功劳去火片中黄芩苷和小檗碱在大鼠体内的药物动力学

目的 建立同时测定大鼠体内黄芩苷和小檗碱血药浓度的方法,用于研究功劳去火片中两种指标成分的药物动力学.方法 给予大鼠ig功劳去火片制得混悬液,给药前及给药后不同时间采集血样,采用HPLC法测定血样中的黄芩苷和小檗碱,药-时数据经3p97软件分析处理,并与文献比较,判断给药形式的影响.结果 黄芩苷和小檗碱的线性范围分别为0.061～3.910、0.017～1.060 μg·ml-1,最低定量限分别为0.061、0.017 μg·ml-1.两者的平均回收率均大于97.2%,精密度与准确度均符合生物样品分析要求.给药后,黄芩苷在大鼠体内的代谢符合二室模型,主要药动学参数为:K21=0.74±0·301/h,K10 0=0.143±o.035 1/h,K12=1.26±0.80 1/h,t1/2β=13.5±1.0 h,t1/2α=0.40±0.18 h,Tmax=0.352±0.086 h,Cmax=0.944±0.18μg·ml-1.小檗碱符合一室模型,其主要药动学参数为:t1/2(Km)=3.65 ±0.96 h,t1/2(Ka)=0.073±0.019 h,1/2(Km)=0.1076±0.022 h,Tmax=0.60±0.12 h,Cmax0.254±059 μg·ml-1.结论 功劳去火片中黄芩苷和小檗碱的药物动力学受中药复方给药形式的影响,与单指标成份给药有差异.     

解热药YL2000中小檗碱在正常和发热大鼠体内的药物动力学比较

目的　探讨解热药YL2 0 0 0中小檗碱在正常和发热大鼠体内的药物动力学。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小檗碱的含量 ,使用3P87软件处理小檗碱的时量数据 ,计算各药代动力学参数。结果　在正常和发热大鼠体内 ,小檗碱的达峰时间分别为(3 4± 0 3)h和 (0 3± 2 1)h(P <0 0 5 ) ,峰值血药浓度分别达 (0 15 4± 0 0 2 3)mg·L-1和 (0 2± 0 6 )mg·L-1,T1/ 2(ke)分别长达 (6± 3)h和 (6± 5 )h ,T1/ 2 (ka)分别为 (1 2±0 4 )h和 (0 1± 2 8)h ,CL/F(s)值分别为 (4 0± 1 9)mg·kg-1·h-1/ (mg·L-1)和 (6± 6 )mg·kg-1·h-1/ (mg·L-1) ,AUC( 0～T) 值分别为 (1 8± 0 3)mg·L-1·h-1和 (0 7± 0 5 )mg·L-1·h-1(P <0 0 5 )。结论　发热降低小檗碱在体内的AUC( 0～T) 。     

黄芩汤中黄芩苷大鼠药代动力学特征研究

目的:通过大鼠药代动力学实验,测定大鼠灌胃黄芩汤后血浆中黄芩苷的含量,研究其药代动力学特征。方法:建立大鼠药代动力学模型,于24 h内不同时间点采集血浆样品,HPLC测定血浆中黄芩苷浓度,绘制药时曲线并运用DAS2.0软件进行数据处理。结果:黄芩汤中的黄芩苷主要药动学参数:Tmax=(0.5±0.015)h、Cmax=(3.868±0.135)mg﹒L~(-1)、t_(1/2z)=(2.626±0.09)h、CLz/F=(8.604±0.696)L﹒h~(-1)﹒kg~(-1);结论:黄芩苷在大鼠体内药时曲线呈现双峰特征,有良好的药代动力学特征。     

小檗碱对大鼠口服阿托伐他汀钙药代动力学的影响

目的研究小檗碱对大鼠口服阿托伐他汀钙药代动力学的影响,为临床联合用药提供参考依据。方法大鼠随机分为5组,单次阿托伐他汀钙组(A组)、单次小剂量小檗碱+阿托伐他汀钙组(B组)、单次大剂量小檗碱+阿托伐他汀钙组(C组)、多次小剂量小檗碱+单次阿托伐他汀钙组(D组)及多次大剂量小檗碱+单次阿托伐他汀钙组(E组)。给药前后眼眶采血,采用HPLC法测定大鼠体内阿托伐他汀钙的浓度。经DAS 2.0药动学软件处理,获得各组药动学参数。结果大鼠在单次及多次灌胃不同剂量的小檗碱后,阿托伐他汀钙的体内药代动力学参数改变无统计学意义。结论正常用量下小檗碱对大鼠阿托伐他汀钙的药代动力学有一定的影响,但无统计学意义,在人体内的影响仍需进一步研究。     

黄芩苷及其含药血清在大鼠体内的药动学、药效学相关性研究

目的:以黄芩苷含药血清对PC12细胞氧化损伤的保护作用为药效指标,研究黄芩苷的体内药动学及药效学过程的相关性。方法:大鼠灌胃后,测定不同取血点血清样本中的黄芩苷含量,运用血清药理学方法,观察血清样本对H2O2诱导PC12细胞氧化损伤模型的保护作用,对浓度-时间、效应-时间曲线进行相关分析,建立药动-药效结合模型;观察不同浓度黄芩苷溶液的保护作用,获得黄芩苷体外抗氧化作用的量效关系。结果:黄芩苷含药血清对PC12细胞氧化损伤有明显保护作用,且具有时间依赖性。效应-时间曲线的Emax为98%,tmax为15min;浓度-时间曲线的Cmax为9.39μg.ml-1,tmax亦为15min,以Log(AUC)-AUE作图,图形近似呈“S”形。体外实验中,黄芩苷浓度在0.16~10μg.ml-1范围内有抑制作用,且作用随剂量增加而增大。结论:黄芩苷体内、外均具有抗氧化作用,且效应的时效关系与血清中黄芩苷的时量关系呈正相关。     

聚乙二醇400对黄芩苷在大鼠体内药动学的影响

目的 考察聚乙二醇400 (PEG400)对黄芩苷在大鼠体内药动学的影响.方法 将大鼠随机分为黄芩苷组和PEG400组,黄芩苷组大鼠单独灌胃给予黄芩苷,PEG400组的灌胃给予黄芩苷和PEG400混合物,于不同时间点取静脉血,用HPLC法检测血浆中的黄芩苷,绘制药时曲线,用DAS 2.0计算药动学参数.结果 黄芩苷的线性范围为0.3203 ～ 10.25 μg·mL-1,定量下限为0.3203 μg· mL-1,日内、日间RSD均＜10％,提取回收率＞85％,PEG400组的AUC0-t明显高于黄芩苷组.结论 PEG400可促进黄芩苷在大鼠体内的吸收.     

左金丸配伍意义的药物代谢动力学分析

目的研究左金丸在SD大鼠体内的药代动力学,为临床应用提供参考。方法将左金丸及黄连、吴茱萸制成水煎液,对SD大鼠进行灌胃,HPLC法测定并计算小檗碱、吴茱萸次碱的药代动力学参数。结果左金丸组的小檗碱的t1/2延长,tmax缩短,Cmax增大,AUC（0-∞）增加,代谢较缓慢;吴茱萸次碱tmax缩短,Cmax增大,AUC（0-∞）增加。结论左金丸中黄连∶吴茱萸为6∶1时,能很好地发挥作用。     

氨基胍、葛根素、小檗碱、黄芩苷和甘草酸对D-半乳糖诱导大鼠醛糖还原酶活性和蛋白非酶糖化作用的比较

目的观察氨基胍、葛根素、小檗碱、黄芩苷和甘草酸对D-半乳糖(D-gal)诱导大鼠体内醛糖还原酶(AR)活性、糖耐量和蛋白非酶糖基化反应的作用。方法除空白对照组外,其余大鼠均采用腹腔注射(ip)D-gal 150mg? kg-1,qd×56d致病,D-gal处理大鼠2周后,将大鼠按体重均衡随机分成:模型对照、氨基胍、葛根素、小檗碱、黄芩苷和甘草酸5组,然后继续ip D-gal处理同时灌胃给予不同药物(300mg?kg-1?10ml-1)或蒸馏水,qd×42d;实验结束时,观察5药对D-半乳糖诱导大鼠体内醛糖还原酶(AR)活性、糖耐量和蛋白非酶糖基化反应的作用。结果与空白对照组比较,D-gal处理大鼠出现糖耐量减退(IGT)、糖基化产物(包括糖化血红蛋白即HbA1c、果糖胺和晚期糖基化终产物)增高以及红细胞内AR活性增强(P<0．01);氨基胍、葛根素、小檗碱、黄芩苷与甘草酸均能明显抑制AR活性(P<0．01-0．05);氨基胍、葛根素、小檗碱和黄芩苷均能改善D-gal诱导大鼠IGT(P<0．01-<0．05);氨基胍、葛根素和小檗碱能降低糖基化产物的含量(P<0．01-0．05),而黄芩苷仅降低HbA1c含量(P<0．05);甘草酸对糖基化产物含量未见明显影响(P>0．05)。结论氨基胍、葛根素、小檗碱、黄芩苷和甘草酸均能抑制D- gal诱导大鼠体内醛糖还原酶活性,氨基胍、葛根素与小檗碱对D-gal诱致的大鼠糖基化反应具有明显的抑制作用,而黄芩苷对大鼠糖基化反应具有部分抑制作用,甘草酸对大鼠糖基化反应未见抑制作用。     

白藜芦醇苷的HPLC法分析及其在苗猪体内的药代动力学研究

目的 :建立血浆中白藜芦醇苷的反相高效液相色谱分析方法 ,并对其在苗猪体内的药代动力学进行研究。方法 :采用HypersilODS色谱柱 (10 0mm× 2 1mm ,5 μm) ,甲醇 -水 (2 5∶75 )为流动相 ,流速 1 0mL·min-1,检测波长 2 90nm。结果 :方法平均回收率为 93 3 %～ 98 1% ,RSD <6 0 % ,线性范围 0 39～ 12 5 0mg·L-1(r =0 9947) ,最低检测浓度为 0 2 0mg·L-1。结论 :本试验首次建立了白藜芦醇苷血药浓度的HPLC测定方法 ,操作方便 ,结果准确 ,可用于该药的进一步临床药动学研究     

黄芩苷与盐酸小檗碱在大鼠小肠吸收的相互作用研究

目的:研究黄芩苷与盐酸小檗碱在大鼠小肠吸收的相互作用。方法:采用大鼠原位灌注模型研究药物配伍前、后大鼠小肠吸收动力学特征。结果:黄芩苷在配伍盐酸小檗碱前、后,其吸收速率常数(ka)与吸收率(A)分别为(0.068±0.002)h-1、(5.92±1.39)%和(0.060±0.002)h-1、(4.27±1.23)%;盐酸小檗碱在配伍黄芩苷前、后,其ka和A分别为(0.044±0.003)h-1、(3.47±0.64)%和(0.057±0.006)h-1、(5.18±0.83)%。药物配伍前、后,黄芩苷的ka有显著性差异(P<0.05),盐酸小檗碱的ka和A均有显著性差异(P<0.05)。结论:盐酸小檗碱可以抑制黄芩苷的吸收,黄芩苷可以促进盐酸小檗碱的吸收。     

Pharmacokinetic/pharmacodynamic relationship of eptazocine, a narcotic-antagonist analgesic, in rats

The relationship between the pharmacokinetics and the pharmacodynamics of eptazocine, a narcotic-antagonist analgesic, was investigated in rats. The analgesic effect of eptazocine (2.5, 5 and 10 mg/kg) following intravenous (i.v) administration was evaluated by both the Randall-Selitto method and the D'Amour-Smith method. The analgesic effects were determined before and at designed intervals for a period of 120 min after eptazocine administration, and are expressed as area under the effect-time curve (AUC(E)). The plasma concentration of eptazocine was determined by fluorescence HPLC and was analyzed with a two compartment open model using the nonlinear least-squares method. Eptazocine produced a dose-dependent analgesic effect. It was demonstrated that eptazocine has a linear relationship between AUC(E) and the area under the plasma concentration-time curve (AUC) following i.v. administration for three different doses ranging from 2.5 to 10 mg/kg.     

头孢呋辛钠与头孢呋辛钠复方制剂在Beagle犬体内的药动学考察

目的研究头孢呋辛钠舒巴坦钠复方制剂中头孢呋辛在Beagle犬体内的药动学行为,并比较单组分头孢呋辛与复方制剂中头孢呋辛的药动学差异。方法采用高效液相色谱法(HPLC)测定Beagle犬静脉给予头孢呋辛钠复方制剂不同剂量和单独给予头孢呋辛钠后不同时刻血浆中头孢呋辛的浓度,计算主要药动学参数。结果犬静脉给予头孢呋辛钠复方制剂(等同于头孢呋辛57.0、142.6和356.5 mg.kg-1)3个剂量后,头孢呋辛的t1/2分别为(1.1±0.2)、(1.0±0.1)和(1.2±0.3)h;ke分别为(0.693±0.119)、(0.707±0.094)和(0.591±0.117)h-1;犬静脉给予头孢呋辛钠(等同于头孢呋辛57.0 mg.kg-1)后,头孢呋辛的t1/2和ke分别为(1.2±0.3)h和(0.615±0.133)h-1。结论 Beagle犬静脉给予头孢呋辛钠复方制剂低、中、高3种剂量后,头孢呋辛呈线性动力学特征,且复方制剂与单一制剂中头孢呋辛的药动学行为无显著差异。     

Evaluation of pharmacokinetic and pharmacodynamic relationship for oral sustained-release atenolol pellets in rats

This study was designed to evaluate the in vitro release, pharmacokinetics (PK), pharmacodynamics (PD) and PK-PD relationships of atenolol sustained-release pellets (AT-SRPs), compared with those of atenolol immediate-release pellets (AT-IRPs). Blood sampling for AT plasma concentration was performed in normal rats and blood pressure-lowering effects were recorded continuously in hypertensive rats (HRs) before and at 1, 4, 8, 12, 16 and 24 h after drug administration. The parameters were calculated using DAS1.0 program and WinNonlin software. The release profile of SRPs was steadier and more sustained than that of IRPs. The mean Cmax and area under concentration-time curve from 0 to 24 h after administration (AUC0-24 h) of SRPs were significantly lower than that of IRPs (p<0.05), while area under concentration-time curve from 0 to infinity (AUC0-∞) was almost equivalent between the two formulations. The mean half life time (t1/2) of AT-SRPs was almost 2 times longer compared to that of AT-IRPs. The SRPs approximately achieved half of peak drug effect (Emax) of IRPs, while there were no significant differences in the area under effect-time curve from 0 to 24 h after administration (AUEC0-24 h) and the area under effect-time curve from 0 to infinity (AUEC0-∞). The value of the rate constant of equilibration between plasma and the effect-site (ke0) for SRPs was about 4 times higher than IRPs. The effect-concentration-time course for AT-SRPs was represented by the clockwise hysteresis loop, while the counter-clockwise hysteresis loop well showed that for AT-IRPs. The more favorable characteristics of SRPs would make it more appropriate as a potential dosage form for the treatment of hypertension.     

Effect of uranyl nitrate-induced renal failure on morphine disposition and antinociceptive response in rats

1. The aims of the present study were to administer morphine (14.0 mumol/kg, s.c.) to male Hooded Wistar rats and to determine the effect of uranyl nitrate-induced renal failure on: (i) the antinociceptive effect of morphine; (ii) the pharmacokinetics of morphine and morphine-3-glucuronide (M3G); and (iii) the relationship between antinociceptive effect and the pharmacokinetics of morphine in plasma and brain. 2. Renal failure was induced by a single s.c. injection of uranyl nitrate and kinetic/dynamic studies were performed 10 days after its administration, when creatinine clearance was 17% of the control group. Antinociceptive effect was measured by the tail-flick method at various times up to 2 h post-drug administration. Concentrations of morphine and M3G in plasma and brain and concentrations of creatinine in urine and serum were determined by specific HPLC methods. 3. After morphine administration, the area under the antinociceptive effect-time curve was decreased by 44% in renal failure rats. There were no differences between control and renal failure rats in: (i) plasma morphine concentration-time curves; (ii) brain morphine concentration-time curves; and (iii) plasma M3G concentration-time curves. Morphine-6-glucuronide was not detected in any plasma or brain sample from rats administered morphine and no M3G was detected in brain. 4. For both control and renal failure rats, the relationships between antinociceptive effect and plasma morphine concentration were characterized by counterclockwise hysteresis loops, probably reflecting a delay for the relatively polar morphine to cross the blood-brain barrier. The relationship between antinociceptive effect and brain morphine concentration in control rats revealed no evidence of acute tolerance and was described by a sigmoidal function. In contrast, the relationship in renal failure rats was characterized by clockwise hysteresis, which is consistent with acute tolerance development.     

盐酸小檗碱、黄芩苷与抗菌药物联用对多重耐药鲍曼不动杆菌作用研究

目的探讨盐酸小檗碱、黄芩苷与6种抗菌药物(头孢他啶、哌拉西林-他唑巴坦、亚胺培南西司他丁钠、氨曲南、左氧氟沙星、加替沙星)对多重耐药鲍曼不动杆菌的联合抑菌作用。方法根据临床药敏结果选取7株鲍曼不动杆菌多重耐药菌株作为实验对象。用微量稀释法测定盐酸小檗碱、黄芩苷分别与6种抗菌药物的联合抑菌效应。结果盐酸小檗碱与亚胺培南西司他丁钠、氨曲南联用表现为协同作用。黄芩苷与氨曲南表现为协同作用。结论盐酸小檗碱、黄芩苷与某些抗菌药物联用后对多重耐药鲍曼不动杆菌的抗菌活性有协同作用,可能对多重耐药鲍曼不动杆菌的治疗有所帮助。     

利巴韦林鱼腥草素钠粉针剂在大鼠体内的药代动力学

目的以利巴韦林单方为参照品 ,测定利巴韦林鱼腥草素钠复方粉针剂中主药成分利巴韦林在大鼠体内的药代动力学 ,并考察粉针剂中另一成分鱼腥草素钠对主药药代动力学的影响。方法采用 5 0 % (φ)高氯酸水溶液沉淀蛋白后正庚烷提取 ,反相高效液相法分别测定了大鼠静脉注射利巴韦林单方药和利巴韦林复方粉针剂后的血药浓度并计算其药代动力学参数。结果利巴韦林复方粉针剂在大鼠体内的隔室模型和药代动力学参数与利巴韦林原料药无显著差别 ,t1/2 β分别为 (2 0 7 5 0 3± 38 6 81)min和 (189 35 4± 2 0 4 80 )min ,AUC分别为 (10 5 8 90 0± 2 5 3 2 78)mg·min·L-1和 (1139 5 12± 383 793)mg·min·L-1。结论利巴韦林鱼腥草素钠粉针剂中的另一成分鱼腥草素钠不影响主药利巴韦林的药代动力学     

First-pass metabolism of decursin, a bioactive compound of Angelica gigas, in rats

Decursin is considered the major bioactive compound of Angelica gigas roots, a popular Oriental herb and dietary supplement. In this study, the pharmacokinetics of decursin and its active metabolite, decursinol, were evaluated after the administration of decursin in rats. The plasma concentration of decursin decreased rapidly, with an initial half-life of 0.05 h. It was not detectable at 1 h after intravenous administration at an area under the plasma concentration-time curve of 1.20 μg · mL-1·h, whereas the concentration of decursinol increased rapidly reaching a maximum concentration of 2.48 μg · mL-1 at the time to maximum plasma concentration of 0.25 h and an area under the plasma concentration-time curve of 5.23 μg · mL-1·h. Interestingly, after oral administration of decursin, only decursinol was present in plasma, suggesting an extensive hepatic first-pass metabolism of decursin. The extremely low bioavailability of decursin after its administration via the hepatic portal vein (the fraction of dose escaping first-pass elimination in the liver, FH = 0.11) is indicative of extensive hepatic first-pass metabolism of decursin, which was confirmed by a tissue distribution study. These findings suggest that decursin is not directly associated with the bioactivity of A.?gigas and that it may work as a type of natural prodrug of decursinol.