杏仁苷集中分布于肺组织中,同时本研究所用方法能够快速、准确对该化合物的体内代谢情况进行评价。     

大鼠口服右旋布洛芬及右旋布洛芬精氨酸盐后右旋布洛芬的药动学

 目的 建立测定大鼠血浆中右旋布洛芬的LC-MS/MS方法,并用于研究大鼠口服右旋布洛芬和右旋布洛芬精氨酸盐后右旋布洛芬的药动学。方法 大鼠单次口服右旋布洛芬和右旋布洛芬精氨酸盐,于给药后不同时间采集血样,血浆样本经沉淀蛋白后,以吲哚美辛为内标,LC-MS/MS测定血浆中右旋布洛芬的浓度。结果 大鼠口服右旋布洛芬和右旋布洛芬精氨酸盐后右旋布洛芬均迅速吸收;大鼠口服右旋布洛芬精氨酸盐后血浆中右旋布洛芬的AUC,较其口服等剂量右旋布洛芬后的AUC明显增大。结论 右旋布洛芬和精氨酸成盐后其生物利用度增加。     

当归腹痛宁滴丸中藁本内酯的测定及大鼠体内的药动学

目的了解市售当归腹痛宁滴丸中藁本内酯的量及口服后藁本内酯在大鼠体内的药动学。方法用气相色谱法测定当归腹痛宁滴丸中藁本内酯的量,SD大鼠灌胃给药,在设定的时间点采血0.3 mL,离心分离血浆,HPLC法测定藁本内酯的血药浓度,计算药动学参数,与藁本内酯静脉注射给药比较,对其在大鼠体内的药动学特征进行评价。结果当归腹痛宁滴丸中藁本内酯的量为0.19 mg/粒。当归腹痛宁滴丸灌胃给药后,藁本内酯25 mg/kg组,其Cmax为(620.395±47.69)μg/L,Tmax0.08 h,AUC(0-∞)(709.346±77.775)μg/L·h,t1/2z(4.331±1.278)h;12.5 mg/kg组Cmax为(173.902±13.654)μg/L,Tmax0.08 h,AUC(0-∞)(365.003±72.813)μg/L·h,t1/2z(2.236±0.188)h;静脉注射藁本内酯25 mg/kg后Cmax(675.965±41.968)μg/L,Tmax0.08 h,AUC(0-∞)(949.501±63.182)μg/L·h,t1/2z(3.085±0.137)h;静脉注射12.5 mg/kg时Cmax(391.402±25.251)μg/L,Tmax0.08 h,AUC(0-∞)(391.078±26.609)μg/L·h,t1/2z(2.985±0.241)h。结论当归腹痛宁滴丸口服,其有效成分藁本内酯胃肠道吸收迅速,生物利用度高,给药后药时曲线呈双吸收峰,可能与滴丸中藁本内酯释放特征有关。     

氧化苦参碱在大鼠体内药代动力学特征

目的 建立大鼠血浆中氧化苦参碱的HPLC检测方法,考察氧化苦参碱大鼠口服后药代动力学特征.方法 分别给予大鼠静脉注射和灌胃氧化苦参碱后,于不同时间点采血,血浆经处理后采用HPLC方法进行检测,条件为:C18柱,柱温30℃,流动相0.1 mol/L KH2PO4水溶液-乙腈(93∶7),用H3PO4调pH 2.5.结果 氧化苦参碱在50～100μg/mL范围内线性关系良好(r=0.999 2),日内和日间RSD均小于5.2％,回收率大于88.67％;氧化苦参碱静注后AUC 19.92μg/(mL·h),t1/2 1.33 h;口服AUC 9.27μg/(mL·h),t1/2 1.89 h,Cmax为2.28μg/mL,tmax1.89 h,绝对生物利用度9.31％.结论 该法灵敏、简单、专属性强,可用于大鼠血浆中氧化苦参碱的测定.氧化苦参碱在大鼠体内的生物利用度较低.     

L-缬氨酸薯蓣皂苷元酯的药代动力学和口服生物利用度

目的研究新化合物L-缬氨酸薯蓣皂苷元酯在大鼠体内的药代动力学和口服生物利用度。方法建立RPHPLC法检测大鼠血浆中的L-缬氨酸薯蓣皂苷元酯,考察经灌胃和静脉给予40 mg/kg该成分后血药浓度的变化。采用DAS 2.0软件计算药代动力学参数和口服生物利用度。结果灌胃组大鼠的Cmax为(9.8±0.5)μg/m L,Tmax为(32.9±5.7)min,T1/2为(60.1±10.2)min,AUC为(1.5±0.4)×103μg·min/m L;静脉注射组的T1/2为(74.6±16.5)min,AUC为(1.2±0.3)×104μg·min/m L。结论 L-缬氨酸薯蓣皂苷元酯的口服生物利用度为12.5%,高于文献报道4.3%。     

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??OBJECTIVE To develop an LC-MS/MS method for the quantitative analysis of ocotillol in rat plasma, and study the pharmacokinetic characteristics of ocotillol in rats after oral administration.METHODS Ocotillol was extracted from plasma sample by protein precipitation. The concentration of ocotillol in plasma was determined by LC-MS/MS and the plasma concentration-time curve and main pharmacokinetic parameters were calculated after a single oral administration of ocotillol at 40 mg??kg^-1 to SD rats.RESULTS Excellent linearity was found between 10-240 ng??mL^-1. Intra-and inter-day precision values (RSDs) of QC samples were both below 15% and the extraction recoveries of ocotillol from plasma were higher than 84.14%. Double peaks were observed in the mean plasma concentration versus time profile of ocotillol after oral administration. The main pharmacokinetic parameters of ocotillol were as follows:the mean maximum plasma concentration (??_max) was (156.60??51.84) ng??mL^-1 occurring at (0.83??0.26) h post dose, the mean elimination half-time (t_1/2) was (8.82??7.56) h, and the mean area under the plasma concentration versus time curve (AUC_0-t) was (687.15??144.08) ng??h??mL^-1.CONCLUSION The current data shows that ocotillol is rapidly absorbed in rats after oral administration and slowly eliminated from circulatory blood system, with low plasma exposure. Enterohepatic circulation may contribute to the atypical drug absorption profiles.     

电针“足三里”对对乙酰氨基酚药代动力学的影响

目的:观察电针对大鼠口服对乙酰氨基酚后体内药代动力学变化,探讨针药结合效应及作用机制。方法:48只SD大鼠,雌雄各半,随机分为对乙酰氨基酚低、中、高剂量组(分别口服对乙酰氨基酚300、600、1200mg/kg),以及电针+对乙酰氨基酚低、中、高剂量组(分别口服对乙酰氨基酚300、600、1200mg/kg后即刻电针"足三里"穴位20min),共6个组。每组大鼠单剂量口服对乙酰氨基酚后于不同的间隔时间取血,采用RP-HPLC法测定其血浆药物浓度,采用3P87药代动力学程序软件计算其药动学参数,观察电针对对乙酰氨基酚吸收和代谢的影响。结果:除了电针+对乙酰氨基酚高剂量组显示为非线性动力学特征外,其余5组大鼠体内对乙酰氨基酚药代动力学过程均呈一级吸收的二室开放模型。与对乙酰氨基酚低、中剂量组相比,电针+对乙酰氨基酚低、中剂量组达峰时间(Tmax)提前(P0.01,P0.05),血药峰浓度(Cmax)显著增高(P0.01);吸收半衰期(T1/2ka)明显加快(P0.01,P0.05),但消除半衰期(T1/2ke)基本不变(P0.05);曲线下面积(AUC)显著性增大(P0.01),药物清除率(Cl(s))则减慢(P0.01)。与对乙酰氨基酚高剂量组相比,电针+对乙酰氨基酚高剂量组AUC显著性增大(P0.01),平均滞留时间(MRT)则相对延长(P0.05)。结论:临床针药并用时,必须考虑药物剂量的大小,以及电针对某些药物代谢可能产生的影响,以防引起不良反应的发生。     

多索茶碱与莫西沙星在大鼠体内药动学的相互作用

 目的考察多索茶碱和莫西沙星在大鼠体内的药动学特性及合用时的相互作用。方法采用高效液相色谱法测定大鼠给药后不同时间的多索茶碱和莫西沙星的血浆浓度。血浆浓度 时间数据用非线性程序WINNONLIN拟合，求得药动学参数。结果两药合用与单独用药时的药-时曲线基本一致,多索茶碱呈一级吸收一级开放式模型，莫西沙星呈一级吸收二室开放式模型，药动学参数无统计学差异。但多索茶碱与莫西沙星合用时，多索茶碱的代谢产物之一茶碱的AUC约是单用多索茶碱时的2倍。结论两药合用药动学上无明显的相互作用, 但莫西沙星有减慢多索茶碱的代谢产物茶碱代谢的趋势，两药可以同时服用，但应注意监测茶碱的血药浓度。     

高蛋白高脂肪高碳水化合物饲料对大鼠地西泮、美芬妥英代谢影响

 目的:研究高蛋白、高脂肪、高碳水化合物饲料对大鼠地西泮、美芬妥英的体内代谢，以了解饮食因素对药牡氧化代谢的影响。方法:HPLC测定用药后不同时间血浆药物及其代谢产物浓度，用3P87程序处理数据，求得药动学参数。结果:与对照组相比，高蛋白饮食使地西浮t _1/2β缩短，AUC降低，Cls增高;使地西浮的代谢产物去甲地西泮的AUC增高;使尿液中S/R-美芬妥英比值明显降低。结论:高蛋白饮食加快地西泮的去甲基化反应，增强S-美芬妥英羟化代谢。     

Cholesterol-lowering activity of the aqueous extract of Spergularia purpurea in normal and recent-onset diabetic rats

The purpose of this study was to examine the effect of single and repeated oral administration of the aqueous extract of Spergularia purpurea (SP) at a dose of 10mg/kg in normal and streptozotocin-induced diabetic rats. In normal rats, the aqueous extract of SP induced a significant decrease of the plasma cholesterol concentrations 6h after a single oral administration (P<0.05) and 2 weeks after repeated oral administration (P<0.05). The plasma triglycerides levels increased significantly 6h after a single oral administration (P<0.05) and decreased 2 weeks after repeated oral administration (P<0.05). In diabetic rats, SP treatment caused a significant decrease of plasma cholesterol levels after a single (P<0.01) and repeated (P<0.01) oral administration. A significant increase of triglycerides levels was observed 6h after a single oral administration of the SP aqueous extract (P<0.01). One week after repeated oral administration of SP aqueous extract, the plasma triglycerides levels were significantly decreased (P<0.005) and still dropped after 2 weeks (P<0.01). On the other hand, the repeated oral administration of SP aqueous extract caused a significant decrease of body weight after 2 weeks of treatment in both normal (P<0.001) and diabetic (P<0.01) rats. We conclude that the aqueous extract of SP exhibits a cholesterol and body weight-lowering activities in both normal and severe hyperglycaemic rats.     

Hypoglycemic effect of Equisetum myriochaetum aerial parts on streptozotocin diabetic rats

The hypoglycemic effect of water as well as butanolic extracts prepared from aerial parts of Equisetum myriochaetum (Equisetaceae) was examined in streptozotocin induced diabetic rats. A single oral administration of the water extract (WE) at doses of 7 and 13 mg/kg and of the butanol extract (BE) at doses of 8 and 16 mg/kg significantly (P<0.001) lowered the plasma glucose levels in diabetic rats after three hours of the administration. As a reference drug glibenclamide was used and showed, at a dose of 3 mg/kg, similar hypoglycemic effect like the tested extracts. Three kaempferol glucosides and one caffeoyl glucoside were isolated from the drug and were shown to be the main constituents in both extracts.     

Study of hypoglycaemic and hypolipidemic effects of Inula viscosa L. aqueous extract in normal and diabetic rats

The present study was designed to examine the hypoglycaemic and hypolipidemic activity of Inula viscsa aqueous extract on normal and diabetic rats. In normal rats, a significant reduction in blood glucose levels 2 h was observed after a single oral administration (p<0.001). Repeated daily oral administration significantly reduced blood glucose levels after 4 days of treatment (p<0.01). In diabetic rats, a significant reduction in blood glucose levels was observed 1 h after a single oral administration (p<0.001). Repeated oral administration reduced blood glucose levels at the 4th day (p<0.001). No change in total plasma cholesterol and triglyceride levels was observed after both a single and repeated oral administration in both normal and diabetic rats. In addition, plasma insulin levels and body weight remained unchanged after 15 days of repeated oral administration in normal and diabetic rats. We conclude that Inula viscosa possess a hypoglycaemic but not hypolipidemic activity in normal and diabetic rats. The observed hypoglycaemic activity seems to be independent of insulin secretion.     

Effect of Retama raetam on lipid metabolism in normal and recent-onset diabetic rats

The purpose of this study was to examine the effect of single and repeated oral administration of the aqueous extract of Retama raetam (Forssk) Webb (RR) (20 mg/kg) on lipid metabolism in normal and streptozotocin-induced diabetic rats. In normal rats, the aqueous extract of RR induced a significant decrease of the plasma triglycerides concentrations one week after repeated oral administration (P<0.05). This reduction was maintained two weeks after once daily repeated oral administration (P<0.05). A significant decrease of plasma cholesterol levels was also observed one week (P<0.05) and two weeks (0.05) after repeated oral administration.

In diabetic rats, RR treatment caused a significant decrease of plasma triglycerides levels after a single (P<0.05) and repeated (P<0.001) oral administration. A significant decrease of cholesterol levels was observed four hours after a single oral administration of the RR aqueous extract (P<0.05). One week after repeated oral administration of RR aqueous extract, the plasma cholesterol levels were significantly decreased (P<0.05) and still dropped after two weeks (P<0.005).

On the other hand, the repeated oral administration of RR aqueous extract caused a significant decrease of body weight one week after repeated oral treatment in diabetic rats (P<0.05). We conclude that the aqueous extract of RR exhibits lipid and body weight lowering activities in both normal and severe hyperglycemic rats after repeated oral administration of RR aqueous extract at a dose of 20 mg/kg.