七叶皂苷钠对博莱霉素致大鼠肺纤维化的干预作用的研究

目的探讨七叶皂苷钠对实验性大鼠肺纤维化的保护作用。方法 50只清洁级Wistar雄性大鼠采用数字随机法分为空白对照组、盐水对照组、模型组和治疗组。模型组和治疗组采用博莱霉素诱导大鼠肺纤维化模型。治疗组造模后第2天起给予七叶皂苷钠5mg/kg腹腔注射,连续7d。造模后第7、14、28天随机处死大鼠,留取肺组织,检测各组大鼠肺组织中转化生长因子(TGF)-β1表达的变化。结果模型组大鼠肺组织中TGF-β1表达量高于空白对照组、盐水对照组及治疗组,第28天与治疗组比较差异无统计学意义(P>0.05),余各时间点与空白对照组、盐水对照组及治疗组比较差异均有统计学意义(P<0.01,P<0.05)。结论七叶皂苷钠能明显抑制博莱霉素致肺纤维化大鼠早期肺组织TGF-β1的过高表达。     

探讨依达拉奉联合七叶皂苷钠治疗脑出血的疗效观察

目的对依达拉奉联合七叶皂苷钠治疗脑出血的效果进行观察与探讨。方法将100例脑出血患者分为观察组(依达拉奉联合七叶皂苷钠治疗)与对照组(七叶皂苷钠单独治疗),比较两组患者用药前后的血肿体积。结果两组的血肿体积明显缩小,观察组变化更明显。结论依达拉奉与七叶皂苷钠联合治疗脑出血的疗效,远远优于单纯使用七叶皂苷钠。     

七叶皂苷钠对油酸制备大鼠急性肺损伤模型的干预研究

目的探讨七叶皂苷钠对油酸诱导大鼠急性肺损伤模型的干预作用。方法♂SD大鼠54只随机分为5组,分别为正常对照组、注射七叶(非油酸造模)组、油酸造模组、甲基强的松龙组和七叶皂苷钠组。采用鼠尾静脉缓慢注射油酸(OA,0.1ml.kg-1)复制大鼠急性肺损伤模型,模型复制成功后按相应措施处理观察并取血取材检测相关指标。观察检测指标有肺组织形态学、肺湿/干重(W/D)、光镜下半定量肺损伤评分(IQA)、血气分析动脉血氧分压(PaO2)、血浆及肺组织匀浆超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量。结果①肺组织形态学:七叶皂苷钠组及甲基强的松龙组肺表面充血程度较油酸组明显减轻,气管内粉红色分泌物溢出减少;光镜下,七叶皂苷钠组及甲基强的松龙组较油酸造模组肺泡腔内炎症细胞渗出减轻;②肺湿/干重(W/D):油酸造模组W/D较空白对照组明显升高,七叶皂苷钠组及甲基强的松龙组W/D较油酸造模组明显降低;③光镜下半定量肺损伤评分(IQA):油酸造模组IQA较空白对照组明显升高,七叶皂苷钠组及甲基强的松龙组IQA较油酸造模组明显降低;④血气分析动脉血氧分压(PaO2):油酸造模组PaO2较空白对照组明显降低,七叶皂苷钠组及甲基强的松龙组PaO2较油酸造模组升高;⑤血浆及肺组织匀浆超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量:油酸造模组血浆及肺组织SOD活性较空白对照组明显降低,七叶皂苷钠组及甲基强的松龙组血浆和肺组织SOD活性较油酸造模组明显升高;油酸造模组血浆及肺组织MDA含量较空白对照组明显升高,七叶皂苷钠组及甲基强的松龙组血浆和肺组织MDA含量较油酸造模组明显降低。结论七叶皂苷钠通过对急性肺损伤大鼠氧化应急的调节作用,以改善W/D、IQA、PaO2,从而为临床治疗急性肺损伤提供一个可能的途径。     

β-七叶皂苷钠在脑缺血再灌注大鼠体内药代动力学的研究

目的:研究β-七叶皂苷钠在脑缺血再灌注大鼠体内的药代动力学规律。方法:应用酶联免疫吸附分析(ELISA,enzyme-linked immunosorbent assay)检测方法,测定正常大鼠及脑缺血大鼠经静脉注射β-七叶皂苷钠5 mg.kg-1后β-七叶皂苷钠的血药浓度,并对其药物代谢动力学参数进行研究。结果:脑缺血再灌注及正常大鼠静脉注射β-七叶皂苷钠5mg.kg-1后,其药代动力学模型符合二室模型。正常大鼠在静脉注射β-七叶皂苷钠后,血药浓度迅速下降,大约20 min后,其血浆药物浓度已下降50%,T1/2α=0.343 h,T1/2β=23.325 h。约2 h后,血浆药物浓度下降速率减慢。而脑缺血再灌注大鼠脑缺血30 min后,静脉注射β-七叶皂苷钠后,其体内药物代谢规律与正常大鼠不同,药物的代谢速率减慢,且在3 h出现一个较低的血药浓度峰,随后血浓下降。结论:β-七叶皂苷钠在脑缺血再灌注大鼠体内的消除较正常大鼠慢,在体内停留的时间较长。提示β-七叶皂苷钠在临床的对症治疗时应考虑其药代动力学的特点。     

紫苏配伍组方对高脂血症模型大鼠的调脂作用

目的研究紫苏配伍组方对高脂血症模型大鼠的调脂作用。方法采用高脂饲料喂养建立高脂血症大鼠模型，根据总胆固醇（TC）水平将大鼠随机分为7组：正常对照组、模型对照组、降脂灵片组、洛伐他汀组和紫苏配伍组方低、中、高剂量组。连续灌胃给药30 d，分别于给药第15天和末次给药后检测TC、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL C）、高密度脂蛋白胆固醇（HDL C）含量。结果与模型组比较，紫苏配伍组方低、中、高剂量组和洛伐他汀组给药15 d后大鼠血清TC含量均显著降低；紫苏配伍组方低、中、高剂量组大鼠血清LDL C含量均显著降低。末次给药后紫苏配伍组方低、中、高剂量组，降脂灵组和洛伐他汀组与模型组比较大鼠血清TC含量均显著降低；紫苏配伍组方中、高剂量组与降脂灵组、洛伐他汀组大鼠血清LDL C含量均显著降低；紫苏配伍组方各剂量组、洛伐他汀组和降脂灵片组大鼠血清TG变化不明显；紫苏配伍组方中剂量组大鼠血清HDL C/ LDL C比值显著提高。结论紫苏配伍组方具有显著调脂作用。     

洛伐他汀联合阿昔莫司治疗高脂血症的疗效

目的:观察洛伐他汀联合阿昔莫司治疗混合型高脂血症的疗效与安全性.方法:60例门诊确诊为高脂血症患者随机分两组,一组单药组(洛伐他汀20 mg,po,qn),一组联合用药(洛伐他汀20 mg,po,qn 阿昔莫司0.25 g,po,bid).每组30人,两组均连续治疗3个月,比较两组治疗前后血脂变化,并记录不良反应.结果:2组患者总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)水平均显著降低;但联合治疗组TC、TG、LDL-C降低水平明显优于单药组(P＜0.05).联合治疗组除皮肤反应高于单药组外,两组不良反应无明显差异.结论:洛伐他汀联合阿昔莫司治疗混合型高脂血症的疗效好,并且安全.     

卡维地洛对那格列奈在大鼠体内药物动力学的影响

目的研究卡维地洛对那格列奈在大鼠体内药物动力学的影响。方法 10只健康雄性Wistar大鼠随机分成2组(单独给药组和联合给药组),用HPLC-MS/MS法测定血浆中那格列奈的浓度。结果单独用药与联合用药组Cmax分别为(1 868±226.3)和(992.8±246.0)μg.L-1,AUC0-t分别为(1 532.1±526.5)和(822.5±298.0)μg.h.L-1,AUC0-∞分别为(1 546.2±530.7)和(845.1±312.0)μg.h.L-1,均具有显著性差异(P<0.05),其他药动学参数无显著性差异(P>0.05)。结论联合用药后卡维地洛抑制了那格列奈的吸收。     

β-七叶皂苷钠在家兔体内的药动学研究

目的:建立家兔血液中七叶皂苷钠的测定方法。方法:应用酶联免疫吸附分析(ELISA)方法,测定正常家兔与脑缺血再灌注模型家兔静脉注射β-七叶皂苷钠(5mg/kg)后的血药浓度,并对其药动学参数进行分析。结果:正常家兔与模型家兔静脉注射β-七叶皂苷钠后,主要药动学参数t1/2α分别为(0.343±0.061)、(0.854±0.079)h,t1/2β分别为(23.325±10.36)、(34.283±13.74)h,CL分别为(1.600±1.206)、(0.718±0.428)L/h,Vd分别为(53.827±36.42)、(14.799±10.15)L,AUC0-24h分别为(2.919±0.981)、(26.417±9.207)μg(/h.L),AUC0-∞分别为(3.126±1.253)、(27.848±8.745)μg(/h.L),cmax分别为(4.126±0.927)、(7.905±1.054)mg/L。结论:β-七叶皂苷钠在脑缺血再灌注模型大鼠体内的消除较正常大鼠慢,在体内停留的时间较长。提示β-七叶皂苷钠在临床对症治疗时应考虑其药动学特点。     

洛伐他汀联合异烟肼、利福平、吡嗪酰胺致大鼠肝损伤的实验研究

目的 探讨洛伐他汀联合异烟肼(H)、利福平(R)、吡嗪酰胺(Z)(联用简称为HRZ)致大鼠肝损伤的特点.方法 SPF级8周龄SD大鼠80只,雌雄各半,采用随机数字表法随机分为四组:空白对照组、洛伐他汀组、HRZ组、洛伐他汀+HRZ组,按人-鼠间药物剂量换算,分别给予相应药物灌胃,于10、35、55 d分别处死大鼠,采集标本行肝功能生化指标、肝病理学检测及电镜观察.结果 在给药10、35、55 d时,与空白对照组比较,洛伐他汀+HRZ组肝功能生化指标均明显升高,总胆红素(TBil)、直接胆红素(DBil)、间接胆红素(IBil)升高,差异有统计学意义,而天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、碱性磷酸酶(ALP)升高,差异无统计学意义,且随着给药时间点延长,洛伐他汀+HRZ组肝损伤并未呈进行性增加;与洛伐他汀组、HRZ组两两比较时,仅AST在给药55 d时洛伐他汀组与HRZ组比较差异有统计学意义,其他各组在各时间点两两比较均差异无统计学意义;以上结果与病理、电镜观察结果一致.结论 洛伐他汀联合HRZ后短时间内即可能出现肝损伤,以胆汁淤积型肝损伤为主;且随着给药时间延长,洛伐他汀联合HRZ所致肝损伤可能存在适应性现象,联合组并未比洛伐他汀单用或HRZ单用更容易导致肝损伤.     

双氯芬酸钠贴剂绝对生物利用度和局部组织药物浓度研究

目的: 研究兔经皮给予双氯芬酸钠贴剂的绝对生物利用度和局部组织药物浓度,为临床合理用药提供参考.方法: 单剂量给予静脉给药和贴剂,采用反相HPLC测定血浆和局部组织中双氯芬酸钠的浓度.结果: 兔表皮给予双氯芬酸钠贴剂的药代动力学参数为:AUC22.63(μg·h·ml-1),t1/2Ka0.82 h, t1/2Ke8.51 h, tmax2.53 h, Cmax1.64(μg·ml-1), CL0.91(L·h-1), Ka1.15(h-1), Ke0.12(h-1);静脉给药在兔体内的药代动力学参数为AUC 43.85(μg·h·ml-1),t1/2Ke0.60 h, Cmax51.17(μg·ml-1),CL0.47(L·h-1), Ke1.16(h-1).求算得双氯芬酸钠贴剂的绝对生物利用度为51.6%,对两种制剂的药代动力学参数进行双单侧t检验,均有显著性差异(P<0.05).再对给予贴剂的兔皮肤、肌肉、血浆3组之间进行LSD检验,各组间均有显著性差异(P<0.05),皮肤中的药物浓度是血浆的36.5倍.结论: 双氯芬酸钠贴剂的Cmax、AUC低于静脉给药,但具有达峰时间长和在体内时间长的特点,具有长效作用.贴剂的血药浓度较低,而局部血药浓度高,避免了双氯芬酸钠所形成的不良反应.     

Effect of roxithromycin on the pharmacokinetics of lovastatin in volunteers

OBJECTIVE: To investigate the influence of concomitant administration of roxithromycin on the plasma pharmacokinetics of lovastatin. METHODS: In an open, randomized, crossover study, 12 healthy volunteers received 80 mg lovastatin orally either alone or concomitantly with 300 mg roxithromycin after 5-day pretreatment with roxithromycin 300 mg daily. Plasma concentrations of lovastatin (lactone and acid) were determined using high-performance liquid chromatography, and the pharmacokinetic parameters were estimated. RESULTS: The mean (+/- SD) pharmacokinetic parameters of lovastatin lactone with and without roxithromycin were maximum concentration (Cmax) 8.49+/-6.80/16.3+/-9.4 ng ml(-1), time to Cmax (tmax) 1.8+/-0.4/1.7+/-0.6 h, terminal plasma half-life (t1/2) 4.3+/-2.0/3.7+/-2.5 h, area under the plasma concentration-time curve from zero to infinity (AUC0-infinity) 53+/-60/85+/-67 ng ml(-1) h. The respective parameters of lovastatin acid were Cmax 24.6+/-13.4/17.8+/-11.0 ng ml(-1), tmax 3.7+/-1.1/4.1+/-0.7 h, t1/2 3.2+/-2.5/4.3+/-2.8 h, AUC0-infinity 149+/-123/105+/-58 ng ml(-1) h. Mean bioavailability of lovastatin lactone was lower and that of lovastatin acid was higher with concomitant treatment. However, the differences were significant only with respect to lovastatin lactone (AUC and Cmax) and Cmax of lovastatin acid. CONCLUSION: Roxithromycin does not influence the pharmacokinetics of lovastatin in such a way that dosage adjustment of lovastatin seems to be necessary during co-administration.     

洛伐他汀联御旨必妥治疗高脂血症的临床应用价值

目的探讨洛伐他汀联合脂必妥治疗高脂血症的临床价值。方法将我中心2012年1月～2013年5月收治的高脂血症患者168例按不同治疗方法分为实验组（洛伐他汀＋脂必妥）和对照组（洛伐他汀）,均治疗8周后对两组患者的治疗效果进行综合比较。结果实验组总有效率为90．47％,明显优于对照组的75．00％（P〈0．05）,实验组的总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL—C）、TC—HDL—C／HDL—C均较对照组明显降低（P〈0．05）,高密度脂蛋白胆固醇（HDL—C）较对照组明显升高（P〈0．05）。结论洛伐他汀联合脂必妥治疗高脂血症的临床效果显著,且有较高安全性,值得临床推广应用。     

The effect of increased lipoprotein levels on the pharmacokinetics of cyclosporine A in the laboratory rat

The response of cyclosporine A (CyA) blood concentrations following changes in lipoprotein levels have been inconsistent. Some studies show increases in concentrations, whereas others have shown decreases. The intent of this study was to examine the effect of two rat models of increased lipoprotein on the pharmacokinetics of CyA. One was a simulated high fat content meal, in which 1% cholesterol in peanut oil was administered. The other was the poloxamer 407-induced model of hyperlipidemia. Rats in these two groups were compared to a group fasted overnight before the study. In rats given a simulated high fat meal, at most time points the mean blood and plasma concentrations were lower, though not significantly, compared to fasted animals. Oral lipid led to no significant changes in the measured pharmacokinetic parameters of blood or plasma area under the concentration vs time curve (AUC), clearance (CL), volume of distribution (Vd) or plasma unbound fraction. In the poloxamer 407-treated hyperlipidemic rats there were significant reductions in plasma unbound fraction plasma, Vd and terminal half-life, but not AUC or CL, compared to normolipidemic rats. In contrast, the CL, Vd and t1/2 in the oral lipid-fed rats were all significantly higher than the poloxamer 407 treated animals. Oral absolute bioavailability of CyA was unchanged by oral lipid. In humans and rats the pharmacokinetics of CyA in the face of increased lipoprotein levels do not correspond well to what is typically seen for other drugs that are known to bind to lipoproteins.     

甘草酸对水飞蓟宾在大鼠体内药代动力学的影响

目的研究甘草酸对水飞蓟宾在大鼠体内药代动力学的影响。方法对大鼠分别灌胃水飞蓟宾(SLB)-甘草酸(GL)混悬液和水飞蓟宾(SLB)混悬液,采用高效液相色谱法测定大鼠血浆中水飞蓟宾浓度。用DAS 2.0软件处理数据,计算两组的药代动力学参数。结果SLB-GL混悬液组和SLB混悬液组的药代动力学参数Cmax分别为1.91μg·mL^-1和0.43μg·mL^-1,AUC(0→t)分别为5.45μg·mL^-1·h和1.91μg·mL^-1·h。与SLB混悬液组对比,SLB-GL混悬液组Cmax和AUC(0→t)分别增加344.19%和185.34%(P<0.05)。结论甘草酸可影响水飞蓟宾在大鼠体内的药代动力学过程,使得水飞蓟宾在大鼠体内的血药浓度和生物利用度升高。     

艾拉莫德在大鼠体内的药动学研究

目的 研究艾拉莫德在正常与佐剂性关节炎大鼠体内的药动学行为.方法 用高效液相色谱法测定血清中艾拉莫德的浓度,并计算其药动学参数.结果 连续给药后正常组(6 mg/kg)的主要药动学参数为:t1/2Ke:6.30 h;tpcak:4.00 h;Cmax:8.87 μg/ml;AUC0.24:98.52 μg·ml-1.连续给药后,关节炎大鼠低、中、高三个剂量组(3、6、12 mg/kg)的主要药动学参数分别为:t1/2Ke:6.03、6.24、6.89 h;tpcak:3.83、3.83、4.67 h;Cmax:3.84、8.31、12.69μg/ml;AUC0.24:48.67、91.02、145.10μg·ml-1·h-1.经检验,除Cmax和AUC外,关节炎大鼠三个剂量组的药动学参数之间差异无统计学意义,Cmax和AUC值与剂量成正比.正常与关节炎大鼠的药动学参数比较,差异无统计学意义.结论 艾拉莫德在正常和佐剂性关节炎大鼠体内的药动学行为符合开放型一室模型一级速率过程.     

Effects of poloxamer 407-induced hyperlipidemia on the pharmacokinetics of carbamazepine and its 10,11-epoxide metabolite in rats: Impact of decreased expression of both CYP3A1/2 and microsomal epoxide hydrolase

The pharmacokinetics of carbamazepine (CBZ) and its active 10,11-epoxide metabolite (CBZ-E) were evaluated after intravenous and oral administration of 5 mg/kg CBZ to rats with hyperlipidemia induced by poloxamer 407 (HL rats) and controls. The total area under the plasma concentration-time curve (AUC) of CBZ in HL rats after intravenous administration was significantly greater than that in controls due to their slower non-renal clearance (CL(NR)). This was due to slower hepatic CL(int) for metabolism of CBZ to CBZ-E in HL rats via CYP3A1/2. This result was consistent with a previous study indicating reduced hepatic CYP3A1/2 expression in HL rats. Interestingly, the AUC of CBZ-E was also increased in HL rats, while AUC(CBZ-E)/AUC(CBZ) ratios remained unchanged. These results suggested that further metabolism of CBZ-E to the inactive metabolite trans-10,11-dihydoxyl-10,11-dihydro-CBZ (CBZ-D) via microsomal epoxide hydrolase (mEH) was also slowed in HL rats. The significantly reduced hepatic mRNA level and expression of mEH protein in HL rats compared to controls confirmed the above hypothesis. Similar pharmacokinetic changes were observed in HL rats after oral administration of CBZ. These findings have potential therapeutic implications assuming that the HL rat model qualitatively reflects similar changes in patients with hyperlipidemia. Caution is required regarding pharmacotherapy in the hyperlipidemic state in cases where drugs that are metabolized principally by CYP3A1/2 or mEH and have a narrow therapeutic range are in use.     

Effects of bile salts on the lovastatin pharmacokinetics following oral administration to rats

This study aimed to examine the effects of bile salts on pharmacokinetics of lovastatin, which has low bioavailability. Lovastatin solid dispersions were prepared using sodium deoxycholate (NaDC) and sodium glycholate (NaGC) at ratios of 1:19, 1:49, and 1:69. The formulated solid dispersions and control (commercial tablet) were administered to rats and plasma concentrations were determined by a validated LC-MS/MS method. Statistically significant differences were found in C_max, AUC_0–10, and AUC_0–∞ values among lovastatin formulations (p?<?0.05). NaDC-containing formulations revealed higher bioavailabilities than NaGC-containing solid dispersions at ratios of 1:19 and 1:49. Especially, NaDC-containing formulation at a ratio of 1:19 (NaDC19) showed the highest bioavailability. The AUC (both AUC_0–10 and AUC_0–∞) of NaDC19 was statistically higher than control and NaDC69 (p?<?0.05). The AUC values decreased as bile salt concentrations increased. Overall, formulations containing bile salts showed higher AUC values than control, even though all formulations did not show significantly higher AUC. In conclusion, the addition of bile salts to lovastatin could enhance drug bioavailabilities. However, too high concentrations of bile salts could decrease bioavailabilities of lovastatin.     

沙利度胺对伊立替康及其代谢物SN-38在大鼠体内药动学的影响

目的:研究伊立替康合用沙利度胺后伊立替康及其代谢物SN-38在大鼠体内的药动学情况。方法:以健康♂SD大鼠为受试对象,随机分成伊立替康注射液10、20mg·kg-1单用组(对照组)及与沙利度胺(20mg·kg-1)合用组(实验组),给药后0.083、0.5、1.0、2.0、4.0、6.0、8.0、10、12h采集血样并测定伊立替康、SN-38血药浓度,采用DASver2.0软件拟合二者的药动学参数。结果:与对照组比较,伊立替康10mg·kg-1实验组伊立替康AUC0～t、Cmax显著增加(P<0.05),SN-38的AUC0～t降低(P<0.05);20mg·kg-1实验组伊立替康Cmax显著增加(P<0.05),SN-38的Cmax、AUC0～t显著降低(P<0.05)。结论:联用沙利度胺可以增加伊立替康AUC0～t同时减少SN-38的AUC0～t及Cmax。