阿霉素对去甲斑蝥素在大鼠体内药动学的影响

目的研究大鼠静脉给予阿霉素（ADM）对去甲斑蝥素（NCTD）体内药物动力学的影响。方法用HPLC-MS方法测定ADM和NCTD合并给药与NCTD单独给药大鼠血浆中的NCTD浓度,比较两者的药动学参数。结果ADM和NCTD合并给药组与NCTD单独给药组相比在分布速度常数（α）、分布相半衰期（t1/2α）、中央室向周边室的转运速度常数（k12）3个药动学参数有统计学差异（P〈0.05）,其余药动学参数之间无显著差异（P〉0.05）。结论NCTD与ADM合用时,ADM不会显著影响NCTD在大鼠体内的药动学过程,两药合用增效的原因主要在于药效学上的协同作用。     

绿原酸联用阿霉素犬的药物动力学研究

目的 研究给予Beagle犬绿原酸和阿霉素后犬体内阿霉素的药物物动力学规律.方法 Beagle犬被随机分为阿霉素组和联合用药组.静脉给药后采集血样,制备血清,以HPLC法测定血药浓度.色谱柱为Aichrombond-AQ C18(150 mm×4.6mm,5μm),流动相为0.01 mol·L-1 KH2PO4-甲醇-乙腈-甲酸(50:40:10:0.1),流速1.0 mL·min-1,波长254 nm.结果 阿霉素0.011～11.4 μg·mL-1(r=0.9990)与峰面积的线性关系良好,最低检测浓度为5.25 ng·mL-1.联合用药前后阿霉素均呈二室模型;Cmax为0.457、0.557 mg·L-1,Tmax为15、15 min,T1/2为18.70、22.79 min,Cl为0.029、0.027 L·min-1·kg-1,AUC为54.99、59.53 mg·L-1·min-1,相对生物利用度为115.40%.结论 联合用药后,绿原酸对阿霉素的药物动力学模型无显著影响,但阿霉素清除率略有下降,半衰期及AUC增加,生物利用度明显提高(P<0.05).绿原酸与阿霉素联合用药,可提高阿霉素的治疗浓度,且半衰期略有增长.     

地尔硫卓与美托洛尔在家兔体内的药动学相互作用研究

本文选用６只家兔进行随机交叉实验，对家兔单用地尔硫　、美托洛尔及合用两药时的药动学过程作了比较。发现合用两药后，美托洛尔的Ｋ＿ｅ、Ｃｌ＿ｓ均较单用时小（Ｐ＜０．０５），Ｃ＿ｍａｘ和ＡＵＣ＿（０－∞）则明显增大。地尔硫的Ｋ＿ｅ在合用药时显著增大，其活性代谢物去乙酰地尔硫的Ｃ＿ｍａｘ和ＡＵＣ＿（０－∞）则也有显著提高。表明合用两药后美托洛尔的肝脏代谢受到抑制。本文证实的相互作用提示，临床合用两药时应同时监测患者血浓，并适当调整剂量，以免发生不良反应。     

醋酸地塞米松对替硝唑大鼠体内药动学的影响

目的：探讨醋酸地塞米松对替硝唑大鼠体内药动学的影响。方法：大鼠随机分为两组,每组5只,一组灌胃给予替硝唑,另一组灌胃给予醋酸地塞米松,连续5d,于第6天合并给药替硝唑与醋酸地塞米松,分别测定两组大鼠血浆中替硝唑的浓度,用DAS软件程拟合药动学参数。结果：单独给予替硝唑组和联合给药组的替硝唑的主要药动学参数：Cmax分别为（27．08±2．98）和（23．69±3．45）mg·L^-1,t1／2：（2．16±0．76）h和（1．95±0．31）h,AUC0-24h（138．04±5．84）和（119．90±11．46）mg·h·L^-1。两组间AUC及CL／F的差异有统计学意义（P〈0．05）。结论：醋酸地塞米松对替硝唑大鼠体内药动学过程影响较小。     

洛沙坦的药动学特点及药物相互作用

洛沙坦的药动学特点及药物相互作用郭胜才冯友根（中国人民解放军第１１７医院杭州３１００１３）肾素－血管紧张素－醛固酮系统是重要的血压调节系统。临床上常用的血管紧张素转化酶抑制剂，能抑制血管紧张素Ⅰ转换成血管紧张素Ⅱ，使血管舒张，血压降低，具有一定的治疗...     

盐酸阿霉素及其脂质体在大鼠体内的相关药动学参数比较

目的 比较盐酸阿霉素脂质体与盐酸阿霉素在大鼠体内的血药浓度及相关药动学参数。方法 采用HPLC法,测定大 鼠经尾静脉注射盐酸阿霉素或盐酸阿霉素脂质体注射液[0.8 mg·(100 g)-1体重]后,在大鼠体内的血药浓度,得出药-时曲线图及相关药动学参数,并将血药浓度经SPSS10.0统计软件进行配对t检验。结果 在大鼠体内,阿霉素脂质体血药浓度200倍于阿霉素血药浓度;阿霉素脂质体药时曲线下面积AUC较阿霉素大,表观分布容积Vc较阿霉素小,清除率Cl(s)较阿霉素慢;阿霉素与阿霉素脂质体在大鼠体内的血药浓度具有显著性差异(P<0.05)。结论 阿霉素制成脂质体可延长其在血浆中的停留时间,降低血管外分布量,减慢清除。可望提高药效、降低心脏的不良反应。     

芹菜素对阿霉素在大鼠体内药动学的影响

目的：研究不同剂量芹菜素对阿霉素在大鼠体内药动学过程的影响。方法：实验设单独给药组和联合给药组,其中单独给药组大鼠给予阿霉素注射液4 mg·kg^-1,经快速静脉注射;联合组大鼠经腹腔注射以不同剂量（7.5,15,30 mg·kg^-1）芹菜素预处理5 d后,快速静脉注射阿霉素注射液4 mg·kg^-1。采用HPLC法测定大鼠血浆及胆汁中阿霉素的浓度,经DAS2.0数据处理软件计算药动学参数。结果：阿霉素单独给药及与不同剂量芹菜素联合给药后,均符合二室模型。研究发现与单独给药组比较,中、高剂量芹菜素联用后阿霉素的药动学参数发生明显改变,分布半衰期（t_1/2α）和清除率（CL）显著降低,而药-时曲线下面积（AUC）和平均滞留时间（MRT）显著增加,消除相半衰期（t_1/2β）延长。与单独组相比,联用组经胆汁的累计排泄量降低,且随剂量增加差异具有统计学意义。结论：中、高剂量芹菜素可显著改变阿霉素的体内药动学过程,其原因可能是芹菜素抑制由MRP1和P-gp所介导的药物外排。     

达沙替尼与槲皮素在大鼠体内药动学相互作用特征

目的:探讨达沙替尼与槲皮素联用后在大鼠体内药动学相互作用特征。方法:将大鼠随机分为3组,分别灌胃给药达沙替尼3.5 mg·kg^-1、槲皮素35 mg·kg^-1、达沙替尼3.5 mg·kg^-1+槲皮素35 mg·kg^-1,连续给药14 d,于第15天给药后不同时间点眼眶采血,离心获取上层血浆。采用酶解法处理血浆样品,建立高效液相色谱串联质谱(HPLC-MS/MS)法同时检测血浆中的达沙替尼与槲皮素,描绘平均血药浓度-时间曲线,通过DAS 3.2.2软件对药动学参数进行分析。结果:达沙替尼单用与联用状态下主要药动学参数如下,AUC_0-t:(0.28±0.035),(0.49±0.051)μg·h·mL^-1;AUC_0-∞:(0.29±0.035),(0.51±0.047)μg·h·mL^-1;MRT_0-t:(7.74±0.31),(7.44±0.25) h; MRT_0-∞:(8...     

阿霉素在恶性淋巴瘤患者体内的药代动力学研究

目的 :了解恶性淋巴瘤患者阿霉素血药浓度和药代动力学特点及其临床意义。方法 :2 6例恶性淋巴瘤患者均采用CHOP方案化疗。血药浓度测定用HPLC法。结果 :化疗有效 (CR PR) 18例 ( 6 9.2 % ) ,无效 8例( 30 .8% )。化疗有效组与无效组的平均血药峰浓度分别为 196 5 .3ng·ml-1和 1177.8ng·ml-1,K12 分别为 2 .6 2 1h-1和 1.76 1h-1,Vc分别为 5 2 6L·m-2 和 8.34L·m-2 ,差异均具有显著性 (P <0 .0 5 )。不同个体间血药浓度和药代动力学差异很大 ,变异系数 36 .5 %～ 75 .8%。结论 :恶性淋巴瘤患者阿霉素血药浓度测定及药代参数分析对预测疗效 ,实行个体化给药方案有一定的临床指导意义     

Pharmacokinetics and brain penetration study of chlorogenic acid in rats

1. The present study is designed to investigate the brain distribution and plasma pharmacokinetics profiles of chlorogenic acid (CGA) after intranasal administration in Charles–Foster rats to evaluate whether the CGA molecules are transported directly via the nose-to-brain path.

2. The CGA is administered intravenously (IV) and intranasally (IN) at the dose of 10?mg/kg. Further, its concentration in the plasma, cerebrospinal fluid (CSF) and the whole brain is analyzed by HPLC-UV method.

3. The study observes that CGA is rapidly absorbed in plasma with t_max of 1?min similar to IV route after IN administration. The peak plasma concentration and AUC_0–24 are higher by 3.5 and 4.0 times respectively in IV administration, compared to IN delivery that represents the significant less systemic exposure of CGA in IN route.

4. However, the concentration of CGA in the brain is 4, 6.5, 5.3, 5.2 and 4.5 times higher at 30, 60, 120, 240 and 360?min, respectively in IN administration compared to IV administration. The exposure of CGA in the brain after IN administration (AUC_{brain, IN}) was significantly greater (4 times) as compared to the exposure of CGA in the brain (AUC_{brain, IV}) after IV administration reflecting significant brain uptake of CGA through nasal route. Therefore, IN delivery of CGA can be a promising approach for the treatment of stroke and neurodegenerative disorders.     

金银花提取物中绿原酸在大鼠体内药动学和生物利用度的研究

目的:研究金银花提取物经不同途径给药后绿原酸在大鼠体内的药动学和绝对生物利用度。方法:建立大鼠血浆中绿原酸的HPLC-MC/MC检测方法。考察大鼠分别经静脉注射(iv)、肌内注射(im)及灌胃(ig)给药后血药浓度变化。用WINNONLIN 6.1软件计算药动学参数,根据药-时曲线下面积AUC_0-∞和给药剂量计算肌注和灌胃金银花提取物中绿原酸的绝对生物利用度。结果:大鼠经静脉注射、肌内注射和灌胃金银花提取物后,绿原酸在大鼠体内代谢过程均符合二室模型,消除半衰期分别为(0.44±0.08)、(0.50±0.12)、(0.38±0.11)h;AUC_0-∞分别为(6931.62±1528.35)、(6550.34±1025.41)、(2591.87±784.21) μg·h·L^-1。灌胃和肌注金银花提取物后其绿原酸的绝对生物利用度分别为37.39%和94.50%。结论:肌内注射与静脉注射金银花提取物在大鼠体内的药动学过程类似,肌注给药的生物利用度较高,灌胃生物利用度低,该结果可以为金银花提取物的给药途径和剂型研究提供科学依据。     

银黄注射液及口服液中绿原酸和黄芩苷在大鼠体内的药动学比较

目的 比较银黄注射液和银黄口服液中绿原酸和黄芩苷在大鼠体内的的药物动力学特征.方法 10只(6)大鼠随机均分成两组,分别iv银黄注射液和ig银黄口服液,用HPLC同时测定不同时间点血浆中绿原酸和黄芩苷的浓度.结果 大鼠iv银黄注射液后,血浆中能够同时检出绿原酸和黄芩苷,其中绿原酸的呈三室开放模型,黄芩苷的药-时曲线变化呈二室开放模型;大鼠ig银黄口服液后,血浆中检不出绿原酸,而黄芩苷的药-时曲线呈多峰现象,其绝对生物利用度为15.2%.结论 不同的给药途径,绿原酸和黄芩苷在大鼠体内所表现的药物动力学特征相差很大.     

Pharmacokinetics and excretion of chlorogenic acid in beagle dogs

In order to characterize the pharmacokinetics and excretion of chlorogenic acid (ChA) in beagle dogs, a gradient high performance liquid chromatographic method has been developed and validated for determining ChA concentration in dog serum, urine and feces. The pharmacokinetic profile of ChA in dog after an intravenous injection was best described by a two-compartment model. Terminal half-lifes were similar at dosages of 5, 20 and 50 mg/kg, ranging from 41-45 min, while AUC and Cmax values of ChA were dose proportional. There are no differences in Vd and CL at three doses of ChA, ranging from 133-252 mL/kg and from 4.4-6.3 mL/min/kg respectively. Excretion studies showed that more than 67% ChA was excreted into urine and less than 3% ChA was eliminated into feces.     

双黄连粉针中绿原酸在大白鼠中的药物动力学

目的:研究双黄连粉针在大鼠体内的药物动力学.方法:采用HPLC法测定大鼠血浆中双黄连粉针中绿原酸的血药浓度.流动相甲醇:磷酸缓冲液(pH2.7)(10:90),色谱柱ERC-ODS-1161(6mm×100mm),紫外检测波长274nm,柱温55℃,流速1ml/min.结果:当剂量为60mg/kg时,药物动力学参数为Vc=0.09L,Ke=0.68/h,K_(12)=2.66/h,K_(21)=1.67/h,T_(1/2)=1.14h,α=4.77h~(-1),β=0.55h~(-1),AUC=1.73μg·h/ml.结论:双黄连粉针中绿原酸在大白鼠体内呈二室模型分布.     

脉络宁注射液中绿原酸在健康人体内的药动学

目的：研究单剂量和多剂量静脉滴注脉络宁注射液中绿原酸在健康人体内的药动学。方法：10名健康受试者单、多次剂量静脉滴注脉络宁注射液后,采用高效液相色谱．质谱联用法（LC／MS／MS）测定血浆中绿原酸浓度,DAS（1．0）软件对其药．时曲线进行拟合,并计算药动学参数。结果：绿原酸药．时曲线符合二房室模型,单、多次剂量主要药动学参数分别为Cmax：（252±66）、（262±87）μg／L;t1/2β：（1．35±0．53）、（1．37±0．27）h;V：（0．70±0．24）、（0．68±0．24）L／kg;CL：（0．37±0．10）、（0．34±0．11）L·kg^-1·h^-1;AUG0-tn：（404±110）、（455±151）μg·L^-1·h。结论：单剂量和多次静脉滴注脉络宁注射液后绿原酸主要药动学参数经统计学处理差异无统计学意义;连续多次给药后,绿原酸体内无蓄积现象,绿原酸的体内过程不受性别差异的影响。     

Pharmacokinetics of chlorogenic acid and corydaline in DA-9701, a new botanical gastroprokinetic agent,in rats

Abstract

1.?Few studies describing the pharmacokinetic properties of chlorogenic acid (CA) and corydaline (CRD) which are marker compounds of a new prokinetic botanical agent, DA-9701, have been reported. The aim of the present study is to evaluate the pharmacokinetic properties CA and CRD following intravenous and oral administration of pure CA (1–8?mg/kg) or CRD (1.1–4.5?mg/kg) and their equivalent dose of DA-9701 to rats.

2.?Dose-proportional AUC and dose-independent clearance (10.3–12.1?ml/min/kg) of CA were observed following its administration. Oral administration of CA as DA-9701 did not influence the oral pharmacokinetic parameters of CA. Incomplete absorption of CA, its decomposition in the gastrointestinal tract, and/or pre-systemic metabolism resulted in extremely low oral bioavailability (F) of CA (0.478–0.899%).

3.?CRD showed greater dose-normalized AUC in the higher dose group than that in lower dose group(s) after its administration due to saturation of its metabolism via decreased non-renal clearance (by 51.3%) and first-pass extraction. As a result, the F of CRD following 4.5?mg/kg oral CRD (21.1%) was considerably greater than those of the lower dose groups (9.10 and 13.8%). However, oral administration of CRD as DA-9701 showed linear pharmacokinetics as a result of increased AUC and F in lower-dose groups (by 182% and 78.5%, respectively) compared to those of pure CRD. The greater oral AUC of CRD for DA-9701 than for pure CRD could be due to decreased hepatic and/or GI first-pass extraction of CRD by other components in DA-9701.     

Absorptive profile of chlorogenic acid in rats

The objective of this work was to systematically investigate the absorptive profile of chlorogenic acid (CGA) in rats and to increase its intestinal absorption using absorption enhancers. The rat in situ intestinal perfusion technique was used to examine absorptive rate and extent of CGA. In vitro enzymatic drug degradation study was carried out with rat intestinal washings. Various experimental conditions such as different concentrations, extraction purity, and different absorption enhancers such as sodium taurocholate (ST), sodium lauryl sulphate (SLS), carbomer, borneol were examined. Absorption rate constants were determined by the plot of log remaining amount of drug in perfusate vs. time. During the in vitro enzymatic degradation study, no measurable degradation was observed. It was found that CGA could be poorly absorbed by the gastrointestinal tract. The absorptive rate of CGA is independent of the drug concentration. Absorption processes fit first order processes. Extraction of high purity is benefit to the absorption of CGA. Drug absorption extent could be increased via absorption enhancers except SLS. ST appeared to be more effective for enhancing the intestinal absorption of CGA than the other absorption enhancers. In vivo studies were carried out to compare the pharmacokinetic parameters of solutions with and without ST. The order of increasing CGA absorption caused by the enhancers was ST > carbomer > borneol > SLS.     

鉴定大鼠注射绿原酸后体内的代谢产物

绿原酸为多种中药注射液的主要成分, 本文采用超高效液相色谱-四极杆飞行时间质谱法 (UPLC/Q- TOF MS) 鉴定大鼠注射给予绿原酸后胆汁、尿、粪和血浆中的代谢产物。利用碰撞能量梯度 (MS^E) 和质量亏损过滤 (MDF) 技术, 在大鼠胆汁、尿、粪和血浆中共检测到35种代谢产物。胆汁中主要代谢产物为O-甲基绿原酸谷胱甘肽结合物, 其排泄量超过胆汁中全部代谢物的80%, 尿中主要为原形、O-甲基结合物、水解代谢产物及葡糖醛酸结合物, 粪中主要为O-甲基结合物及其半胱氨酸结合物, 血浆中主要为原形化合物。绿原酸及其代谢产物经尿和粪便排泄比例相近。实验结果表明, 绿原酸在大鼠体内代谢广泛, 主要途径之一是与谷胱甘肽结合, 提示绿原酸的烯酮双键具有亲电性, 可能与蛋白的巯基共价结合, 导致过敏性不良反应, 应予以关注。