Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration

The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 16 healthy volunteers.After the sublingual spray C_max was higher (39.0 ng·ml^-1) and t_max was shorter (3.9 min) than after the sublingual (22.8 ng·ml^-1 and 13.8 min) and peroral (16.9 ng·ml^-1 and 25.6 min) tablets. The AUC of ISDN did not differ following any of the three formulations (1031; 879; 997 ng·ml^-1·min, for the spray, SL tablet and PO-tablet, respectively). Mononitrate metabolites of ISDN (IS-2-MN and IS-5-MN) and total nitrates in plasma increased in proportion to the administered dose. This indicates that the fraction of the dose absorbed was the same for all the formulations but that the extent of first-pass metabolism increased in the order sublingual spray < sublingual tablet < peroral tablet. Thus, compared to the spray, the relative bioavailability of ISDN was 48% and 28% from the sublingual and peroral tablets, respectively.The haemodynamic effects were quantified using the a/b ratio of the finger pulse wave and the systolic blood pressure and heart rate under orthostatic conditions. For the a/b ratio of the finger pulse, the maximal effect was higher (e_max=130%) and the time to e_max (t_emax) shorter (16.6 min) after the spray than the sublingual tablet (84.4% and 25.5 min) or peroral tablet (90.2 and 31.3 min). The onset of effect was within 3, 5 and 7.5 min after the spray, sublingual and peroral tablets, respectively. A larger change in the orthostatically-induced decrease in systolic blood pressure and increase in heart rate was obtained following peroral than sublingual administration despite the similar plasma concentrations of ISDN. This probably reflects the larger amount of pharmacodynamically active mononitrate metabolites formed after oral dosing. The integrated effect following administration of 2.5 mg ISDN as spray was similar to that of a sublingual tablet of 5 mg.     

Effects of molsidomine,nitroglycerin, and isosorbide dinitrate on the coronary circulation,myocardial oxygen consumption,and haemodynamics in anaesthetized dogs

Summary The effects of i.v. molsidomine administration on the coronary circulation, myocardial oxygen consumption, and haemodynamics were studied in open-chest dogs with non-constricted coronary arteries, and compared to those of nitroglycerin and isosorbide dinitrate. Molsidomine (50, 100, 250 g/kg) reduced coronary flow while nitroglycerin (5, 10, 20 g/kg) and isosorbide dinitrate (50, 100, 250 g/kg) augmented coronary flow indicating coronary dilatation. Coronary resistance remained unaffected by molsidomine but fell after both nitrates. Molsidomine decreased myocardial oxygen consumption whereas nitroglycerin and isosorbide dinitrate initially increased oxygen consumption followed by a reduction. A decrease in stroke work was calculated after all three drugs. Minute work fell after molsidomine and nitroglycerin but not after isosorbide dinitrate.Heart rate and contractility remained unchanged by molsidomine but were both significantly enhanced by both nitrates. Stroke volume and cardiac output fell after molsidomine but increased immediately after both nitrates when administered with a subsequent decrease. Peripheral resistance was unchanged by the low dose of molsidomine but significantly decreased by the two nitrates immediately after administration indicating precapillary vasodilatation. The fall in blood pressure after molsidomine followed the reduction in cardiac output as sequel of lowered preload and venous return to the heart. The same mechanism decreased heart work after both nitrates but in addition vasodilatation of the coronary arteries and arterial vessel occurred.The effects of the three compounds are mainly the consequence of extracardiac effects, i.e. increased capacity of postcapillary vessels (molsidomine) plus arteriolar vasodilatation of short (nitroglycerin) and long duration (isosorbide dinitrate), respectively. Whereas molsidomine exerts no effects on the heart and coronary circulation both nitrates dilate coronary arteries and change heart performance thus indicating direct effects on the entire heart.     

复方单硝酸异山梨醇酯缓释片人体生物等效性研究

目的 :评价试验制剂复方单硝酸异山梨醇酯缓释片 (T)与参比制剂单硝酸异山梨醇酯缓释片和阿司匹林肠溶片 (R)的生物等效性 ,以及缓释制剂释放特点、稳态血浓度和波动度。方法 :采用高效液相色谱法分别测定单剂和多剂交叉给药单硝酸异山梨醇酯和阿司匹林代谢物水杨酸经时血浓度 ,计算药物动力学参数 ,并进行方差分析和双单侧t检验。结果 :单剂给药试验制剂和参比制剂单硝酸异山梨醇酯半衰期 (t1 2 )分别为 8.3± 0 .6、8.2± 0 .6h ,血浓度峰值 (Cmax)分别为 0 .5 1± 0 .0 9、 0 .5 3±0 .0 9mg·L-1,达峰时间 (tmax)分别为 4 .8± 0 .4、4 .6± 0 .3h ,药时曲线下面积 (AUC0 -t)分别为 4 .90±0 .6 1、5 .2± 0 .8mg·h-1·L-1,相对生物利用度 (F)为(96 .1± 10 .8) % ;试验制剂和参比制剂阿司匹林代谢物水杨酸t1 2 分别为 2 .4± 0 .3、2 .5± 0 .3h ,Cmax分别为 3.4± 0 .5、3.0± 0 .4mg·L-1,tmax分别为 1.7±0 .2h和 4 .9± 0 .3h ,AUC0 -t分别为 13.4± 2 .5和13.0± 2 .5mg·h-1·L-1,以水杨酸计阿司匹林F为(10 3.6± 9.6 ) %。多剂给药试验制剂和参比制剂单硝酸异山梨醇酯Cmax 分别为 0 .6 8± 0 .14、0 .6 7±0 .13mg·L-1,Cmin 分别为 0 .17± 0 .0 3、 0 .17±0 .0 4mg·L-1,波动系数 (DF)     

HPLC用于复方单硝酸异山梨酯-阿司匹林缓释片的质量分析

 目的建立用HPLC分析复方单硝酸异山梨酯-阿司匹林缓释片质量的方法。方法用高效液相色谱法检测复方单硝酸异山梨酯缓释片中药物的含量和释放度。色谱条件为：Hypersil C₁₈柱；甲醇-水(30∶70)加1‰磷酸调节pH值至3.0为流动相；流速为1 mL·min^-1；UV检测波长为235 nm。以乙腈为溶剂配制对照品溶液及样品溶液。结果复方中两种成分及阿司匹林水解产物水杨酸在20 min内达到良好分离。单硝酸异山梨酯、阿司匹林的线性范围分别为16.0～112.0 μg·mL^-1(r=0.999 9)，20.0～140.0 μg·mL^-1(r=0.999 9)。平均回收率分别为100.4%(RSD=0.66%)和100.7%(RSD=0.69%)。结论本法简便、快速，结果准确，可用于同类药品的质量标准研究和质量检验。     

中药瓜蒌香饮联合西药治疗冠心病对照观察

[目的]观察中药瓜蒌香饮联合西药治疗冠心病疗效。[方法]将2008年至2011年我院收治的100例冠心病患者随机分为治疗组与对照组各50例。对照组患者采用西医治疗,主要以抗血小板凝聚、降扩冠脉、抗心绞痛等为治疗原则。治疗组患者在对照组治疗方法的基础之上增加口服中药瓜蒌香饮,治疗30d为1疗程,疗程结束后将两组患者的治疗结果进行评估比较。[结果]治疗组显效29例,有效16例,无效5例,总有效率90.00%;对照组显效13例,有效24例,无效13例,总有效率74.00%。治疗组总有效率优于对照组。[结论]中药瓜蒌香饮联合西药治疗冠心病疗效优于单一的西医治疗。     

单硝酸异山梨酯、缬沙坦、螺内酯复方对大鼠的长期毒性研究

目的 观察SD大鼠连续6个月口服单硝酸异山梨酯、缬沙坦、螺内酯复方所产生的毒性反应,比较3种药物联合应用后,毒性是否增加或产生新的毒性。方法 健康SD大鼠200只,雌雄各半,分为5组：空白对照组、复方73、244、733 mg·kg-1及缬沙坦600mg·kg-1对照组,每组40只。给药体积为10mL·kg-1,每日ig给药1次,每周给药6d,连续给药6个月,停药观察4周。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3、6个月及停药4周后,各组动物分别进行血压、血液学、血液生化学指标检测,动物剖检并进行病理组织学检查。结果 复方73、244、733 mg·kg-1及缬沙坦600 mg·kg-1对照组血压出现明显降低,为复方药物药理作用结果。244、733 mg·kg-1及缬沙坦600 mg·kg-1对照组RBC、HCT、HGB及Ret均出现明显降低,肾功能指标CREA、UREA及电解质K＋明显升高,组织病理学检查肾脏出现明显病理学改变,当停药恢复期结束后,上述各指标恢复正常。结论 本试验条件下,单硝酸异山梨酯、缬沙坦、螺内酯复方口服6个月无不良反应剂量（NOAEL）为73 mg·kg-1,当大鼠6个月给药剂量达到244 mg·kg-1时,血液学、血钾及肾功出现明显毒性反应,停药后可恢复正常。复方中3种药物联合应用,同缬沙坦单独使用相比未见毒性增加或产生新的毒性。     

麝香保心丸联合硝酸异山梨酯注射液治疗不稳定型心绞痛90例临床护理

目的探讨麝香保心丸联合硝酸异山梨酯注射液治疗不稳定型心绞痛疗效及护理方法。方法将90例不稳定型心绞痛患者随机分为治疗组和对照组各45例,治疗组静脉滴注硝酸异山梨酯注射液同时口服麝香保心丸,对照组只静脉滴注硝酸异山梨酯注射液,均连续应用14d,观察两组临床症状,心电图及血流变学变化情况。结果治疗组心绞痛改善情况,心电图改善情况,血流变学变化情况均优于对照组,两组比较有显著性差异(P<0.05,P<0.01)。结论麝香保心丸联合硝酸异山梨酯注射液治疗不稳定型心绞痛能减轻心绞痛,改善心电图及血流变学指标,配合精心护理,疗效优于静脉滴注硝酸异山梨酯注射液。     

益气活血通脉汤联合单硝酸异山梨酯、阿司匹林治疗陈旧性心肌梗死临床评价

目的 探讨益气活血通脉汤联合单硝酸异山梨酯、阿司匹林治疗陈旧性心肌梗死的临床疗效,以及对患者N末端脑利钠肽原(NT-proBNP)、肌酸激酶-同工酶(CK-MB)、乳酸脱氢酶(LDH)水平的影响.方法 选取医院2018年1月至2020年1月收治的陈旧性心肌梗死患者84例,按随机数字表法分为观察组和对照组,各42例.两组...     

强心汤治疗阳虚水泛型冠心病慢性心力衰竭临床观察

目的 分析阳虚水泛型冠心病慢性心力衰竭患者采用强心汤治疗的临床效果.方法 回顾性分析收治的98例阳虚水泛型冠心病慢性心力衰竭患者临床资料(纳入时间:2017年9月—2019年9月),根据治疗方法将其分成2组,常规组(49例)患者采用鲁南欣康治疗,试验组(49例)患者采用强心汤联合鲁南欣康治疗,观察2组患者的临床治疗效果...     

乙酰丹参素单硝酸异山梨醇酯的合成及对心肌缺血／再灌注大鼠心脏的保护作用

目的：考察乙酰丹参素单硝酸异山梨醇酯（AcDI-302）对心肌缺血／再灌注（MIfR）大鼠的心肌保护作用,并与单硝酸异山梨醇酯（ISMN）进行比较。方法：常规制备大鼠MI/R（30min／3h）模型。随机分为假手术组,MI／R组,（MI／R＋ISMN）组,（MI／R＋AcDI-302）组。观察各组大鼠缺血30min再灌注3h心功能恢复情况和3h末血清中肌酸激酶（CK）、乳酸脱氢酶（LDH）活性和丙二醛（MDA）的水平及NO的含量。结果：MI／R＋AcDI-302组大鼠较ISMN组心肌梗死范围明显减小,血清中CK,LDH活性和MDA浓度也显著降低,左室收缩压（LVSP）、左室等容收缩／舒张期压力上升或下降最大速率（±dp／dtmax）显著提高。结论：AcDI-302对心肌缺血再灌注损伤大鼠的心肌有保护作用,作用强于ISMN。