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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 51 (1997), S. 379-384 
    ISSN: 1432-1041
    Schlagwort(e): Key words Nebivolol ; β-adrenoceptor blockers ; β1-selectivity ; pharmacological properties
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Objectives: The aims of the present study were to determine (1) the β1-blocking potency and (2) the β1-adrenoceptor selectivity of nebivolol in man after repeated dosing (7 days) compared with that after a single oral intake and with that after atenolol for 7 days. In addition, it was investigated whether (3) nebivolol has α1-blocking properties which might at least in part explain the vasodilating property of the compound. Methods: Twelve healthy subjects were randomized in an open, two-way cross-over study. β1-Blocking potency and β1-adrenoceptor selectivity of nebivolol 5 mg once daily (o.d.) were compared with those of atenolol at three doses (25, 50 and 100 mg) o.d. Measurements were performed after 1 and 7 days of drug intake. β1-Adrenoceptor potency was assessed by the percentage decrease in exercise-induced tachycardia (ΔEIT) during β-blockade. β1-Selectivity of nebivolol and atenolol were investigated using the heart rate response to isoprenaline at equipotent β1-blocking dosages of both drugs. α1-Blockade of nebivolol was measured using the phenylephrine dose-response test. Results: ΔEIT after a single oral dose of nebivolol 5 mg (10%) was significantly smaller than after nebivolol 5 mg o.d. for 7 days (15%). After 1 week of treatment no difference was seen in ΔEIT between nebivolol 5 mg o.d. and atenolol 25 mg o.d. (16%). At these dosages the suppression in isoprenaline-induced tachycardia by both drugs did not differ (CD20 ratio 1.7). In contrast to atenolol 25 mg, after 1 week of nebivolol 5 mg o.d., blood pressure decreased. This decrease averaged 10% and – like in a study with hypertensive patients – was similar with that after atenolol 100 mg o.d. None of the phenylephrine test parameters changed from pre-study values after nebivolol. Conclusions: β1-Blockade of nebivolol 5 mg is larger after repeated dosing than after a single oral intake. After once daily repeated dosing nebivolol 5 mg and atenolol 25 mg are equipotent in β1-antagonism. No difference in β1-selectivity is observed between the two drugs. Nebivolol has no additional α1-blocking property, which may at least in part explain its vasodilating effect.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 45 (1993), S. 101-105 
    ISSN: 1432-1041
    Schlagwort(e): Lipolysis ; Propranolol ; beta-blockade ; endurance exercise ; glycerol ; NEFA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Inhibition of adipose tissue lipolysis may be involved in the impairment of endurance capacity after administration of a β-adrenoceptor blocker. During endurance exercise, no significant decrease in plasma glycerol and free fatty acid (NEFA) concentrations after β-adrenoceptor blockade is found. However, the levels during recovery from exhaustion are lower after β-adrenoceptor blockade. This study was designed to investigate whether the lower levels after exercise are due to β-adrenoceptor blockade or to the shorter time to exhaustion after administration of a β-adrenoceptor blocker. In a single-blind study, 11 well-trained male subjects (age 23 (0.9) y) performed a cycle ergometer test at 70% Wmax until exhaustion 2 h after intake of 80 mg propranolol. One week later, the test was repeated after intake of placebo and was stopped at the time of exhaustion in the previous test. Average exercise time was 24 min. During exercise plasma glucose was lower, whereas plasma lactate and the respiratory exchange ratio were significantly higher when the subjects were on propranolol. Glycerol and NEFA concentrations during exercise were not significantly different between the two conditions. Despite an identical exercise time, glycerol and NEFA concentrations during recovery were significantly lower after propranol treatment. In conclusion, lipolysis is inhibited during exercise after propranolol, probably causing a shift from fat to carbohydrate combustion.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1432-1041
    Schlagwort(e): Hypercholesterolaemia ; HMG-CoA-reductase inhibitors ; Pravastatin ; vessel wall properties ; arterial distensibility ; arterial compliance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Hypercholesterolaemia is a risk factor for atherosclerosis and induces endothelial dysfunction. Endothelial dysfunction may increase vascular tone and arterial stiffness and as a consequence may decrease arterial distensibility (DC) and arterial compliance (CC). It is hypothesized that lipid-lowering therapy may enhance DC and CC. Therefore, the present study investigates the effect of lipid-lowering therapy with pravastatin on the haemodynamics, DC and CC of the elastic common carotid artery (CCA), and the muscular femoral (FA) and brachial (BA) arteries in patients with primary hypercholesterolaemia. After an 8-week placebo run-in period with a low-cholesterol diet, 19 patients with total cholesterol concentrations of between 6.5 and 9.0 mmol·l−1 and triglyceride concentrations 〈4 mmol·l−1 entered a double-blind placebo controlled crossover study. Patients received pravastatin 40 mg o.d. or placebo, each for 8 weeks. Throughout the study the lipid-lowering diet was continued. With pravastatin, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides were decreased (total cholesterol 26%, LDL-C 35%, triglycerides 16%), while high-density lipoprotein cholesterol (HDL-C) was not changed. Other laboratory values remained within the normal range. Blood pressure, heart rate, cardiac function and systemic vascular resistance were not influenced by pravastatin. Compared to placebo, diameter, distensibility and compliance of all arteries were not statistically significantly changed with pravastatin. These data suggest that, in patients with mild to moderate primary hypercholesterolaemia, short-term lowering of plasma cholesterol does not alter the haemodynamics and vessel wall properties of large arteries.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 36 (1989), S. 467-471 
    ISSN: 1432-1041
    Schlagwort(e): nitrendipine ; renal failure ; pharmacokinetics ; protein binding
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and plasma protein binding of nitrendipine in patients with terminal renal failure have been compared with those in subjects with normal renal function. Kinetic parameters were calculated after a single 40 mg oral dose, an i.v. injection of 3 mg and after a 15 mg i.v. infusion of nitrendipine. Steady-state plasma levels were determined after 5 days of oral treatment with 20 mg b.d. Pharmacokinetic parameters and steady-state plasma levels in patients with renal failure did not differ from those in subjects with normal renal function. Nitrendipine was as highly bound to plasma proteins in patients with renal failure, as in subjects with normal renal function. The plasma protein did not differ between the two. The dosage of nitrendipine need not be modified for kinetic reasons in patients with renal failure.
    Materialart: Digitale Medien
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  • 5
    ISSN: 1432-1041
    Schlagwort(e): ANP ; verapamil ; hypertension ; age
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a double-blind, placebo-controlled crossover study, the plasma atrial natriuretic peptide (ANP) levels of nine young and ten elderly hypertensive patients were compared after placebo and after treatment with 120 mg verapamil given three times daily over 4 weeks. During placebo, plasma ANP levels proved to be higher in elderly patients than in young subjects. Chronic treatment with verapamil induced a rise in ANP levels in both young and elderly patients with hypertension.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 37 (1989), S. 185-189 
    ISSN: 1432-1041
    Schlagwort(e): nifedipine ; renal failure ; pharmacokinetics ; protein binding ; blood pressure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The total and free steady-state plasma levels of nifedipine in patients with renal failure have been compared with those in subjects with normal renal function. Studies were done after administration of nifedipine 10 mg t.d.s. p.o. for 5 days, after i.v. infusion of 4·4 mg, and after a single 10 mg oral dose. The systemic clearance of nifedipine after a single i.v.-dose was higher in subjects with renal insufficiency (854 ml/min) than in those with normal renal function (468 ml/min). After the single oral dose the AUC (6100 ng·min·ml−1) and maximum plasma concentration (75.0 ng·ml−1) were lower than in subjects with normal renal function (19300 ng·ml−1; 122 ng·ml−1). The plasma protein binding of nifedipine averaged 95.5% in normal subjects and 94.8% in patients with renal failure. Although free and total steady-state plasma levels of nifedipine tended to be somewhat lower than normal in renal failure, the changes in pharmacokinetics and decreased protein binding of nifedipine did not result in a significantly different steady-state plasma level of the drug. The blood pressure response to a given plasma nifedipine level appeared to be enhanced in renal failure.
    Materialart: Digitale Medien
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  • 7
    ISSN: 1573-739X
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 8
    ISSN: 1573-739X
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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