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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of temocapril hydrochloride, a novel angiotensin converting enzyme inhibitor, in renal insufficiency (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 657-659 
    Details
    ISSN: 1432-1041
    Keywords: Temocapril, Renal insufficiency ; angiotensin-I converting enzyme inhibitor, pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of temocapril hydrochloride, a novel prodrug-type angiotensin-I converting enzyme (ACE) inhibitor, has been studied in patients with mild (Group II) to severe (Group III) renal insufficiency in comparison with subjects with normal renal function (Group I). The pharmacokinetic parameters of the active diacid metabolite, including Cmax, AUC and half-life (t1/2), showed only slight changes between the three groups: AUC (0–∞) was significantly larger in Group III than Group I, and t1/2 tended to be prolonged in Group III, but the change was not significant. The urinary recovery of the diacid was significantly decreased in Group III. (Group I, 28.1 %, Group II, 21.6 %, Group III, 12.8 %). Compared with other ACE inhibitors, which are mainly excreted through the kidney, the plasma concentration of the active diacid metabolite was hardly influenced by renal function. It was speculated that lowering of the dose of temocapril might be recommended only in patients with severe renal insufficiency.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02284968
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  • 2
    Electronic Resource
    Electronic Resource
    Pilsicainide, a New Class I Antiarrhythmic Drug (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Cardiovascular drug reviews 11 (1993), S. 0 
    Details
    ISSN: 1527-3466
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1527-3466.1993.tb00267.x
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  • 3
    Electronic Resource
    Electronic Resource
    M6434, A Novel Anti-Circulatory-Shock Agent (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Cardiovascular drug reviews 8 (1990), S. 0 
    Details
    ISSN: 1527-3466
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1527-3466.1990.tb00402.x
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  • 4
    Electronic Resource
    Electronic Resource
    Cardiovascular Pharmacological Characteristics of S-2150: A Novel Dual Blocker of Calcium Channels and α1-Adrenoceptors (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Cardiovascular drug reviews 15 (1997), S. 0 
    Details
    ISSN: 1527-3466
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1527-3466.1997.tb00338.x
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  • 5
    Electronic Resource
    Electronic Resource
    Ro 22-9194: A New Class I Antiarrhythmic Agent (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Cardiovascular drug reviews 14 (1996), S. 0 
    Details
    ISSN: 1527-3466
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1527-3466.1996.tb00313.x
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  • 6
    Electronic Resource
    Electronic Resource
    Phase I clinical studies of S-1090: Safety and pharmacokinetics (1996)
    Springer
    Journal of infection and chemotherapy 2 (1996), S. 271-279 
    Details
    ISSN: 1437-7780
    Keywords: S-1090 ; oral cephem antibiotic ; phase I clinical studies ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract S-1090, an oral cephem antibiotic, was given to healthy male volunteers in single (10 to 400 mg) and multiple (200 mg, twice a day) doses. There were no abnormalities in subjective and objective signs, or physical findings, in any subjects. The intestinal and oropharyngeal bacterial flora were not significantly affected by S-1090. These results suggest that S-1090 is a safe and well-tolerated drug. Food intake increased the absorption of S-1090, but did not affect its half-life. The plasma concentration increased with increasing doses, but at a rate less than proportional to the dose, in the single-dose studies. S-1090 was eliminated with a half-life of 2 to 3 hours after oral administration under nonfasting conditions, independent of dose. Urinary recovery rate decreased with increasing doses. The maximum plasma concentration, half-life, and area under the concentration-time curve at the dose of 100 mg in nonfasting conditions were 3.78 μg/ml, 2.77 hours, and 25.51 μg·h/mL, respectively. S-1090 may be absorbed by both unsaturable passive and saturable active transport systems. During multiple dosing, the extent of absorption decreased slightly, but steady state was achieved within several days without changes in half-life. S-1090 binds to serum protein constantly, at a very high 97%, which might cause the long half-life of this drug. The high plasma concentration and long half-life of S-1090 are favorable for clinical use.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02355128
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  • 7
    Electronic Resource
    Electronic Resource
    Comparative electrophysiological effects of the antidepressants fluvoxamine and amitriptyline in the canine heart after myocardial infarction (1996)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 30-37 
    Details
    ISSN: 1432-1912
    Keywords: Fluvoxamine ; Amitriptyline Canine myocardial infarction ; Epicardial activation delay ; Arrhythmia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the effects of fluvoxamine and amitriptyline on epicardial activation delay of premature excitations, the effective refractory period, and the incidence of ventricular arrhythmias by programmed electrical ventricular stimulation in the canine heart after myocardial infarction. Additionally, we investigated whether the inhibition of norepinephrine reuptake by amitriptyline contributes to epicardial activation delay or arrhythmias by combination with propranolol pretreatment. Amitriptyline, at a dose of 3 mg/kg, significantly prolonged epicardial activation delay of premature excitations in the infarcted zone in a frequency-dependent manner (n = 10). Amitriptyline also prolonged epicardial activation delay of premature excitations in the normal zone (n = 10). The effective refractory period in the infarcted zone was significantly prolonged by amitriptyline at a dose of 3 mg/kg (n = 8). Amitriptyline increased the incidence of ventricular arrhythmias induced by programmed electrical ventricular stimulation (n = 8). Propranolol did not affect the epicardial activation delay caused by amitriptyline or the incidence of ventricular arrhythmias induced by programmed electrical ventricular stimulation (n = 6). Fluvoxamine, on the other hand, had no significant effect on epicardial activation delay of premature excitations (n = 10) or the effective refractory period (n = 8) in both the infarcted and normal zones. Fluvoxamine did not increase the incidence of ventricular arrhythmias induced by programmed electrical ventricular stimulation (n = 8). From the present results, fluvoxamine seems to have lower cardiac toxicity than amitriptyline. Moreover, the electrophysiological effects of amitriptyline in this model may be due to a direct cardiac depressive action, but not to the inhibition of norepinephrine reuptake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00168703
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  • 8
    Electronic Resource
    Electronic Resource
    Effects of DPI 201-106, a novel cardiotonic agent, on hemodynamics, cardiac electrophysiology and arrhythmias induced by programmed ventricular stimulation in dogs with subacute myocardial infarction: A comparative study with dobutamine (1991)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 344 (1991), S. 478-487 
    Details
    ISSN: 1432-1912
    Keywords: Positive inotropic agents ; DPI 201-106 ; Myocardial infarction ; Hemodynamics ; Ventricular tachycardia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary DPI 201-106 (DPI), a novel and potent cardiotonic agent, exhibits its effects by prolonging the open state of Na+ channels, resulting in an increase in action potential duration, and thus, is supposed to share the class III antiarrhythmic activity. The effects of DPI on the hemodynamics, intraventricular conduction and refractoriness of heart, and the incidence of arrhythmias induced by programmed electrical ventricular stimulation (PES) were compared with (±)-dobutamine. Dogs which survived for 5 to 7 days after the induction of myocardial infarction were used as the model. The presence of sub-acute myocardial infarction caused by occluding the left anterior descending coronary artery elicited a mild left ventricular dysfunction represented by a significant decrease in peak LV dp/dt by about 20%. Both i.v. bolus injection of DPI (1, 3 and 5 mg/kg) and i. v. continuous infusion of dobutamine (3, 5 and 10 μg/kg/min), which were administered in a cumulative manner, dose-dependently improved the hemodynamic parameters. At the higher doses of both DPI (3 and 5 mg/kg) and dobutamine (5 and 10 μg/kg/min) the control values were reached or even exceeded. DPI dose-dependently increased the effective refractory period (ERP) of both non-infarcted and infarcted ventricular myocardia to a similar degree, but the conduction time showed a frequency-dependent increase in the infarcted myocardium to a greater degree than in the non-infarcted myocardium after DPI. In contrast, dobutamine decreased the ERP in both non-infarcted and infarcted myocardia, and slightly increased the difference of refractoriness between the non-infarcted and infarcted zones with no effect on the intraventricular conduction. In the PES study, DPI (3 and 5 mg/kg) produced a significant decrease in the incidence of ventricular tachycardia, whereas dobutamine (5 and 10 μg/kg/min) tended to worsen the arrhythmias. These findings suggest that cardiotonic agents with a class III antiarrhythmic property such as DPI may be potentially useful for the management of heart failure accompanied by ischemic heart disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00172589
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  • 9
    Electronic Resource
    Electronic Resource
    Effects of bepridil and lidocaine on the intravenctricular conduction in acutely ischaemic and infarcted canine myocardium (1990)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 342 (1990), S. 683-690 
    Details
    ISSN: 1432-1912
    Keywords: Bepridil ; Lidocaine ; Intraventricular conduction ; ST-T alternans ; Myocardial ischaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Effects of bepridil, an antiarrhythmic and antianginal drug, on intraventricular conduction in acutely ischaemic and infarcted myocardium were examined in anaesthetized dogs, and compared with those of lidocaine. Bepridil at doses of 2 and 5 mg/kg markedly prolonged the conduction time of a premature excitation induced by a ventricular stimulation in the infarcted zone. The effect of bepridil was dependent on a coupling time of the stimulation. Bepridil showed a marked effect at a coupling time of 150 ms, while it showed no significant effect at a prolonged coupling time of 1 s. In other words, the effect of bepridil was interval-dependent. Lidocaine showed a similar interval-dependent effect, but the effect of lidocaine at a longer coupling time was less than that of bepridil. The premature stimulation produced severely delayed conduction which resulted in reentrant beats. Bepridil blocked these conductions, thereby preventing reentrant beats. In contrast to the depressant effect of bepridil in the infarcted myocardium, bepridil prevented the prolongation of conduction time during acute ischaemia. The alternation of the ST-T complex during acute ischaemia which is also an important arrhythmogenic factor was also attenuated by bepridil. Contrary to bepridil, lidocaine significantly enhanced the conduction delay and the alternation in the ST-T complex. In conclusion, bepridil as well as lidocaine showed an interval-dependent depression of the conduction in the infarcted zone of the heart, whereas during acute ischaemia bepridil in contrast to lidocaine attenuated the conduction delay and ST-T alternans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00175713
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  • 10
    Electronic Resource
    Electronic Resource
    Photochemically induced thrombosis of the rat coronary artery and functional evaluation of thrombus formation by occurrence of ventricular arrhythmias (1992)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 346 (1992), S. 550-554 
    Details
    ISSN: 1432-1912
    Keywords: Photochemical reaction ; Thrombosis ; Coronary artery ; Arrhythmia ; Thromboxane A2 synthetase inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During i. v. infusion of rose bengal (48 mg/kg/h), the proximal portion of the rat left coronary artery was illuminated from the outside of the myocardium by green light (540 nm) to produce a transluminal thrombus subsequent to endothelial damages. The primary endothelial damages within the illuminated vascular portion, which resulted from the photochemical reaction between the dye and green light, and the subsequent formation of transluminal platelet-rich thrombus, were easily revealed by both light and electron microscopy. The establishment of the thrombus was accompanied in all cases by the occurrence of ventricular arrhythmias due to myocardial ischaemia. The times required to initiate ventricular premature beats (VPBs) and ventricular tachycardia (VT) were 381 ± 96 s and 444 ± 114 s (mean ± SEM, n = 10), respectively. Pretreatment of the rat with acetylsalicylic acid (3 and 10 mg/kg, i. v.) before the initiation of illumination had no effect on the times required to exhibit the first VPBs and VT, the incidences of both types of arrhythmias were not reduced, and the thrombus was finally formed. On the other hand, pretreatment with Y-20811, a novel thromboxane A2 synthetase inhibitor (0.3, 1 and 3 mg/kg, i. v.), delayed the onset of both VPB and VT in a dose-dependent manner. The incidences of VPBs and VT were significantly reduced at 1 and 3 mg/kg, and the thrombus formation was prevented. The formation of a transluminal thrombus in the left coronary artery by the present technique was highly reproducible and could be functionally evaluated by the occurrence of ventricular arrhythmias.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169012
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