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  • man  (9)
  • Springer  (9)
  • Oxford University Press
  • PANGAEA
  • 1975-1979  (9)
  • 1935-1939
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  • Springer  (9)
  • Oxford University Press
  • PANGAEA
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Year
  • 1
    Electronic Resource
    Electronic Resource
    Correlation between increased dopamine-β- hydroxylase activity and catecholamine concentration in plasma: Determination of acute changes in sympathetic activity in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 181-188 
    Details
    ISSN: 1432-1041
    Keywords: Sympathetic activity ; plasma catecholamine concentration ; dopamine-β-hydroxylase activity ; graded physical exercise ; heart rate ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 11 healthy untrained volunteers the increase in plasma dopamine-β-hydroxylase (DBH) activity during graded physical exercise has been examined as a true measure of increased activity of the sympathetic nervous system. The correlation between DBH activity, catecholamine concentration (CA) in plasma and heart rate was studied. When work on an electrically braked bicycle ergometer was gradually increased from 12.5 to 100, 200 and 300 watts there was a linear increase in DBH activity and heart rate; the increase in CA concentrations followed an exponential function. The peak values for DBH activity and CA concentration in plasma after the 300 watt work load (as percentages of the resting levels) were 130±3% and 820±71%, respectively; the adrenaline concentration in plasma increased only to 150±19% (p〉0.05). There were significant correlations between heart rate and work load, DBH and work load and log CA and work load. The data imply direct correlations between heart rate and DBH, heart rate and log CA and DBH and log CA. The exponential increase in noradrenaline concentration in plasma might be due either to a greater net “overflow” from sympathetic nerve endings, and/or to increased secretion by the adrenal medulla. In the latter case, the release of noradrenaline would not be accompanied by secretion either of adrenaline or DBH. After work ceased there were sharp falls in heart rate and CA concentration, which indicate an immediate drop in sympathetic activity. DBH activity in plasma returned to normal very slowly; it reached half maximum values after 20 – 22 min. It is concluded that increased sympathetic activity in man can be estimated in vivo as changes in DBH and/or CA concentration in plasma. In contrast, a rapid decrease in sympathetic activity is directly reflected only by a rapid fall in the plasma concentrations of CA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567112
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  • 2
    Electronic Resource
    Electronic Resource
    Excretion of norephedrine by man after oral administration of oxyfedrine (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 161-166 
    Details
    ISSN: 1432-1041
    Keywords: Oxyfedrine ; norephedrine ; man ; urinary excretion ; sympathomimetic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After oral administration of oxyfedrine to healthy volunteers, norephedrine was identified in the urine by thin layer chromatography and gas liquid chromatography and mass spectrography. 30 hours after single oral doses of 8, 16 or 24 mg of oxyfedrine, about 4, 8 and 9 mg, respectively, of norephedrine were found in the urine, i.e. on a molar base 75–100% of the dose was excreted as norephedrine. The peak of excretion occurred within 2–4 hours after administration of the drug. No accumulation of oxyfedrine and/or its metabolite was observed after administration of 16 mg of oxyfedrine t.i.d. for three days. It could not be decided whether oxyfedrine was metabolized to norephedrine by liver enzymes, as in rats, or was spontaneously degraded to norephedrine, e.g. in duodenal fluid before absorption. 30–150 min after oral oxyfedrine (24 mg) norephedrine was demonstrable in duodenal fluid. Thus, in addition to the directβ-sympathomimetic effects of oxyfedrine, it may also have indirect sympathomimetic effects because of the noradrenaline-releasing properties of its metabolite norephedrine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567109
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  • 3
    Electronic Resource
    Electronic Resource
    Induction of drug metabolism in man after rifampicin treatment measured by increased hexobarbital and tolbutamide clearance (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 219-227 
    Details
    ISSN: 1432-1041
    Keywords: Rifampicin ; induction of drug metabolism ; hexobarbital kinetics ; tolbutamide kinetics ; plasma concentrations ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five healthy volunteers took 1.2 g rifampicin daily for 8 days, and before and afterwards each received hexobarbital (7.32 mg/kg) and tolbutamide (20 mg/kg) by i.v. infusion on two consecutive days. The plasma concentrations of the two drugs were determined during and after infusion. The average elimination half-life of hexobarbital had decreased from 325 to 122 min and of tolbutamide from 418 to 183 min following rifampicin treatment. It was calculated that the metabolic clearance of hexobarbital had increased about three-fold and that of tolbutamide more than two-fold. Significant changes in the distribution kinetics of the two drugs were not observed. The results suggest that rifampicin is capable of inducing drug metabolism in man, which leads to an increased rate of elimination of drugs that undergo biotransformation in the liver.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614021
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of dixyrazine and methaqualone on the sleep pattern in normal man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 227-231 
    Details
    ISSN: 1432-1041
    Keywords: Dixyrazine ; methaqualone ; etodroxizine ; Isonox® ; sleep stages ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Whole night EEG and polygraphic recordings were made in ten young, healthy, male volunteers after dixyrazine (12.5 mg, 25 mg, 50 mg), methaqualone (250 mg) and Isonox® (methaqualone 250 mg + etodroxizine 50 mg). A total of 156 recording nights (36 adaptation nights were not included in the analyses) were scored for different sleep stages according to accepted criteria. The smallest dose of dixyrazine (12.5 mg) had no significant effect upon sleep pattern: the larger doses (25 mg and 50 mg) caused significant decreases in REM-sleep during the first nights of administration. The decrease disappeared during the following two nights of treatment. No withdrawal effects were seen. Methaqualone also caused moderate depression of REM-sleep during the first night of treatment, and this effect, too, disappeared during prolonged administration. Isonox® (methaqualone + etodroxizine) had a somewhat stronger surpressive effect upon REM-sleep than methaqualone alone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567120
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  • 5
    Electronic Resource
    Electronic Resource
    Absorption of β-methyl-digoxin determined after a single dose and under steady state conditions (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 307-314 
    Details
    ISSN: 1432-1041
    Keywords: Absorption ; man ; β-methyl-digoxin ; serum concentration ; urinary excretion ; radio-immunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single doses of β-methyl-digoxin 0.4 mg were given to groups of 17 – 18 healthy volunteers as an intravenous infusion lasting 2 hours, or orally as Lanitop Liquidum® or Lanitop® tablets. The serum glycoside concentration and urinary glycoside excretion were measured over 8 and 32 h. The absolute bioavailability from the oral preparations in comparison with the infusion was lower for the first 8 h than for the entire 32 h of the investigation; the relative bioavailability from tablets was the same as from the solution for both periods. For both periods the area under the serum concentration/time curve and the urinary glycoside excretion were significantly lower after administration of the tablets than after intravenous infusion. Taking the average of both parameters, the absolute bioavailability of β-methyl-digoxin was about 80% from the solution and about 70% from the tablets. In 18 patients undergoing intravenous or oral therapy with β-methyl-digoxin steady state glycoside concentrations were compared in a cross-over study of intravenous maintenance therapy with Lanitop® ampoules or oral treatment with Lanitop® tablets. For a standard daily dose of 0.2 mg β-methyl-digoxin the serum concentrations were 1.35±0.10 ng/ml during both intravenous and oral administration. The intra-individual variation in glycoside concentration after changing from intravenous to oral maintenance therapy, or vice versa, was about the same as during continued intravenous or oral administration. It is concluded that the rate of rise of serum concentration after a single dose may be a useful indicator of the rate of absorption, but that the area under the serum concentration/time curve and the urinary glycoside excretion up to 32 h are unsuitable for determining equivalent doses of different formulations or routes of administration of digitalis glycosides.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561665
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  • 6
    Electronic Resource
    Electronic Resource
    Distribution and elimination kinetics of carbamazepine in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 91-96 
    Details
    ISSN: 1432-1041
    Keywords: Carbamazepine ; pharmacokinetics ; man ; diphenylhydantoin ; phenobarbital ; plasma binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Carbamazepine (2.7–3 mg/kg) was administered orally as an alcoholic solution (50% v/v) to eight healthy volunteers. Two of the subjects were also given 50 mg and 100 mg of carbamazepine in alcoholic solution and 200 mg as a tablet. Plasma concentrations, which were analysed by mass fragmentography, reached a maximum 1 – 7 hours after dosing, and then declined monoexponentially with half-lives ranging from 24 to 46 hours. The half-lives were independent of dose. The apparent distribution volume ranged from 0.79 to 1.40 l/kg. It was found that 72% of carbamazepine was bound to plasma proteins with little interindividual variation, and this was not influenced by the presence of diphenylhydantoin or phenobarbital in therapeutic concentrations. The pharmacokinetic parameters calculated from single oral doses were used to predict the steady-state plasma concentration expected after treatment with multiple doses of 200 mg three times daily. The predicted steady-state concentration was 2 – 3 times higher than that reported in patients undergoing chronic treatment with carbamazepine at this dose level, i.e. the pharmacokinetics of carbamazepine apparently change during multiple dosing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561556
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  • 7
    Electronic Resource
    Electronic Resource
    Disposition and oxidative metabolism of phenylbutazone in man (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 359-366 
    Details
    ISSN: 1432-1041
    Keywords: Phenylbutazone ; 14C-label ; oxyphenbutazone ; gas chromatography ; disposition ; oxidative metabolism ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption and elimination of orally administered14C-phenylbutazone and the role of oxidation in its metabolism have been studied. The main routes of excretion of14C-phenylbutazone and its metabolites were investigated in 3 patients with rheumatoid arthritis, and in 1 patient with a T-tube in the common bile duct. Up to 9 days after an oral dose of14C-phenylbutazone 600 mg (30 µCi) 63% of the radioactivity was found in the urine and 14% had appeared in the faeces. The cumulative excretion of radioactivity in bile amounted to 9.5% of the dose in 4 days. Only 1% of the radioactivity in the urine and bile was due to unchanged phenylbutazone. The role of oxidative metabolism of phenylbutazone in healthy human subjects was studied by gas chromatography. In 3 subjects given a single dose of phenylbutazone 600 mg, only 8.3% of the dose was excreted in urine as oxidized metabolites after 5 days. However, in 5 patients who had taken phenylbutazone for more than 5 weeks, these metabolites accounted for 23.4% of the dose. These results suggest that oxidative metabolism becomes more important after continued administration of the drug. After a single dose of phenylbutazone, the side-chain oxidized metabolite (II) was the major free derivative excreted in urine, but the ring oxidized metabolite, oxyphenbutazone (I), was much more important than the former in plasma. However, after prolonged treatment there was little difference between the concentration of the two metabolites in plasma. This finding suggests that side-chain oxidation is increased relative to ring oxidation on prolonged treatment with phenylbutazone. A third derivative containing hydroxyl groups both in the phenyl ring and in the side-chain (metabolite III) was found in urine in experiments with phenylbutazone, but in only one out of 3 volunteers given repeated doses of oxyphenbutazone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00566533
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  • 8
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of quinidine related to plasma protein binding in man (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 187-192 
    Details
    ISSN: 1432-1041
    Keywords: quinidine ; plasma protein binding ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition and plasma protein binding of quinidine after intravenous administration were studied in 13 healthy subjects. Plasma protein binding, expressed as the fraction of quinidine unbound ranged from 0.134–0.303 (mean 0.221). Elimination rate constant (β) varied from 0.071 to 0.146 h−1 (mean 0.113), and apparent volume of distribution (Vβ) varied from 1.39–3.20 l · kg−1β (mean 2.27). Total body clearance was 2.32–6.49 ml min−1 · kg−1. There was a positive linear correlation between the plasma fraction of unbound quinidine and both Vβ (r=0.885, p〈0.01) and total body clearance (r=0.668, p〈0.05). No significant correlation existed between the fraction of unbound quinidine in plasma and the elimination rate constant. The results show that both the apparent volume of distribution and total body clearance of quinidine are proportional to the unbound fraction in plasma. This implies that the total plasma concentration of quinidine at steady state will change with alterations in plasma binding, whilst the concentration of unbound compund and its elimination rate will remain unaffected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563104
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  • 9
    Electronic Resource
    Electronic Resource
    Smoking and catecholamine and c-AMP concentrations in the coronary circulation of man and the effect of oxprenolol (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 81-87 
    Details
    ISSN: 1432-1041
    Keywords: Oxprenolol ; smoking ; catecholamines ; coronary circulation ; man ; c-AMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Changes in catecholamine, c-AMP and lactate concentrations in the coronary circulation of man, during smoking, were studied in 12 patients. The heart rate increased from 63±2 beats/min (control) to 74±3 (smoking) (P〈0.01), falling to 70±2 (10 min after smoking) (0.05〉P〉0.01), whilst coronary sinus c-AMP concentrations rose from 11±0.7 nmol/l (smoking) to 11.9±0.8 nmol/l (after smoing) (0.05〉P〉0.01; one tailed ‘t’ test). There was no significant change in blood pressure, catecholamine or lactate concentrations. The study was repeated in eight of the patients following intravenous oxprenolol. Coronary sinus catecholamine concentrations increased from 4.1±0.7 nmol/l (control) to 5.5±1.1 nmol/l (after smoking) (0.05〉P〉0.01; one tailed ‘t’ test), but heart rate and c-AMP concentrations remained unchanged, confirming that smoking-induced tachycardia is a result of a β-adrenergic mechanism, at least part of which is due to a release of cardiac catecholamines. Arterial lactate concentrations increased only following oxprenolol from 0.74±0.07 mmol/l (control) to 0.83±0.09 mmol/l (smoking).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00645126
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