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  • Artikel  (641)
  • pharmacokinetics  (590)
  • man  (71)
  • Springer  (641)
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  • 1
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of di-n-propylacetate in epileptic patients (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 97-105 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Di-n-propylacetate ; 2-propyl-valeric acid sodium salt ; pharmacokinetics ; anti-epileptic ; drug monitoring ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of the anti-epileptic drug di-n-propylacetate (DepakineR) have been studied in 7 patients, in whom plasma concentrations were determined during and following subchronic treatment. Elimination of the drug appeared to follow a monophasic exponential course; biological half lives were 8 to 15 hours. The data supported the assumption that an open one-compartment model can be used to describe the kinetics of dipropylacetate in man. The drug appeared to have a relatively restricted distribution: calculated relative distribution volumes ranged from 0.15 to 0.40 1/kg. There were large interindividual differences in clearance rate. The therapeutic range was considered to be between 50 and 100 mg/1 plasma. Plasma levels of phenobarbital were markedly raised during treatment with dipropylacetate for an unknown reason. Determination of the plasma concentrations of drugs at accurately fixed times appears to be a reliable method for pharmacotherapeutic monitoring of epileptic patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561557
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Concentrations of the vasodilator isosorbide dinitrate and its metabolites in the blood of human subjects (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 157-160 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Isosorbide dinitrate ; pharmacokinetics ; metabolism ; pharmacological action ; nitrates
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary An oral dose of 5 mg of14C-isosorbide dinitrate was rapidly absorbed, biotransformed and excreted by human subjects. Peak whole blood concentrations of radioactivity were reached after 1.5 to 2 hours and declined relatively slowly. The radioactivity in whole blood mainly represented metabolites, isosorbide mononitrates. The peak concentrations found were 4.5, 11.7 and 34.3 ng/ml of isosorbide dinitrate, isosorbide 2-mononitrate and isosorbide 5-mononitrate, respectively, in the blood of one subject and 5.9, 15 and 61.3 ng/ml, respectively, in the blood of another subject. However, concentrations of the metabolites declined relatively slowly during 6 h after the oral dose. Up to 99% of an oral dose of isosorbide dinitrate was excreted during 5 days, mainly in the urine of the first day (ca. 78%). The results showed that isosorbide mononitrates were available to contribute to the pharmacological action.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00567108
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  • 3
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Sympathetic activity ; plasma catecholamine concentration ; dopamine-β-hydroxylase activity ; graded physical exercise ; heart rate ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00567112
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Bioavailability of m-octopamine in man related to its metabolism (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 33-39 
    Details
    ISSN: 1432-1041
    Schlagwort(e): m-octopamine ; metabolism ; first-pass effect ; man ; enteric absorption ; monohydroxylated phenylalkylamines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The diminished sympathomimetic pressor activity of monohydroxylated phenylalkylamines after oral administration has been attributed to incomplete enteric absorption. Therefore, urinary excretion of the unchanged drug and its metabolites has been compared after intravenous and oral administration of3H-m-octopamine to eight patients. Identical amounts of3H-activity (80% of the dose) were excreted after the two routes of dosing, so enteric absorption has been assumed to be complete. Significant differences were found in the fraction of free urinarym-octopamine, which amounted to 10.5% of the dose after infusion and 0.58% after oral administration. The only metabolic pathways form-octopamine are deamination and conjugation. Following oral administration the percentage of conjugates was considerably higher than after intravenous infusion. This metabolic pattern appears typical of all phenylalkylamines with a hydroxyl group in themeta position. Ring hydroxylation to catecholamines was not observed. The enzymes mainly responsible for conjugation after oral administration are located in the gut wall. The resulting “first pass effect”, i.e. metabolism prior to the access to the central compartment, can account for the diminished pharmacodynamic effect after dosing by this route.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00616412
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  • 5
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Oxyfedrine ; norephedrine ; man ; urinary excretion ; sympathomimetic
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00567109
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  • 6
    Digitale Medien
    Digitale Medien
    Pharmacokinetics — Uses and abuses (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 241-248 
    Details
    ISSN: 1432-1041
    Schlagwort(e): pharmacokinetics ; experimental design
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary It is apparent from studying recent articles on pharmacokinetics that a number of misunder-standings exist, both about the design of experiments and the analysis of results. The purpose of this paper is to outline many of the common pitfalls associated with the design of experiments and also the limitations upon the analysis of results. The paper describes mathematical, laboratory and clinical aspects which must be examined in designing a protocol for pharmacokinetic experiments. Simulated data is presented to demonstrate the dangers of using standard computer programs for parameter estimation. Even when convergence is obtained the answers may be dependent on the method employed. A mathematical model is of little use unless a reasonable amount of good, accurate data is obtained.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00567122
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and side-effects of clonazepam and its 7- amino-metabolite in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 249-254 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Clonazepam ; 7-amino-clonazepam ; pharmacokinetics ; side-effects ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Clonazepam (CNP) and its principal metabolite in plasma, 7-amino-CNP (ACNP), have been investigated in a prospective study of 27 newly diagnosed epileptics and correlated with specified side-effects. At a daily dose of 6 mg, the average plasma levels of both substances were about 50ng/ml, and individual values ranged from 30 to about 80ng/ml. There was a linear correlation between changes in dose and the resulting plasma levels, which indicates first order elimination kinetics. Side-effects were frequent, but neither their severity nor their occurrence could be related to plasma levels or to the rate of increase in plasma concentration of the drug. Three out of five patients who developed serious dysphoria had significantly high CNP levels. The concentration of ACNP was considerably increased in four patients who subsequently suffered from withdrawal symptoms. Drug interaction with diphenylhydantoin, i.e. decreased CNP level, was observed in all five patients who received both compounds. In general it is not yet possible to define an upper limit for the plasma levels of CNP and ACNP at which toxicity occurs. In patients treated with conventional doses of CNP, measurement of plasma concentration is not required, except in special circumstances, because of the lack of correlation between plasma level and side-effects.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00567123
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  • 8
    Digitale Medien
    Digitale Medien
    Anticoagulant effect and plasma kinetics of fluorophenindione after a single dose in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 271-275 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Fluorophenindione ; vitamin K antagonist ; pharmacokinetics ; loading dose ; anticoagulant
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary After administration of a single loading dose (80 mg p.o.) of fluorophenindione, the prothrombin level decreased to 37 % in 24 h, and the effect lasted for 48 h. Accordingly, fluorophenindione can be classified as an anticoagulant with an “intermediate” effect. Its elimination half-life was 31 h, which is longer than that of phenindione, because of the greater stability of the fluorinated derivate.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00567127
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  • 9
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Nortriptyline ; pharmacokinetics ; man ; two compartment model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562660
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  • 10
    Digitale Medien
    Digitale Medien
    Delayed absorption of lithium in intoxication (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 285-285 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Lithium ; intoxication ; man ; delayed absorption ; gastric contents
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A 55-year old man with lithium intoxication showed increasing serum concentrations in spite of forced diuresis and dialysis. A high lithium content was found in gastric juice three days after the compound had been taken. The serum lithium level began to fall after gastric lavage.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00567130
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