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1.
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 Cmax was higher (39.0 ng·ml-1) and tmax 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 (emax=130%) and the time to emax (temax) 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. 相似文献
2.
PHILIPPE KIRSTETTER CHRISTOPHE PILETTE RICHARD MOREAU STEPHANE CAILMAIL VACLAV SAFKA THIERRY SOUPISON DIDIER LEBREC 《Journal of gastroenterology and hepatology》1996,11(3):230-235
The haemodynamic effects of nitrovasodilators and their mechanisms of action on portal hypertension remain unclear. The splanchnic and systemic haemodynamic response to the infusion of isosorbide dinitrate (100 μg/kg per min), a nitrovasodilator, was investigated in cirrhotic rats. The role of the conscious state in the haemodynamic response to isosorbide dinitrate was examined using rats that were anaesthetized with pentobarbitone. The role of sympathetic tone in the haemodynamic response to isosorbide dinitrate was examined using rats pretreated with the ganglion blocker hexamethonium. Isosorbide dinitrate had no haemodynamic effects in conscious, unblocked normal and cirrhotic rats. Isosorbide dinitrate had no haemodynamic effects in normal and cirrhotic rats treated with hexamethonium. In normal anaesthetized rats, isosorbide dinitrate significantly decreased systemic vascular resistance (414±25 vs 290±26 dyn.s/cm5 per 100 g). In cirrhotic anaesthetized rats, isosorbide dinitrate significantly decreased mean arterial pressure (98±6 vs 79±7 mmHg), systemic vascular resistance (318±30 vs 207±10 dyn.s/cm5 per 100 g), portal pressure (14.0±1.0 vs 11.3±0.9 mmHg) and portal territory vascular resistance (1362±163 vs 1031±182 dyn.s/cm5 per 100 g). In conclusion, this study shows that the portal hypotensive effects of isosorbide dinitrate depend upon the alterations of vascular tone by pentobarbitone. 相似文献
3.
Arterial blood pressure and heart rate were measured in 43 patientswith acute myocardial infarction and a systolic blood pressure120 mmHg during sublingual administration of 5 mg of isosorbidedinitrate. In 25 of them right heart haemodynamics were alsomeasured. Severe (25%) hypotension developed in 12 patients(Group 1, systolic blood pressure 158 ± 28 to 78 ±17 mmHg, mean ± SD) but not in the remaining 31 (Group2) and was accompanied by a fall in heart rate (82 ±20 to 70 ± 22beats min-1, P<0.05), in cardiac output(4.3 ± 0.3 to 3.2 ± 0.4l mm-1, P<0.02, n =5) and in systemic vascular resistances (2326 ± 463 to1532 ± 442 dynes sec-1 cm-5, P<0.02) not present inGroup 2. The reduction in right (Group 1,8 ± 3 to 3 ±1, vs. Group 2,10 ± 3 to 6± 3 mmHg, V <0.005)and in left ventricular filling pressures (Group 1,15 ±4 to 8 ± 2, vs. Group 2,18 ± 6 to 13 ±5 mmHg, P<0.001) was more remarkable in Group 1. In thisgroup there was also a high incidence of anterior infarction(9/12, 75%). Blood volume measured in 30 patients was lowerin Group 1 but differences were not significant. A second doseof 5 mg of isosorbide dinitrate 3648 h later producedneither symptomatic hypotension (Group 1, 147 ± 29 to129 ± 24 mmHg) nor a fall in cardiac output in any patient,whereas changes infilling pressures were comparable to thoseof the first dose. Thus, severe isosorbide dinitrate-induced hypotension in myocardialinfarction is limited to the acute phase and seems more prevalentin anterior infarction but can not be clearly predicted fromresting haemodynamic or blood volume measurements, at leastin non-hypotensive patients. Moreover, it appears to be causedby an excessive ventricular emptying due to a striking venousand arterial vasodilation, probably during a stage of a particularlydepressed ventricular compliance. 相似文献
4.
复方丹参滴丸抗心绞痛临床观察 总被引:7,自引:0,他引:7
目的 观察复方丹参滴丸抗心绞痛的疗效和耐药性,并与消心痛的疗效进行比较。方法 将病人随机分为A组和B组,以双盲方式给药观察8周。A组口服复方丹参滴丸10粒/次、3次/d,B组口服消心痛10mg/次、3次/d。结果 心绞痛有效率,ECG有效率用药2周时两组无显著差异,用药后第4周、第6周和第8周A组优于B组。用药后第6周与第2周的有效率比较,A组无明显变化(P>0.05),B组显著下降(P<0.05)。结论 与消心痛相比较,长期服用复方丹参滴丸的有效率高,疗效稳定,且不产生耐药性。 相似文献
5.
6.
Volker B. Fiedler Rolf-Eberhard Nitz 《Naunyn-Schmiedeberg's archives of pharmacology》1981,317(1):71-77
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. 相似文献
7.
目的探讨无症状性心肌缺血患者使用麝香保心丸与硝酸异山梨酯联合治疗后的临床效果。方法选择来我院就诊的无症状性心肌缺血患者72例作为本次研究对象,随机分为两组。观察组(n=36)采用麝香保心丸联合硝酸异山梨酯进行治疗,对照组(n=36)采用硝酸异山梨酯进行治疗,对两组患者的心电图心肌缺血改善情况及血脂、血液动力学观察指标进行对比分析。结果观察组患者与对照组比较,心电图缺血改善情况中有效率明显较高,两组差异具有显著性(P〈0.05)。治疗后观察组患者的全血黏度高切值、全血黏度低切值、血浆比黏度、TG、TC均显著降低,与对照组治疗后比较改善情况明显较好(P〈0.05)。所有患者治疗后均未发现不良情况。结论无症状性心肌缺血患者在采用麝香保心丸联合硝酸异山梨酯治疗后能够收到较好的临床效果。可以在临床推广应用。 相似文献
8.
The effects of various vehicles and adhesives on the percutaneous absorption of isosorbide dinitrate (ISDN) were evaluated. Lauroglycol ® FCC showed the highest flux among vehicles tested. The flux of ISDN from silicone and acrylic adhesive matrices was found to be higher than that from other types of adhesive matrices. No statistically significant relationship between the flux from acrylic PSA and the flux from a solution formulation was observed. A highly cross-linked acrylic adhesive gave higher permeation rates than the other acrylic adhesives examined. N-decylmethyl sulfoxide showed the highest enhancing effect on the flux of ISDN from acrylic adhesive. The relationship between the HLB values of vehicles and the measured flux showed a decrease of flux at HLB values greater than 12. 相似文献
9.
目的:比较分析中西医结合治疗与单纯西药治疗冠心病劳力型心绞痛的疗效,以为今后临床本病的治疗提供参考。方法114例冠心病合并劳力型心绞痛患者,随机分为中西医结合治疗组(观察组,60例)以及西药治疗组(对照组,54例),对照组给予单硝酸异山梨酯片治疗,观察组在对照组基础上联合自制中药汤剂治疗。观察两组疗效。结果观察组显效34例,有效18例,无效8例,总有效率为86.7%,对照组患者显效18例,有效20例,无效为16例,总有效率为70.4%,观察组总有效率明显高于对照组,差异具有统计学意义(P<0.05)。两组均有个别患者有副作用,经对应调节后副作用均消失,所有患者均坚持全程服药。结论中西医结合治疗冠心痛劳力型心绞痛疗效显著,值得临床应用推广。 相似文献
10.
SCHNEIDER W.; MAUL F.-D.; BUBMANN W.-D.; LANG E.; HOR G.; KALTENBACH M. 《European heart journal》1988,9(2):149-158
Fourteen male patients with exertion-related angina pectorisand reproducible ST-segment depression on stress testing wereeach treated with isosorbide dinitrate (ISDN) 40 mg three timesdaily, verapamil 120 mg three times daily and placebo threetimes daily for two weeks according to a double-blind cross-overprotocol. The mean improvement of exercise-induced ST-segment depressionamounted to 73% on the first day of ISDN treatment (P < 0.001)and to 54% following acute administration of verapamil (P <0.001). On the last day of continuous treatment, the antianginalefficacy of ISDN was somewhat mitigated (reduction of ST-segmentdepression: 54%; P<0.001), while the effect of verapamilremained unchanged (55%, P<0.001). The double product (heartrate x systolic blood pressure) at the end of stress testingdecreased most pronouncedly on day 1 of ISDN treatment ( - 21%;P<0.01). On chronic testing, both drugs similarly influencedthis parameter: 1011% (P<0.05). The mean global ejectionfraction (EF) assessed by gated blood pool scintigraphy on day13 showed a stress-induced fall from 49 to 44% (P<0.05) afterthe administration of placebo. The respective values with ISDNwere 53% at rest and 52% on exercise (n.s.), and after givingverapamil 50% and47% (n.s.). Thus, ISDN 40 mg and verapamil 120 mg displayed beneficial anti-ischaemiceffects in patients with stable exertion-related angina pectorisafter acute and chronic administration. The efficacy of ISDNdeclined somewhat in the course of the two-week treatment, whereasthat of verapamil remained unchanged. Beneficial effects ofboth drugs were also demonstrated with regard to the rate pressureproduct. Isosorbide dinitrate 40 mg and verapamil 120 mg administeredthree times daily can be recommended for the acute and chronictherapy of patients with stable angina. 相似文献