单硝酸异山梨酯与阿魏酸在大鼠体内的药动学及相互作用

目的:建立用于同时测定大鼠血浆中单硝酸异山梨酯、阿魏酸的HPLC-UV分析方法,并用于研究单硝酸异山梨酯与阿魏酸在大鼠体内药动学的相互作用。方法:将18只雄性SD大鼠随机分成单硝酸异山梨酯组、阿魏酸钠组以及硝酸异山梨酯和阿魏酸钠联合给药组,于给药后规定时间点采集血样,HPLC-UV法测定二者的血药浓度,采用DAS 2.0药动学软件处理血药浓度数据,用SPSS 19.0统计学软件对所得药动学数据进行统计学差异分析。结果:大鼠静脉注射单硝酸异山梨酯和阿魏酸钠后,两药单用以及联用的药动学过程均为三室模型。联合用药后,单硝酸异山梨酯的Vd和CL与单独用药时相比显著性降低,而阿魏酸的Vd、CL和t1/2与单独用药时相比显著性增加,两药的其他药动学参数MRT,AUC0-t则无显著性变化。结论:本方法可用于大鼠体内单硝酸异山梨酯和阿魏酸的药动学研究。单硝酸异山梨酯和阿魏酸钠联合用药后各自的药动学参数均发生明显变化,两药有药动学的相互作用。     

单硝酸异山梨酯盐酸伊伐布雷定复方对Beagle犬的长期毒性研究

目的观察Beagle犬连续30天口服单硝酸异山梨酯盐酸伊伐布雷定复方(ISMN-I)所产生的毒性反应,为临床剂量的拟定提供依据。方法 Beagle犬32只,雌雄各半,分为4组:空白对照组,复方低、中、高(30、75、180 mg·kg-1)剂量组,每组8只动物。每日给药1次,连续给药30天,停药观察14天。实验期间,每日进行一般状态观察,每周测定1次体质量及摄食量,于给药前、给药末期及停药恢复期末,各组动物分别进行眼科、体温、尿液、血压、心电图(Ⅱ导联)、血液学指标、血液生化学检测,给药期及恢复期结束剖检并进行病理组织学检查。结果 ISMN-I复方高剂量组、中剂量组给药末期可使舒张压(DBP)出现降低,且高剂量组、中剂量组均可导致Beagle犬在给药期间出现呕吐、振颤、抽搐、无力等反应,低剂量组个别犬偶尔出现一次性的呕吐反应。结论本试验条件下,单硝酸异山梨酯盐酸伊伐布雷定复方对Beagle犬无不良反应剂量(NOAEL)为30 mg·kg-1。     

尼索地平对单硝酸异山梨酯在小鼠体内组织分布的影响

目的考察尼索地平对单硝酸异山梨酯在小鼠体内组织分布的影响。方法 30只健康昆明种小鼠,♂,随机分成2组,分别为单独给药组和联合给药组,HPLC测定组织中单硝酸异山梨酯的浓度。结果小鼠组织中单硝酸异山梨酯浓度在给药后0.083 h为小肠>胃>心>肝>肾,给药后0.5 h为胃>小肠>肾>心>肝。胃中最大浓度出现时间因给药方案不同而异:单独给药组在给药后0.5 h单硝酸异山梨酯浓度最大,联合给药组在给药后0.083 h浓度最大。胃中单硝酸异山梨酯最大浓度,2组具有显著性差异(P<0.05)。结论尼索地平对单硝酸异山梨酯在小鼠组织中的分布具有一定影响。     

LC-MS/MS法测定比格犬血浆中芬太尼浓度及药动学研究

目的 建立比格犬血浆中芬太尼的液相色谱-串联质谱（LC-MS/MS）测定方法,并用于药动学研究。方法 采用固相萃取（SPE）法从血浆中提取芬太尼和内标芬太尼-d5,建立比格犬血浆中芬太尼的LC-MS/MS测定方法,进行特异性、准确度、精密度、基质效应、灵敏度、稀释可靠性、稳定性方法学验证;8只比格犬,分别单次iv给予芬太尼的生理盐水溶液400 mg/只,用LC-MS/MS测定给药后血浆中芬太尼浓度,并用WinNonLin软件计算药动学参数。结果 芬太尼的线性范围为2～1 000 pg/mL,精密度、准确度、基质效应、灵敏度、稀释可靠性、稳定性均符合生物样品分析要求。比格犬体内芬太尼药动学参数：t_1/2为（4.53±0.748）h,AUC_0-t为（19 659±3 889）h·ng/mL,CL为（2 259±284）mL/（h·kg）,符合二室开放模型。结论 建立的LC-MS/MS分析方法准确灵敏,适用于芬太尼的药动学研究。     

单硝酸异山梨酯对尼索地平在大鼠体内药代动力学的影响（英文）

目的:考察单硝酸异山梨酯对尼索地平在大鼠体内药代动力学的影响。方法:12只健康雄性SD大鼠随机分成2组(分别为单独和联合给药组),用LC-MS/MS法测定血浆中尼索地平的浓度。结果:大鼠单独给予尼索地平和联合给予单硝酸异山梨酯后,尼索地平主要药动学参数如下:Cmax分别为(8.67±3.97)μg/L和(9.21±5.02)μg/L,AUC0-t分别为(19.6±9.9)μg·h·L-1和(25.7±13.7)μg·h·L-1,t1/2分别为(2.26±0.66)h和(3.17±1.41)h,AUC0-∞分别为(23.7±9.7)μg·h·L-1和(32.4±12.3)μg·h·L-1。统计学分析显示,单独用药与联合用药组药动学参数无统计学差异(P>0.05)。结论:单硝酸异山梨酯不影响尼索地平在大鼠体内药动学过程,为临床安全有效地联用单硝酸异山梨酯和尼索地平提供了实验依据。     

尼可地尔联合单硝酸异山梨酯治疗不稳定型心绞痛的临床疗效

目的 探讨尼可地尔联合单硝酸异山梨酯治疗不稳定型心绞痛(UA)的临床疗效。方法 选择2017年1月至2018年12月在安徽省胸科医院心血管内科住院治疗的UA患者100 例,按照随机数字表法分为A组(30例)、B组(35例)与C组(35例),A组患者常规对症治疗,B组患者加用单药尼可地尔,C组患者加用尼可地尔联合单硝酸异山梨酯。3组患者均常规使用抗血小板、降脂及稳定斑块等基础治疗,观察3组患者6 min 步行试验及电话随访6个月内的再入院率。结果 3组患者用药前6 min步行距离差异无统计学意义(P>0.05),用药后6 min步行距离与用药前比较,差异有统计学意义(P<0.05)。用药后,3组患者6 min步行距离及差值比较,差异有统计学意义(P<0.05)。3组患者总有效率分别为53.33%、65.71%和88.57%,再入院率分别为 63.33%、31.43%和11.43%,3组患者总有效率、再入院率的差异均有统计学意义(P<0.05)。结论 UA患者使用尼可地尔联合单硝酸异山梨酯可明显改善症状,同时提高运动耐量,降低再入院率。     

伊曲康唑对双氯芬酸在比格犬体内药动学的影响

摘 要 目的：研究伊曲康唑对双氯芬酸钠在比格犬体内药动学参数的影响。方法: 采用随机交叉试验方法,一组口服双氯芬酸钠,另一组同时口服双氯芬酸钠和伊曲康唑,清洗期1周后,两组交叉服用药物。用HPLC法测定比格犬合用伊曲康唑前后双氯芬酸的血药浓度,并对其药动学参数进行分析。结果: 较单独给予双氯芬酸钠,合用伊曲康唑使双氯芬酸钠血药浓度曲线下面积(AUC_0-∞)与最大血药浓度C_max分别降低31%和42%。而达峰时间和半衰期并无显著差异(P>0.05)。结论:伊曲康唑可能通过影响双氯芬酸的胃肠道吸收过程,来影响AUC_0–∞和C_max。     

伊伐布雷定及其代谢物的血药浓度测定及人体药动学研究

目的：建立伊伐布雷定（IVA）及其活性代谢产物N-去甲基伊伐布雷定（M1）人体血药浓度的HPLC-MS/MS同时测定方法,研究盐酸伊伐布雷定片经健康受试者口服后IVA及M1的人体药代动力学特征。方法：12名健康受试者单次口服盐酸伊伐布雷定片2.5 mg、5 mg和7.5 mg,多次口服5 mg后,采用HPLC-MS/MS测定不同时间点血浆中IVA和M1浓度,并计算其主要药动学参数。结果：IVA和M1血药浓度标准曲线线性范围分别为0.03~80 ng·mL^-1和0.03~10 ng·mL^-1。单次给药2.5、5、7.5 mg后IVA的C_max分别为（9.661±3.832）、（20.63±9.31）、（34.95±19.46） ng·mL^-1,AUC0-48分别为（42.16±19.53）、（85.86±44.85）、（133.6±65.7） μg·h·L^-1;M1的C_max分别为（1.007±0.189）、（2.683±0.675）、（4.064±1.172） ng·mL^-1,AUC_0-48分别为（10.78±1.35）、（26.02±4.91）、（36.24±7.90） μg·h·L^-1。多次给药5 mg后IVA的稳态平均血药浓度Cav为（6.494±2.385） ng·mL^-1,稳态血药浓度波动度DF为（3.3±0.7）,累积常数R_AUC为（1.1±0.2）;M1的C_av为（1.959±0.186） ng·mL^-1,DF为（1.4±0.3）,R_AUC为（1.5±0.2）。结论：建立的人血浆中IVA和M1的LC-MS/MS同时测定方法适用于人体药代动力学研究。单次给药后,在2.5~7.5 mg范围内IVA和M1均呈线性药动学特征;多次给药5 mg后,IVA人体内的暴露量约增加10%,M1人体内的暴露量约增加50%。     

UPLC-MS/MS测定血浆中伊伐布雷定及其活性代谢产物的含量

目的 建立超高效液相色谱-串联质谱法测定人血浆中伊伐布雷定及其活性代谢产物(N-去甲伊伐布雷定)的含量。方法 选用Waters Acquity BEH C₁₈(50 mm×2.1 mm,1.7 μm)色谱柱,流动相为0.1%甲酸水溶液(A)-乙腈(B),梯度洗脱;流速为0.4 mL·min^-1;电喷雾离子源,多反应监测。伊伐布雷定：[M+H]⁺,m/z 469.3→177.2,N-去甲伊伐布雷定：[M+H]⁺,m/z 455.2→262.2,卡马西平：[M+H]⁺,m/z 237.1→194.2。结果 伊伐布雷定线性范围为0.2~100 ng·mL^-1(r=0.998 1),N-去甲伊伐布雷定线性范围为0.05~25 ng·mL^-1(r=0.993 1);两者日间、日内精密度均<15%,方法回收率>90%,稳定性较好。结论 该方法快速、灵敏、重复性好,适用于血浆中伊伐布雷定及其代谢产物含量测定。     

注射用酒石酸长春瑞滨胶束及注射用长春瑞滨在比格犬体内的毒动学比较

目的 测定连续给予注射用酒石酸长春瑞滨胶束的毒动学参数，并与注射用酒石酸长春瑞滨进行比较。方法 选取16只比格犬随机分为4组，雌雄各半，分别连续iv给予注射用酒石酸长春瑞滨胶束低、中、高剂量（0.29、0.58、1.174 mg/kg）与注射用酒石酸长春瑞滨1.174 mg/kg，建立测定比格犬血浆中酒石酸长春瑞滨浓度的液相色谱-串联质谱（LC-MS/MS）法，测定血药浓度，采用DAS3.1.4药动学软件计算动力学参数。结果 比格犬iv给予注射用酒石酸长春瑞滨胶束低、中、高3个剂量，血药浓度、AUC_（0-t）、C_max随给药剂量的增加而增大；连续iv给药，低、中、高剂量组动物血药浓度、AUC_（0-t）、C_max在给药第1、29、71天时均变化不大，无明显蓄积倾向。而注射用长春瑞滨胶连续iv给药后随给药时间延长，动物血药浓度、AUC_（0-t）、C_max有上升趋势，AUC_（0-t）蓄积因子分别为2.08、1.80，C_max蓄积因子分别为2.58、2.32，均有蓄积倾向。结论 注射用酒石酸长春瑞滨胶束与普通注射用酒石酸长春瑞滨毒动学参数比较，无明显的蓄积倾向，可降低长期服药的毒性风险。     

Contribution of isosorbide-5-mononitrate, a major metabolite of isosorbide dinitrate (ISDN), to the hemodynamic effect of ISDN administered orally in conscious dogs

This study was designed to determine the extent, to which isosorbide-5-mononitrate (5-ISMN) contributes to the hemodynamic effect of isosorbide dinitrate (ISDN) in conscious dogs. Test drugs (ISDN or 5-ISMN) were given orally. Either ISDN or 5-ISMN produced a decrease in blood pressure dose-dependently, the decrease in pulse pressure being specific; the pattern of blood pressure change induced by ISDN or 5-ISMN was different from that induced by nifedipine or prazosin. The effect of ISDN (2 mg/kg) was almost equivalent to that of 5-ISMN (4 mg/kg) and the effect of ISDN (4 mg/kg) to that of 5-ISMN (8 mg/kg). After administration of ISDN, both ISDN and 5-ISMN appeared in the plasma, and the effect of ISDN well-correlated with the increase in the plasma concentration of 5-ISMN. Contribution of 5-ISMN to the effect of ISDN was estimated to be about 30% from the value of the plasma concentration of 5-ISMN at 3 to 4 hr after administration, when the maximal response to ISDN occurred. Based on the data of the area under the plasma concentration curve of 5-ISMN (from 0 to 10 hr after administration), the fraction of biotransformation to 5-ISMN from ISDN was calculated to be 73.6 to 76.6% (based on moles). Because the ability of 5-ISMN to decrease pulse pressure was about 1/2 (or 41% based on moles) of that of ISDN, the contribution of 5-ISMN to the effect of ISDN was estimated to be about 30% in total, the value being similar with that estimated at 3 to 4 hr after administration.     

冠心康胶囊联合伊伐布雷定治疗顽固性心力衰竭的临床研究

目的 探讨冠心康胶囊联合盐酸伊伐布雷定片治疗顽固性心力衰竭的临床疗效。方法 选取2020年5月—2022年6月在衡水市中医医院就诊的128例顽固性心力衰竭患者,根据随机数字表法将所有患者分为对照组和治疗组,每组各64例。对照组口服盐酸伊伐布雷定片,5 mg/次,2次/d。治疗组在对照组基础上口服冠心康胶囊,4粒/次,3次/d。两组连续治疗3个月。观察两组的临床疗效,比较两组患者心功能指标和血清因子水平。结果 治疗后,治疗组患者的总有效率为92.19%,明显高于对照组的总有效率79.69%,差异有显著意义（P<0.05）。治疗后,两组的左心室射血分数（LVEF）高于治疗前,左心室舒张末期后壁厚度（LVPWT）低于治疗前（P<0.05）;治疗组的LVEF高于对照组,LVPWT低于对照组差异有统计学意义（P<0.05）。治疗后,两组的血清血管紧张素-2(Ang-2)、血管紧张素转换酶2(ACE2)、N末端脑钠肽前体（NT-proBNP）水平明显降低（P<0.05）,且治疗组血清Ang-2、ACE2、NT-proBNP水平明显低于对照组（P<0.05）。结论冠心康...     

氯沙坦对2型糖尿病大鼠体内格列吡嗪药动学的影响

目的探讨氯沙坦对格列吡嗪在2型糖尿病大鼠体内药动学参数的影响。方法以高糖高脂饲料喂养、ip低剂量链脲佐菌素诱导2型糖尿病模型大鼠为研究对象,ig氯沙坦片5 mg/kg,给药1 h后ig格列吡嗪5 mg/kg,于给药后1、2、3、4、5、6、8、10、12h采集血浆样品,采用HPLC法测定血浆中的格列吡嗪质量浓度,绘制其血浆平均药物浓度–时间曲线;计算格列吡嗪在大鼠体内的主要药动学参数。结果与健康大鼠比较,格列吡嗪在2型糖尿病大鼠体内消除半衰期明显延长(P0.05)。在2型糖尿病大鼠中,与单用格列吡嗪比较,格列吡嗪的达峰浓度(Cmax)、时量曲线下面积(AUC)明显增加(P0.05),达峰时间(tmax)明显减小(P0.05)。结论在糖尿病病理状态下,格列吡嗪的药动学发生了一定的改变。联合用药时,氯沙坦可明显提高格列吡嗪的血药浓度和生物利用度。     

Hepatoprotective effects of the nitric oxide donor isosorbide-5-mononitrate alone and in combination with the natural hepatoprotectant, silymarin, on carbon tetrachloride-induced hepatic injury in rats

The aim of this study was to investigate the effect of the nitric oxide donor isosorbide-5-mononitrate (5-ISMN) alone or in combination with the natural hepatoprotectant with anti-oxidant activity silymarin on the carbon tetrachloride (CCl₄)-induced hepatic injury in rats. 5-ISMN (1.8, 3.6 or 7.2 mg/kg), silymarin (25 mg/kg) or 5-ISMN (1.8, 3.6 or 7.2 mg/kg) combined with silymarin was given once daily orally simultaneously with CCl₄ and for 15 days thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. 5-ISMN given at the above doses conferred significant protection against the hepatotoxic actions of CCl₄ in rats, reducing serum alanine aminotransferase (ALT) levels by 31.2, 39.3 and 61.6%, respectively, when compared with controls. Serum aspartate aminotransferase (AST) levels decreased by 19.8, 22.7 and 59.4%, respectively, while alkaline phosphatase (ALP) decreased by 26.1 and 32.6% by the drug at 3.6 and 7.2 mg/kg, respectively. When silymarin was added to 5-ISMN (1.8, 3.6 or 7.2 mg/kg), ALT decreased by 32.8, 59.6, 70.2% and AST by 28.7, 50.3, 60%, when compared with CCl₄ control group levels. Silymarin in combination with 3.6 or 7.2 mg/kg 5-ISMN resulted in 37.5 and 39.2% reductions in ALP when compared with CCl₄ control group. Meanwhile, silymarin alone reduced ALT, AST and ALP levels by 65.9, 52 and 62.3%, respectively. Blood levels of reduced glutathione were markedly decreased in CCl₄-treated rats. Reduced glutathione levels were increased by the administration of 5-ISMN and restored to near normal values by silymarin treatment. Histopathological alterations by CCl₄ were markedly reduced after treatment with 5-ISMN alone or in combination with silymarin. Histopathologic examination of the livers of CCl₄-treated rats administered 5-ISMN at 7.2 mg/kg showed marked restoration of the normal architecture of the liver tissue and minimal fibrosis. Silymarin co-administered with 5-ISMN resulted in further improvement of the histologic picture. These results indicates that treatment with 5-ISMN protects against hepatocellular necrosis induced by CCl₄. The study suggests a potential therapeutic use for 5-ISMN in combination with silymarin in liver injury.     

Stereoselective Pharmacokinetics and Pharmacodynamics of Propylisopropyl Acetamide,a CNS-Active Chiral Amide Analog of Valproic Acid

Purpose. The purpose of this study was to evaluate there existed stereoselective effects in the pharmacokinetics, anticonvulsant activity, microsomal epoxide hydrolase (mEH) inhibition, and teratogenicity of the two enantiomers of propylisopropyl acetamide (PID), a CNS-active chiral amide analogue of valproic acid. Methods. Racemic PID, as well as the individual enantiomers, were intravenously administered to six dogs in order to investigate the stereoselectivity in their pharmacokinetics. Anticonvulsant activity was evaluated in mice (ip) and rats (oral), mEH inhibition studies were performed in human liver microsomes, and teratogenicity was evaluated in an inbred susceptible mice strain. Results. Following intravenous administration to dogs of the individual enantiomers, (R)-PID had significantly lower clearance and longer half-life than (S)-PID, however, the volumes of distribution were similar. In contrast, following intravenous administration of racemic PID, both enantiomers had similar pharmacokinetic parameters. In rats (oral), (R)-PID had a significantly lower ED₅₀ in the maximal electroshock seizure test than (S)-PID; 16 and 25 mg/kg, respectively. PID enantiomers were non-teratogenic and did not demonstrate stereoselective mEH inhibition. Conclusions. (R)-PID demonstrated better anticonvulsant activity, lower clearance and a longer half-life compared to (S)-PID. When racemic PID was administered, the clearance of (S)-PID was significantly reduced, reflecting an enantiomer-enantiomer interaction.     

The Pharmacokinetics of Topotecan and Its Carboxylate Form Following Separate Intravenous Administration to the Dog

Purpose. To determine the relationship between topotecan and its ring opened hydrolysis product (SK&F 105992) following intravenous administration of the two agents separately, and to determine the bio-availability of topotecan in female beagle dogs. Methods. The pharmacokinetics of topotecan and SK&F 105992 were determined following separate administration as 30 minute intravenous infusions in a cross-over design. Topotecan was also administered orally to the same dogs. Results. When administered intravenously to dogs, SK&F 105992 underwent interconversion to topotecan. Plasma concentrations of both topotecan and SK&F 105992 appeared to decline multi-exponentially following IV infusion of either compound. A 2-compartment model was found to adequately characterize the data. Conclusions. The clearance of topotecan by other routes proceeded at a faster rate than its interconversion to SK&F 105992, whereas the clearance of SK&F 105992 by other routes was slower than the rate of its interconversion to topotecan. Any SK&F 105992 formed in the GI tract did not appear to be well absorbed following oral administration of topotecan to dogs. The steady-state volume of distribution for topotecan was approximately 8- to 9-fold greater than that for SK&F 105992 in the dog. After intravenous administration of topotecan, the amount of topotecan in the dog was much greater than that of the carboxylate, even though their respective plasma concentrations were similar. The bioavailability of topotecan, calculated from oral topotecan data or from SK&F 105992 data, was approximately 50%.     

脑心通胶囊对缬沙坦在大鼠体内药动学的影响

目的 研究脑心通胶囊对缬沙坦在大鼠体内药动学的影响。方法 建立液相色谱-串联质谱（LC-MS/MS）法检测缬沙坦血药浓度,并进行专属性考察、回收率试验、基质效应、稳定性试验等方法学验证;24只SD雄性大鼠,随机均分为3组,每组8只,分别为缬沙坦组（A组）,缬沙坦和脑心通胶囊单次给药组（B组）,脑心通胶囊给药7 d后,第8天ig给予缬沙坦和脑心通胶囊组（C组）,于给药前及给药后不同时间点由大鼠眼眶静脉丛采血,采用液相色谱-串联质谱（LC-MS/MS）法测定血浆中缬沙坦的质量浓度,DAS2.0软件统计分析,得到缬沙坦的药动学参数。结果 成功建立LC-MS/MS法检测缬沙坦血药浓度方法,方法学验证符合药动学相关规范要求。口服缬沙坦在大鼠体内的药动学属于一室模型。B组C_max明显低于A组,但差异无统计学差异;B组t_1/2显著高于A组（P<0.05）;C组t_max、t_1/2、AUC_0-tn、AUC_0-∞均显著高于A组（P<0.05、0.01）,K_e显著低于A组（P<0.05）;C组AUC_0-tn、AUC_0-∞显著高于B组（P<0.05）。结论 大鼠经连续ig给药脑心通胶囊后,可显著延缓缬沙坦在大鼠体内的达峰时间,并使缬沙坦在大鼠体内的生物利用度升高。     

Investigation of a possible pharmacokinetic interaction between ibopamine and isosorbide-5-mononitrate

Summary The possibility of a pharmacokinetic interaction between isosorbide-5-mononitrate (5-ISMN) and epinine, the active metabolite of ibopamine, has been investigated in 8 healthy male subjects given single doses of 200 mg ibopamine and 20 mg 5-ISMN, separately and together.The plasma 5-ISMN concentration-time profile was the same whether 5-ISMN was administered concomitantly with ibopamine or alone [AUC(o-t): 2.24 g·ml^–1·h after 5-ISMN alone, 2.16 g·ml^–1·h after 5-ISMN + ibopamine]. The plasma concentrations of total and free epinine and the urinary recovery of total epinine, homovanillic acid and dihydroxyphenylacetic acid, too, were not different when ibopamine was administered alone or concomitantly with 5-ISMN. The intake of ibopamine did not change the blood pressure and heart rate. The decrease in diastolic blood pressure induced by 5-ISMN was not influenced by concomitant intake of ibopamine.The observations suggest that in healthy volunteers there is no pharmacokinetic interaction between 5-ISMN and ibopamine.     

活心丸联合伊伐布雷定治疗稳定型心绞痛的临床研究

目的 探讨活心丸联合盐酸伊伐布雷定片治疗稳定型心绞痛的临床疗效。方法 选取2021年4月—2023年5月来宾市兴宾区人民医院收治的102例稳定型心绞痛患者,按照随机数字表将患者分为对照组（51例）和治疗组（51例）。对照组口服盐酸伊伐布雷定片,1片/次,2次/d。治疗组在对照组基础上口服活心丸,2丸/次,2次/d。治疗8周分析治疗效果。比较两组的总有效率、心绞痛症状、冠状动脉血管狭窄程度和血清指标。结果 治疗后,治疗组的总有效率为94.12%,对照组的总有效率为80.39%,组间差异明显（P<0.05）。治疗后,两组的心绞痛发作频率、疼痛持续时间、视觉模拟评分法（VAS）评分、Gensini评分均显著降低（P<0.05）;治疗组的心绞痛发作频率、疼痛持续时间、VAS评分、Gensini评分低于对照组（P<0.05）。治疗后,两组的血清氧化性低密度脂蛋白受体-1(LOX-1)、高迁移率族蛋白1(HMGB1)水平低于治疗前,血清可溶性晚期糖基化终末产物受体（SRAGE）水平高于治疗前（P<0.05）;治疗组的血清LOX-1、HMGB1水平低于对照组,血清SRAGE水...     

Influence of electric foot shock on pharmacokinetics of isosorbide dinitrate subcutaneously administered to rats

The influence of emotional stress on the pharmacokinetics of isosorbide dinitrate (ISDN) administered s.c. to rats was studied. The plasma level of ISDN in emotionally stressed (ES) rats was the same as that in non-stressed control rats. However, the levels of its metabolites, 5-isosorbide mononitrate (5-ISMN) and 2-isosorbide mononitrate (2-ISMN), were markedly lower in ES rats than in the control rats. On the other hand, urine ISDN and 2-ISMN excretion rates were lower in ES rats than in the control rats. These observations suggest that the pharmacokinetics of ISDN administered s.c. is influenced by emotional stress such as foot shock.