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  • Articles  (90)
  • healthy volunteers  (90)
  • Springer  (90)
  • American Institute of Physics
  • Nature Publishing Group
  • 1990-1994  (90)
  • Medicine  (90)
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  • Articles  (90)
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  • Springer  (90)
  • American Institute of Physics
  • Nature Publishing Group
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  • 1
    Electronic Resource
    Electronic Resource
    A comparison of the effects of fluvoxamine and amitriptyline on autonomic functions in healthy volunteers (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 529-533 
    Details
    ISSN: 1432-1041
    Keywords: Fluvoxamine ; Amitriptyline ; antidepressants ; cholinergic functions ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have compared the effects of single oral doses of fluvoxamine (50 mg and 100 mg), amitriptyline (50 mg and 100 mg), and placebo on some autonomic functions in ten healthy volunteers, using a balanced, double-blind, crossover design. Amitriptyline significantly reduced salivation, the miosis evoked by locally applied pilocarpine, and the sweat secretion evoked by locally applied carbachol. Fluvoxamine also significantly attenuated carbachol-evoked sweat gland activity, although to a smaller degree than amitriptyline; fluvoxamine did not significantly alter salivation or pilocarpine-evoked miosis. Neither treatment significantly altered the miotic responses evoked by brief light stimuli. Heart rate and blood pressure were not greatly affected by either treatment, although the fall in heart rate (erect posture) with placebo was significantly reduced by amitriptyline (100 mg). The results suggest that fluvoxamine has some antimuscarinic activity in man, but is considerably less potent in this respect than amitriptyline.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314863
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  • 2
    Electronic Resource
    Electronic Resource
    The effect of exercise on atropine pharmacokinetics (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 395-397 
    Details
    ISSN: 1432-1041
    Keywords: atropine ; exercise ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven healthy males (19–32 y) underwent each of four separate conditions in a repeated measures design. Five of these subjects underwent an additional trial. In four of five trials subjects received 2.0 mg atropine sulfate intramuscularly in the anterolateral portion of the left thigh: at rest (T1); following completion of a single exercise (Ex) bout (T2), (Each bout consisted of 25 min of stationary cycling at 40% VO2 max with 5 min of seated rest), prior to three Ex bouts (T3) and following one and prior to three Ex bouts (T5). Trial 4 (T4) was the same as T3 with the substitution of a saline placebo. Serum samples were collected over a 12 h period and atropine concentration was determined by RIA. Ex trials were compared to T1. Ex prior to atropine (T2) significantly decreased the mean volume of distribution (Vz, 278 vs 2321). Ex in T3 significantly decreased the serum half life (t1/2, 4.2 vs 3.5 h), Vz (278 vs 1981), and clearance (CL, 763 vs 638 ml·min−1) and significantly increased the peak concentration (Cp, 6.7 vs 12.3 ng·ml−1) and area under the curve (AUC, 44.1 vs 53.1 ng·ml−1). In T5, Ex significantly decreased the t1/2 (3.4 h), Vz (182 l) and CL (575 ml·min−1) and significantly increased the absorption rate constant (ka, 0.482 vs 1.1 min−1), elimination rate constant (ke, 0.0012 vs 0.0015 min−1), Cp (14 ng·ml−1) and AUC (53.3 ng·h·ml−1). These results demonstrate that moderate Ex either prior to and/or immediately following drug administration has the capacity to significantly modify atropine pharmacokinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315417
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  • 3
    Electronic Resource
    Electronic Resource
    Comparative antidotal efficacy of activated charcoal tablets, capsules and suspension in healthy volunteers (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 501-505 
    Details
    ISSN: 1432-1041
    Keywords: activated charcoal ; antidotal efficacy ; healthy volunteers ; formulation ; paracetamol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The efficacy of several formulations of activated charcoal (AC) was compared by measuring the intestinal absorption of a solution of 1 g paracetamol administered 2 min before administration of 5 g AC as suspension (200 ml), tablets (40 of 125 mg) or capsules (25 of 200 mg). The suspension medium without AC was used as the control treatment. Based on the results of a pilot experiment, an 8 subject panel was used in a two 4×4 Latin square design. All treatments with AC resulted in a statistically significant decrease in paracetamol absorption compared to the control treatment. The suspension was considerably and significantly more effective than the tablets or capsules. Treatment with tablets was slightly but significantly more effective than capsules. The intake of large numbers of tablets and capsules was difficult. In the hospital AC suspensions are available. For first aid elsewhere, at home, at the working place or in the general practitioner's surgery a preservable and easily redispersible AC formulation would be preferable to the present solid forms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280944
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  • 4
    Electronic Resource
    Electronic Resource
    Endoscopic evaluation of the effect of ketoprofen, ibuprofen and aspirin on the gastroduodenal mucosa (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 685-687 
    Details
    ISSN: 1432-1041
    Keywords: NSAID ; Gastrotoxicity ; gastroscopy ; healthy volunteers ; ibuprofen ; ketoprofen ; aspirin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Endoscopic lesions of the gastric mucosa were evaluated in 12 healthy volunteers after administration of single doses of ketoprofen (25 mg), ibuprofen (200 mg) and aspirin (500 mg) in a randomized, double-blind, crossover study. The grades of the lesions (according to Lanza's scale) were lower after the administration of ketoprofen than aspirin and were comparable to ibuprofen. An endoscopic score 〉1 was observed in 3 cases after ibuprofen or ketoprofen, and in 8 cases after aspirin. At a time when low, single doses of NSAIDs are widely used as analgesics, gastroscopy makes it possible directly to assess the local agressivity of these molecules. In this way it was possible to demonstrate that the local toxicity of NSAIDs was lower than that of aspirin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265938
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  • 5
    Electronic Resource
    Electronic Resource
    Effect of magnesium hydroxide on the absorption and efficacy of tolbutamide and chlorpropamide (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 675-679 
    Details
    ISSN: 1432-1041
    Keywords: Tolbutamide ; Magnesium hydroxide ; chlorpropamide ; gastrointestinal absorption ; drug interaction ; healthy volunteers ; plasma glucose ; plasma insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of magnesium hydroxide on the absorption and efficacy of tolbutamide and chlorpropamide was examined in a total of 32 healthy volunteers in two separate, randomized parallel-group studies, with 16 subjects in each study. After an overnight fast, the first group of 8 volunteers ingested 500 mg tolbutamide or 250 mg chlorpropamide with 150 ml water, and the second group the same doses of the active drugs with 150 ml water containing 850 mg magnesium hydroxide. Magnesium hydroxide increased the area under the plasma tolbutamide concentration-time curve (AUC) from 0 to 1 h and from 0 to 2 h by 5-fold and 2.5-fold, respectively. The peak plasma concentration, peak time and total AUC were not significantly altered. The incremental insulin area and the decremental glucose area from 0 to 1.5 h were significantly larger in the magnesium hydroxide group than in the controls. The maximum insulin response to tolbutamide was increased fourfold by coadministration of magnesium hydroxide, and it occurred about 1 h earlier than in the control group. In addition, the maximum fall in plasma glucose concentration was attained about 1 h earlier in the antacid group. A tendency to an increased rate of chlorpropamide absorption was observed after magnesium hydroxide, but it did not appear to affect the insulin and glucose responses to chlorpropamide. It is concluded that magnesium hydroxide increased the early bioavailability of tolbutamide, resulting in enhanced insulin and glucose responses. A tendency toward accelerated chlorpropamide absorption by magnesium hydroxide was also observed, but the efficacy of chlorpropamide was unaffected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265936
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  • 6
    Electronic Resource
    Electronic Resource
    Absolute bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin from different regions of the gastrointestinal tract in man (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 473-476 
    Details
    ISSN: 1432-1041
    Keywords: dDAVP ; bioavailability ; gastrointestinal tract ; healthy volunteers ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absolute bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP) from different regions of the gastrointestinal (GI) tract (stomach, duodenum, jejunum, ileum, colon, rectum) has been studied in 6 healthy, male volunteers aged 24 to 35 years, followed for 12 h after each drug administration. For i. v. administration the subjects received 4 μg dDAVP. For intestinal administration 400 μg dDAVP was directly applied to six distinct sites in the GI tract via two or four channel tubes with or without a distal occlusive balloon. Biological effects were assessed and plasma and urinary levels of dDAVP were measured using a specific, sensitive RIA. Urine osmolality remained elevated and diuresis decreased for 12 h following dDAVP administration irrespective of the site of application. After i. v. administration, the half-life of elimination of dDAVP was 60.0 min, plasma clearance 1.7 ml·min−1·kg−1, amount excreted in urine 2.0 μg and renal clearance was 0.8 ml·min−1·kg−1. The mean bioavailability (f) after gastric application was 0.19% (range 0.02–0.35%). f was 0.24% after duodenal application (range 0.04–0.62%), 0.19% after jejunal (range 0.01–0.41%), 0.03% after distal ileal (range 0.01–0.08%), 0.04% after proximal colonic (range 0.01–0.12%) and 0.04% after rectal (0.01–0.10%) application. The bioavailability was significantly higher in the three upper GI regions in comparison to the three lower regions. The bioavailability of dDAVP after gastric, duodenal and jejunal application was similar to that after swallowing a tablet in a previous study. Absorption from the ileum was lower than expected and no preferential site of absorption was found.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315546
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  • 7
    Electronic Resource
    Electronic Resource
    Differential cardiovascular effects of propranolol, atenolol, and pindolol measured by impedance cardiography (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 47-53 
    Details
    ISSN: 1432-1041
    Keywords: Atenolol ; Propranolol ; Pindolol ; transthoracic electrical bioimpedance ; cardiac output ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have evaluated Sramek's method of impedance cardiography as a non-invasive way of detecting the cardiovascular effects of drugs. We made cardiovascular measurements using the method during passive tilting and exercise 2 h after the oral administration of atenolol (50 and 100 mg), propranolol (40 and 80 mg), pindolol (5 and 10 mg), and placebo in seven separate studies involving eight healthy male volunteers. Equivalent doses of the pure antagonists atenolol (β1) and propranolol (β1, β2) produced similar reductions in heart rate, systolic blood pressure, and cardiac index, and increases in stroke volume and total peripheral resistance, particularly during exercise. In contrast the partial agonist pindolol produced increases in heart rate and cardiac index, and reductions in peripheral resistance at rest. During passive tilting and exercise pindolol reduced heart rate, but cardiac output and total peripheral resistance were unchanged except at the highest levels of exercise. The similar cardiovascular effects of atenolol and propranolol, but differing effects of pindolol, are consistent with reports using other methods of measurement. This suggests that impedance cardiography may have a place in the non-invasive assessment of the cardiovascular effects of drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314919
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  • 8
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and pharmacodynamics of ramipril and piretanide administered alone and in combination (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 545-550 
    Details
    ISSN: 1432-1041
    Keywords: Ramipril ; Piretanide ; pharmacokinetics ; pharmacodynamics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and pharmacodynamics of single oral doses of 5 mg ramipril and 6 mg piretanide administered separately and in combination were determined in a single blind, randomised, 3-period cross-over study in 24 healthy male volunteers. The peak plasma concentrations of ramipril and ramiprilat increased slightly (from 11.9 to 14.8 ng/ml, and from 6.39 to 8.96 ng/ml, respectively) as did the area under the plasma concentration-time curve of ramipril (0–4 h) and ramiprilat (0–24 h) (from 15.8 to 19.8 ng·ml−1·h, and from 63.4 to 74.6 ng·ml−1·h, respectively). The urinary excretion of ramiprilat also rose (from 6.82 to 7.73 % of dose) following simultaneous treatment with piretanide. These effects were probably due to reduced first-pass metabolism of ramipril/ramiprilat to inactive metabolites. The blood pressure lowering effect, the time course of inhibition of ACE activity in plasma and the concentration-response relationship for the inhibition of plasma ACE activity were not affected by piretanide. The peak plasma concentration of piretanide was somewhat reduced (from 285 to 244 ng/ml) following simultaneous treatment with ramipril. No other pharmacokinetic parameter was affected. Piretanide increased urine flow, and sodium, chloride and potassium excretion, especially during the first 2 hours following administration. These pharmacodynamic parameters were not affected by ramipril. Thus, simultaneous administration of single oral doses of ramipril and piretanide caused modest changes in the peak and average plasma concentrations of both drugs, which did not lead to detectable alterations in the pharmacodynamic parameters measured in healthy volunteers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00196113
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  • 9
    Electronic Resource
    Electronic Resource
    Insulin concentrations and insulin sensitivity after short-term amiloride in healthy subjects (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 469-472 
    Details
    ISSN: 1432-1041
    Keywords: Amiloride ; Insulin sensitivity ; hyperinsulinemic euglycemic clamp ; glucose utilization ; glucose production ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We have evaluated the short-term effects of amiloride on insulin action in vivo, since amiloride is known to impair insulin action in vitro. Seven healthy subjects were treated according to a randomized, double-blind, cross-over protocol. The treatment periods were 3 days each with amiloride 15 mg daily and placebo. Insulin action on glucose turnover was assessed directly after each treatment period with the hyper-insulinaemic euglycaemic glucose clamp technique. At the two insulin concentrations studied (∼ 30 mU·l−1 and ∼ 200 mU·l−1), the glucose infusion rate required to maintain constant euglycaemia did not differ after either amiloride or placebo. The rates of glucose production and utilization were also similar, whereas the so-called insulin sensitivity index at the lower insulin concentration was significantly reduced (by about 15 %) after amiloride. Moreover, amiloride produced significantly higher fasting insulin and C-peptide concentrations, whereas fasting glucose and NEFA concentrations were unaltered. In conclusion, these data suggest that short-term amiloride slightly impairs insulin sensitivity with respect to glucose uptake. However, overall glucose homoeostasis does not appear to be affected, probably due to a compensatory rise in plasma insulin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00191913
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  • 10
    Electronic Resource
    Electronic Resource
    Comparison of the effects of dilevalol and propranolol on systemic and regional haemodynamics in healthy volunteers at rest and during exercise (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 39-47 
    Details
    ISSN: 1432-1041
    Keywords: Dilevalol ; Propranolol ; intrinsic sympathomimetic activity ; healthy volunteers ; pulsed Doppler ; regional haemodynamics ; plasma renin activity ; plasma atrial natriuretic factor ; plasma norepinephrine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effects of single oral doses of dilevalol 400 mg and propranolol 80 mg on systemic and regional haemodynamics at rest and after sub-maximal exercise, were compared, in a placebo-controlled, randomised, double-blind, crossover study in 6 healthy male volunteers. At rest, as compared to placebo, neither dilevalol nor propranolol significantly affected arterial pressure and heart rate but, whereas propranolol decreased cardiac output (−27% at 2 h) and tended to increase total peripheral resistance, dilevalol tended to increase cardiac output and decreased total peripheral resistance (−7% at 2 h). Neither dilevalol nor propranolol affected brachial artery diameter. Propranolol tended to decrease brachial artery flow (−20% at 2 h) and to increase brachial vascular resistance (+25% at 2 h), but dilevalol did not and the brachial irrigation ratios did not change. Neither of the drugs affected carotid haemodynamics or plasma atrial natriuretic factor. Both drugs tended to decrease plasma renin activity, and dilevalol (+82% at 2 h) increased norepinephrine more than propranolol (+19% at 2 h). After exercise, dilevalol and propranolol produced similar falls in the induced increases in arterial pressure, heart rate and cardiac output, and had the same effects on regional haemodynamics, plasma renin activity and atrial natriuretic factor. Finally, dilevalol greatly increased plasma norepinephrine. We conclude that the β2-adrenoceptor agonist activity of dilevalol was clearly expressed at rest, thus inducing vasodilation and counteracting the β-adrenoceptor blockade-induced negative chronotropic and inotropic effects. However, during sub-maximal exercise, only the β-adrenoceptor antagonist activity of dilevalol was apparent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193476
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