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  • man  (12)
  • Springer  (12)
  • National Academy of Sciences
  • 2010-2014
  • 1975-1979  (12)
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Keywords
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  • Springer  (12)
  • National Academy of Sciences
Years
Year
  • 1
    Electronic Resource
    Electronic Resource
    Plasma concentrations and urinary excretion of the antiarrhythmic quaternary ammonium compound QX-572 in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 277-282 
    Details
    ISSN: 1432-1041
    Keywords: QX-572 ; quaternary ammonium compound ; plasma level ; urinary excretion ; man ; anti-arrhythmic drug
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A quantitative thin layer chromatographic (TLC) method has been developed for determination of the antiarrhythmic quaternary ammonium compound N, N-bis (phenylcarbamoylmethyl) dimethylammonium chloride (QX-572) in biological materials. Prior to chromatography QX-572 was transferred into chloroform as perchlorate by ion pair extraction. Tritium-labelled QX-572 was used as the internal standard and a TLC scanning spectrophotometer equipped with a linear detector system afforded the required accuracy, specificity and simplicity. The method was used to determine QX-572 in plasma from 11 patients with various cardiac diseases who received QX-572 8 mg/kg body wt. as an intravenous infusion over 30 min. There was a rapid initial decay of the plasma levels from 11.0±1.1 µg/ml (mean ± SE) at the end of infusion to 3.5±0.5 µg/ml after 30 min. 240 min after commencement of the infusion the plasma level was 0.7±0.1 µg/ml. In these patients 22±2% (mean±SE) of the total administered dose of QX-572 was excreted unchanged in urine during the 24 hours following infusion of the drug. A second group of 28 patients with acute myocardial infarction also received QX-572 8 mg/kg body wt. Their plasma levels did not differ significantly from those found in the first group of patients. There was a poor correlation between the amount of QX-572 administered and plasma level at the end of the infusion. The study has provided some preliminary data about the pharmacokinetics of QX-572, but before a detailed analysis can be done data from longer periods of observation is required. The present results suggest that in future QX-572 can be administered in a standardized dosage, what would be advantageous in practice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567128
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  • 2
    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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  • 3
    Electronic Resource
    Electronic Resource
    Kinetics of nortriptyline in man according to a two compartment model (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 343-347 
    Details
    ISSN: 1432-1041
    Keywords: Nortriptyline ; pharmacokinetics ; man ; two compartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of nortriptyline have been assayed in four subjects after intravenous infusion of 57 mg nortriptyline hydrochloride. The data were evaluated according to a two compartment open model. The calculated best-fitting curves were in good agreement with the experimental data, better than could be expected from a simpler model. This justifies the assumption that the kinetics of nortriptyline in man may be described by this model with an appropriate input function. The data permitted estimation of all the parameters of the model. The meaning of the parameters is discussed, particularly in relation to individual variation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562660
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  • 4
    Electronic Resource
    Electronic Resource
    The metabolism of (−)-ephedrine in man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 193-198 
    Details
    ISSN: 1432-1041
    Keywords: (−)-[14C]-ephedrine ; metabolism ; urinary excretion ; tolerance ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The metabolic fate of orally administered (−)-[14C]-ephedrine has been studied in 3 human subjects and the urinary excretion of metabolites determined quantitatively by solvent extraction, paper chromatography and reverse isotope dilution procedures. Following an oral dose of the drug (0.35 mg/kg, 1.6 µCi), 97% of the dose was excreted in the urine within 48 h, 88% in the first 24 h. Unchanged drug was the major urinary excretory product (53–74%), with N-demethylation occurring to a variable extent (8–20%) although there was little interindividual variation in urine pH. Oxidative deamination was also variable (4–13%); the main identified products of this were benzoic acid (free and conjugated) and 1,2-dihydroxy-1-phenylpropane (free and conjugated). No phenolic metabolites could be detected, and thus it would appear that these compounds cannot be implicated in the acquisition of tolerance to ephedrine which can occur on repeated dosage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614017
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  • 5
    Electronic Resource
    Electronic Resource
    Some aspects of the intestinal absorption of zinc in man (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 423-428 
    Details
    ISSN: 1432-1041
    Keywords: Serum zinc concentration ; intestinal absorption ; portal vein ; transumbilical catheterization ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum zinc concentrations in peripheral venous blood were determined in 8 healthy volunteers at various times after oral administration of 50 mg Zn++. The same dose was given to 6 patients surgically treated for obesity by jejuno-ileostomy. In the healthy volunteers the mean serum zinc concentration before dosing was 0.89 µg/ml and a mean peak concentration of 2.39 µg/ml was found after 3 h. In the patients the starting level was lower, 0.67 µg/ml, and a mean peak concentration of 1.31 µg/ml was found 90 min after treatment. In the patients the areas under the serum concentration-time curve was approximately 1/3 of that in the healthy subjects. Zn++ 50 mg was also given to 3 patients undergoing transumbilical catheterization of the portal vein for diagnostic purposes and serum zinc concentrations were measured in portal and peripheral venous blood sampled simultaneously. No significant differences were found between the concentration of zinc in portal and peripheral venous blood during absorption, which suggests slow passage of zinc across the intestinal wall.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606559
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  • 6
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and bioavailability of indoprofen in man (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 257-262 
    Details
    ISSN: 1432-1041
    Keywords: Anti-inflammatory and analgesic drug ; indoprofen ; pharmacokinetics ; bioavailability ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a pharmacokinetic study of the new analgesic and anti-inflammatory drug indoprofen, plasma levels and urinary excretion were determined in four healthy volunteers after 100 mg and 200 mg iv, and after 100 mg (capsules) and 200 mg (tablets) oral doses. After iv administration, the mean biological half-life (t1/2 β) was about 2 h (range 1.4 to 3.2 h). The apparent volume of distribution Vdβ ranged between 11 to 17 % of body weight, indicating its limited extravascular distribution. Most of the drug was excreted in urine as glucuronide and a smaller proportion as unchanged indoprofen: the 24 h urinary excretion of these compounds accounted for 67 to 95 % of an iv dose. Peak plasma levels occurred between 30 and 120 minutes after oral administration of 100 mg as capsules or 200 mg as tablets. The mean biological half-life was about 2 h, as after iv administration. The bioavailability of oral doses was assessed using both plasma levels and urinary excretion data. The absorption of capsules and tablets was practically complete, that of the former being faster.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558338
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  • 7
    Electronic Resource
    Electronic Resource
    Inhibition of tetracycline absorption by zinc (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 59-62 
    Details
    ISSN: 1432-1041
    Keywords: Tetracycline absorption ; zinc sulphate ; zinc citrate ; complex formation ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The inhibitory effect of zinc on the gastrointestinal absorption of tetracycline has been investigated in 7 healthy volunteers. Zinc (45 mg Zn++) was given as a solution of zinc sulphate and as a zinc citrate complex; tetracycline (500 mg) was administered as a commercially available preparation. Serum tetracycline concentrations and the area under the serum tetracycline concentration-time curve (up to 6 h) were significantly reduced when tetracycline was taken with either zinc sulphate or the zinc citrate complex. Although the reduction of absorption seemed more pronounced after zinc sulphate, the difference between the inhibitory effects of the two forms of zinc was not significant. It is concluded that simultaneous administration of zinc and tetracycline may reduce absorption of tetracycline.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561551
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  • 8
    Electronic Resource
    Electronic Resource
    Effect of analgesic agents on emptying of the gallbladder in man (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 127-131 
    Details
    ISSN: 1432-1041
    Keywords: Gallbladder emptying ; analgesics ; indoprofen ; pentazocine ; morphine ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A controlled study of the clinical pharmacology of the biliary tract has been made. The rate of gallbladder emptying induced by a fatty meal was taken as a parameter for assessment of the inhibitory effect of indoprofen, a new analgesic-anti-inflammatory drug, pentazocine and morphine. The compounds were administered as single doses by iv (indoprofen and pentazocine) or im (morphine) injection. Indoprofen up to 400 mg had no effect, whereas morphine and pentazocine exerted a significant inhibitory effect on emptying of the gallbladder. Adverse reactions of clinical significance were associated with morphine and pentazocine, but were negligible with indoprofen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609471
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  • 9
    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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  • 10
    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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