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  • 1
    Electronic Resource
    Electronic Resource
    Haemodynamic effects and pharmacokinetics of a new selective beta1-adrenoceptor agonist, prenalterol, and its interaction with metoprolol in man (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 9-13 
    Details
    ISSN: 1432-1041
    Keywords: prenalterol ; metoprolol ; haemodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effects of the selectiveβ 1-adrenoceptor agonist prenalterol were studied in healthy subjects before and after therapeutic doses of the selectiveβ 1-adrenoceptor blocker metoprolol. Plasma levels of the drugs were also determined in order to calculate certain pharmacokinetic variables. Intravenous infusion of prenalterol 0.13, 0.25 and 0.50 mg induced a dose-dependent decrease in total electromechanical systole (QA2) and pre-ejection period (PEP). The effect on left ventricular ejection time (LVET) was not significant. Increases in systolic blood pressure and heart rate were dose-dependent. Diastolic blood pressure did not change significantly. When metoprolol had been administered in a cumulative dose of 150 mg (mean maximal plasma level, 284 nmol/1) prenalterol had to be administered in doses that were twelve times higher than before theβ-blocker in order to induce the same haemodynamic effects. Prenalterol was rapidly distributed with an average half life of 8 min. This indicates that distribution equilibrium will be achieved within 30 min after intravenous administration. The overall elimination rate in the post-distributive phase corresponded to an average half life of 2.0 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563552
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetic studies in man of the selective beta1-adrenoceptor agonist, prenalterol (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 91-97 
    Details
    ISSN: 1432-1041
    Keywords: prenalterol ; pharmacokinetics ; oral administration ; i. v. administration ; 3H-prenalterol ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of prenalterol, a selective β1-adrenoceptor agonist, has been studied in healthy subjects, by following the plasma concentration and urinary excretion of the unchanged compound and its total radioactive metabolites after oral and intravenous administration. Each of six healthy subjects received a single i. v. dose (2.5 mg) and three oral doses (2.5, 5.0 and 10 mg) of prenalterol. The oral dose was administered as a solution. Three of the subjects received the intravenous and oral doses of 2.5 mg as tritiated drug. Prenalterol was rapidly and completely absorbed after oral administration. The peak plasma concentration was attained after about 0.5 h. About 25% of prenalterol reached the systemic circulation. Prenalterol was extensively distributed to extravascular tissues with a half-life of the distribution phase close to 7 min. About 90% of the dose was excreted in urine within 24 h irrespective of the route of administration, indicating complete absorption of the drug. On average 60% of the i. v. and 13% of the oral doses were excreted as unchanged drug. The elimination half-life of the compound was 1.8 h, and the decline in the plasma concentration of the metabolites indicated a slower elimination rate than for the unchanged drug. Dose-dependent kinetics were not observed after the oral doses examined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607143
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  • 3
    Electronic Resource
    Electronic Resource
    Acute effects of felodipine and nifedipine on hepatic and forearm blood flow in healthy men (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 529-533 
    Details
    ISSN: 1432-1041
    Keywords: felodipine ; nifedipine ; calcium antagonists ; hepatic blood flow ; forearm blood flow ; healthy volunteers ; haemodynamic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute effects of oral administration of felodipine 10 mg and nifedipine 10 mg on heart rate, blood pressure, forearm blood flow and hepatic blood flow were studied in nine healthy men. Both drugs caused an increase in heart rate of 16 and 7 beats · min−1, respectively. Hepatic blood flow was significantly increased by 1.2 and 0.41 · min−1 after felodipine and nifedipine. There was also a decrease in diastolic blood pressure, 10 and 5 mm Hg, respectively, after felodipine and nifedipine. The forearm blood flow was increased by about 30 ml · 100 ml−1 · min−1 after felodipine, but nifedipine had no effect. The haemodynamic effects were most pronounced 50 min after drug administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278576
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  • 4
    Electronic Resource
    Electronic Resource
    Haemodynamic effects and pharmacokinetics of felodipine at rest and during exercise in hypertensive patients treated with metoprolol or atenolol (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 459-465 
    Details
    ISSN: 1432-1041
    Keywords: felodipine ; metoprolol ; atenolol ; hypertension ; exercise ; pharmacokinetics ; adverse effects ; hypotensive action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A study has been performed in thirteen patients with essential hypertension, WHO Class I–II, and a diastolic blood pressure ≥95 mm Hg, on beta-blocker (metoprolol or atenolol) monotherapy, who were also given felodipine 10 mg b.d. for 28 days. The acute and steady state blood pressure response at rest and during exercise, and the pharmacokinetics of felodipine and metoprolol, were examined. Felodipine in combination with the beta-blocker reduced the systolic and diastolic blood pressures acutely and at steady-state. The duration of the effect was longer at steady-state. There was a significant correlation between the plasma concentration of felodipine and the change in blood pressure. The increase in systolic blood pressure during exercise was of the same magnitude before and after felodipine administration. No change in resting supine heart rate was found after the administration of felodipine. There were no significant differences in the pharmacokinetics of felodipine during long-term treatment, except for the trough plasma concentration, which was increased at steady-state, even though cumulation of felodipine and its metabolite did not occur. There was a significant decrease in the maximal plasma concentration and AUC of metoprolol after 28 days of treatment with felodipine, but its elimination half-life was not changed. The adverse reactions reported during this study were those generally seen after dihydropyridines and, except for two patients who were withdrawn after the first study day, the effects were well tolerated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558124
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  • 5
    Electronic Resource
    Electronic Resource
    The acute haemodynamic and renal effects of oral felodipine and ramipril in healthy subjects (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 327-332 
    Details
    ISSN: 1432-1041
    Keywords: Felodipine ; ramipril ; haemodynamic effects ; renal function ; healthy subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The aim of the present investigation was to compare the acute haemodynamic and renal effects of the calcium antagonist felodipine with the ACE inhibitor ramipril and with placebo. Single oral doses of felodipine 5 and 20 mg, ramipril 2.5 and 10 mg, and placebo were given to ten healthy subjects in a double-blind cross-over study. Blood pressure, heart rate, forearm blood flow (FBF), forearm vascular resistance (FVR), renal blood flow (RBF), renal vascular resistance (RVR), glomerular filtration rate (GFR), filtration fraction (FF), diuresis, and sodium excretion were recorded for 4.75 h after administration. Felodipine 20 mg caused a significant fall in diastolic blood pressure, maximal 12 % compared with placebo, while there were no significant effects of felodipine 5 mg or the two doses of ramipril. Heart rate increased significantly after both doses of felodipine, maximal 28% after the 20 mg dose. There was also a small but significant increase in heart rate of 12% after ramipril 2.5 mg. FVR fell significantly after both doses of felodipine, maximal 38 % after the 20 mg dose. There were no significant changes in FVR after any of the ramipril doses. Both doses of felodipine and both doses of ramipril caused significant reductions in RVR. Maximal reduction, 33 %, was found after felodipine 20 mg. There were no significant changes in GFR or FF with either drug. Felodipine caused a significant increase in natriuresis, maximal 129% while ramipril did not.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265949
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  • 6
    Electronic Resource
    Electronic Resource
    Haemodynamic and tolerance studies in man of a new, orally active, selectiveβ 1-adrenoceptor agonist H 80/62 (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 163-170 
    Details
    ISSN: 1432-1041
    Keywords: H 80/62 ; haemodynamic effects ; noninvasive techniques ; selectivity ; β1-adrenoceptor agonist ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The selective β1-adrenoceptor agonist H 80/62 was administered intravenously and orally to healthy subjects and its effects on systolic time intervals, arterial blood pressure and heart rate were studied. Side-effects were noted too, and continuous ECG-recordings were made in order to study its arrhythmogenic effect. After i.v. administration of H 80/62 20 µg/kg body weight there was shortening of total electromechanical systole, the pre-ejection period and of the left ventricular ejection time, systolic blood pressure tended to increase, and diastolic blood pressure and heart rate were essentially unchanged. When administered orally as a sustained-release preparation in doses between 20 and 40 mg the haemodynamic effects were qualitatively the same as after i.v. administration, but in some studies there was a slight increase in heart rate. During exercise the systolic blood pressure and heart rate were identical after H 80/62 and placebo. The effect of the drug was maximal immediately after cessation of the i.v. infusion and basal values were regained within 60 min. After oral administration of a sustained-release formulation the effect was maximal after one hour and persisted for at least five to seven hours. The drug was well tolerated on repeated administration. The incidence of ventricular extrasystoles was possibly increased in one subject out of eight (11 ventricular extrasystoles during 18 h). The results of this Phase I study of H 80/62 warrant further evaluation of the drug in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609978
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  • 7
    Electronic Resource
    Electronic Resource
    Metabolic and haemodynamic effects and pharmacokinetics of a new selective beta1-adrenoceptor agonist, prenalterol, in man (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 81-86 
    Details
    ISSN: 1432-1041
    Keywords: prenalterol ; beta1-adrenoceptor agonist ; metabolic effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The metabolic and haemodynamic effects of three intravenous doses (0.5, 1.0 and 4.0 mg) of prenalterol, a selective β1-adrenoceptor agonist, were studied in 10 healthy male subjects. Plasma levels of prenalterol during the experiments were related to the haemodynamic effects. Prenalterol induced a dose-dependent increase in systolic blood pressure and heart rate. The maximal effects amounted to about 30 mm Hg and 15 beats/min, respectively, after the highest dose (4.0 mg). The diastolic blood pressure fell by a maximum of about 15 mm Hg. The effect of prenalterol on systolic blood pressure and heart rate persisted for about 3 h after the end of the last infusion, whereas that on diastolic blood pressure only lasted for 60 min. Compared with placebo, there was a moderate increase in plasma FFA and glycerol. A small rise in insulin level was also recorded, but no significant change was seen in other metabolic variables — triglycerides, glucose, lactate, pyruvate. Serum potassium tended to decrease and serum sodium was unchanged. The initial distribution of prenalterol was rapid (half-life 7 min) and the overall elimination rate corresponded to a plasma half-life of 2 h. A linear relationship was found between the plasma level of prenalterol and its effects on systolic blood pressure and heart rate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562614
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  • 8
    Electronic Resource
    Electronic Resource
    Non-genetic reactivation of differently inactivated vaccinia virus (1970)
    Springer
    Archives of virology 32 (1970), S. 291-298 
    Details
    ISSN: 1432-8798
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The non-genetic reactivation of vaccinia virus was studied in cultures of GMK cells. Different methods for obtaining reactivating and reactivable virus have been tested. Besides the heat-treatment, treatment with urea, flufenamic acid, indomethacin, PCMB, HgCl2 or iodoacetamid were all found to produce reactivable virus. N-mustard treatment was the only method tested which produced reactivating virus. Neither soluble vaccinial antigens nor antigens from mechanically disintegrated virions were able to cause reactivation of reactivable virus. Kinetic studies showed that the reactivation is about 10 times more dependent upon the dosage of the reactivating virus than of the reactivable one. Furthermore, the intracellular life-time of the components for reactivation was studied. It was found that the reactivable component of heat-treated virions remained intracellularly in a functional form for the longer period, about three days, whereas the reactivating component of N-mustard treated virus lost the specific function after only about one day.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01250056
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