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  • Artikel  (17)
  • man  (17)
  • Springer  (17)
  • Wiley
  • 2020-2020
  • 1970-1974  (17)
  • 1973  (11)
  • 1972  (6)
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  • Artikel  (17)
Verlag/Herausgeber
  • Springer  (17)
  • Wiley
Erscheinungszeitraum
  • 2020-2020
  • 1970-1974  (17)
Jahr
  • 1
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 5 (1972), S. 1-10 
    ISSN: 1432-1041
    Schlagwort(e): Tricyclic antidepressants ; desmethylimipramine ; nortriptyline ; single- and multiple-dose kinetics ; plasma concentration ; plasma clearance ; pharmacogenetics ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Eight healthy volunteers received single oral doses (1 mg/kg) and 6 received multiple doses (0.4 mg/kg t.i.d. for 2 weeks) of desmethylimipramine (DMI) and nortriptyline (NT) on different occasions. Kinetic analysis of plasma levels of the drugs showed that the ratios between single-dose peak-levels, plasma half-lives and apparent mean “steady-state” plasma levels of the two drugs were constant in all the subjects, and averaged 0.6. Despite their closely related chemical structures the apparent plasma clearance rate of DMI was about twice that of NT, and this might be associated with their different degrees of binding to plasma proteins. — The “steady-state” plasma level of NT in man is known to be genetically determined, and the conformity within each individual of the plasma clearance rates of DMI and NT indicates that the plasma kinetics of both these drugs are controlled by common genetic factors. — The study also shows that the “steady-state” plasma level of DMI, like that of NT, can be predicted accurately from single-dose plasma-level data. Thus, if the kinetic characteristics of one of these drugs in a subject are known, it is possible to predict the plasma kinetics of the other compound.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 5 (1972), S. 44-52 
    ISSN: 1432-1041
    Schlagwort(e): alprenolol ; serum drug level ; exercise ; man ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of alprenolol on heart rate and systolic blood pressure were studied in healthy subjects during standardized exercise on a bicycle ergometer. In one series of experiments, in which serum concentrations of alprenolol were also measured, the effects of single oral doses of 50, 100 and 200 mg of alprenolol and a placebo were compared by a double blind cross-over technique. In a second series of experiments 100 mg alprenolol was given four times in one day and the effect was followed for up to eighteen hours after the last dose. — Alprenolol diminished the expected increase in heart rate and systolic blood pressure during exercise. The reduction of exercise tachycardia in a given individual was linearly related to the logarithm of the dose or the serum concentration of alprenolol. The serum concentrations required for a given reduction of exercise tachycardia varied almost one hundred-fold amongst the subjects studied. The biological availability of alprenolol was dose-dependent, probably due to a limited capacity biotransformation of the drug before it entered the general circulation. After a single dose the serum level of alprenolol and its chronotropic effect diminished at a rate corresponding to an elimination half life of about two hours. This rate of elimination was consistent with that calculated from the results of the four dose study.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 5 (1973), S. 174-180 
    ISSN: 1432-1041
    Schlagwort(e): Tricyclic antidepressant ; nortriptyline ; metabolism ; urine ; pharmacokinetics ; twins ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The urinary excretion of nortriptyline (NT) and five of its metabolites was studied by quantitative gas chromatography in 22 twins and 7 unrelated healthy subjects after single (1 mg/kg) and multiple oral doses (0.4 mg/kg t.i.d.) of NT hydrochloride. A mean recovery of 62% of the dose was found after both single and multiple doses. The metabolite pattern in the urine was qualitatively and quantitatively identical in the two regimes, but there were marked variations in the pattern of metabolites between individuals. The disappearance rate of NT from the plasma was mainly determined by the metabolism of NT to 10-hydroxynortriptyline, which varied considerably between individuals. The data suggest that in certain rapid NT metabolizers, the upper limit for the overall clearance of NT from the plasma (if extrahepatic metabolism is assumed to be negligible) might be set by the blood flow through the liver.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 5 (1973), S. 181-185 
    ISSN: 1432-1041
    Schlagwort(e): Tricyclic antidepressant ; nortriptyline ; single-dose kinetics ; plasma/blood concentrations ; metabolites ; absorption ; availability ; apparent volume of distribution ; plasma/blood clearances ; gas chromatography-mass spectrometry ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The availability of an orally administered drug may be defined as the fraction of the total dose that enters the blood. Three healthy subjects were given identical doses of nortriptyline hydrochloride (NT-HCl) by the oral and intramuscular routes. The availability was assessed by comparing the total areas under the NT plasma concentration-time curves produced by the two methods of administration. The concentrations of NT in plasma and blood were determined by gas chromatography — mass spectrometry and were found to be almost identical. The observed availability of NT in these subjects ranged between 56 and 70% (mean 64%). The availability predicted from the parenteral plasma levels (assuming an average hepatic blood flow of 1.7 l/min) differed from the observed availability in one subject, perhaps because of the known variation in liver blood flow between individuals. The gastrointestinal absorption of NT-HCl was complete, since the recovery of the main metabolite, 10-hydroxynortriptyline, was the same after the two routes of administration. Pharmacokinetic analysis of the data showed that there might exist interindividual differences in the apparent volume of distribution of NT, (Vd)β. There was no apparent relationship between the variations in availability of NT and “steady-state” plasma levels or the disposition plasma half-lives of the drug. The calculated (Vd)β and (t 1/2)β of NT for each subject were in good agreement with those obtained from a previous study of single oral does of NT.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 6 (1973), S. 256-260 
    ISSN: 1432-1041
    Schlagwort(e): K 4277 ; anti-inflammatory agents ; metabolism ; man ; oral administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The fate of the new analgesic and anti-inflammatory agent α-[4-(1-oxo-2-iso-indolinyl)-phenyl]-propionic acid (compound K 4277) in healthy volunteers has been investigated by a radio-isotope method and gas-liquid chromatography. After oral administration, the drug was absorbed rapidly and completely and occurred in plasma mainly as unchanged compound bound extensively to plasma proteins. Its disappearance from plasma followed at least a bi-exponential function and was almost complete in 24 to 48 h. Most of the drug is excreted in urine as a glucuronide and a lesser amount as the unchanged compound. There were only negligible amounts of other metabolites.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 6 (1973), S. 57-60 
    ISSN: 1432-1041
    Schlagwort(e): Critical flicker fusion ; phenytoin ; phenobarbitone ; serum drug concentration ; man ; epilepsy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The central effects of single oral doses of phenobarbitone and phenytoin have been determined in six normal volunteers by measuring the critical flicker fusion threshold (CFF) under double-blind, placebo controlled conditions at intervals of up to 7 h after ingestion of the drug. Blood samples were taken at the same time for estimation of the serum concentration of the drugs by gas chromatography. Phenobarbitone in a dose of 180 mg produced a significant fall in CFF, and the time-course of this change mirrored the time-course of the serum concentration of the drug, which reached a peak of 21.8 µM (5.2 µg/ml) at 1.5 h. Phenytoin in doses of 200 mg, 300 mg and 400 mg produced no significant change in CFF even though an adequate serum concentration of the drug had been achieved (28.8 µM, 7.2 µg/ml, with the 400 mg dose). It was concluded that the two drugs differ in their action on the neural mechanisms tested by this procedure.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 6 (1973), S. 177-180 
    ISSN: 1432-1041
    Schlagwort(e): Amphetamine ; drug dependence ; metabolism ; urine ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The metabolism of (+)-[14C] amphetamine has been studied in two women who had been taking 90–100 mg of Dexedrine ((+)amphetamine sulphate; Smith, Kline & French) daily for several years but who showed no evidence of overt amphetamine toxicity. The urinary metabolites were identified, estimated and compared with the results previously obtained from two drug naive male subjects who had received 20 mg of (±)amphetamine (Caldwellet al., (1972b). The same metabolites were found, but the dependent subjects excreted in 24 h more unchanged amphetamine (about 30% of dose) than the naive subjects (20%). This may be a reflection of the dose, which in dependent subjects was five times that of naive subjects. The dependent subjects excreted in 24 h slightly more norephedrine (2.9, 4.1% of dose) and 4′-hydroxynorephedrine (1.1, 1.6%) than the naive subjects (norephedrine, 2.2, 2.6%; 4′-hydroxynorephedrine, 0.3, 0.4%), but the difference in percentage of dose may not be significant. However, in absolute terms the dependent subjects are producing at least five times as much norephedrines as the naive subjects because of the larger dose.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 6 (1973), S. 187-190 
    ISSN: 1432-1041
    Schlagwort(e): Methaqualone ; single dose kinetics ; plasma concentration ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma concentrations of methaqualone were followed for several days after single oral doses in 5 healthy subjects. The analysis of methaqualone was performed by gas chromatography-mass spectrometry (mass fragmentography). The plasma levels of methaqualone were interpreted according to a two compartment model. The elimination rate of methaqualone was found to be much slower than has been reported previously, half lives in the β-phase ranging from 19.6 to 41.5 h.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 6 (1973), S. 228-233 
    ISSN: 1432-1041
    Schlagwort(e): Dopamine-β-hydroxylase ; man ; plasma ; sympathetic activity ; halothane
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary As an index of sympathetic nervous system activity, the level of dopamine-β-hydroxylase (DBH) in plasma was measured in 82 children, mean age 6±0.3 years, before and during halothane anaesthesia. Plasma DBH fell markedly in 50% of cases irrespective of the anaesthetic technique, i.e. halothane with or without nitrous oxide, and with or without premedication by pethidine and/or atropine; enzyme activity was unchanged in 25% of the children; and in the remaining 25%, DBH activity increased. The heart rate fell significantly in cases in whom DBH activity was lowered, and it remained almost unchanged, when DBH rose during anaesthesia. A fall in plasma DBH activity during anaesthesia was found particularly in children who appeared excited and anxious before anaesthesia; enhanced preanaesthetic sympathetic tone in this group was indicated by plasma DBH activities and heart rates higher than in the other groups. It is concluded that halothane may not only reduce elevated sympathetic activity, but also in most cases may oppose sympathetic counter-regulation which should occur in reponse to its direct cardiovascular depressant effect.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 5 (1973), S. 236-238 
    ISSN: 1432-1041
    Schlagwort(e): Activated charcoal ; tricyclic antidepressant ; nortriptyline ; intoxication ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Six healthy volunteers were given nortriptyline (NT) in doses of 0.86–1.00 mg/kg. There was a significant (P〈0.05) decrease in absorption of the drug if 5 g of activated charcoal was administered half an hour afterwards.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 11
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 4 (1972), S. 201-205 
    ISSN: 1432-1041
    Schlagwort(e): Tricyclic antidepressant ; nortriptyline ; metabolism ; stereospecific hydroxylation ; plasma kinetics ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Thecis andtrans isomers of 10-hydroxynortriptyline (10-OH-NT), the major metabolite of nortriptyline (NT) in man, have been separated and quantitated in urine from 6 healthy volunteers who received NT orally, 0.4 mg/kg body weight, three times daily. The isomers were separated by preparative thin layer chromatography and quantitatively determined by gas chromatography as the 10,11-dehydronortriptyline heptafluorobutyryl derivative. The structure of these derivatives producedin vitro was confirmed by gas chromatography — mass spectrometry. Less than 1% of totally excreted 10-OH-NT was accounted for as 10,11-dehydronortriptyline. — Despite interindividual differences in the mean steady-state plasma concentration of NT, the ratio between the two isomers was constant in all subjects (1:4–5). The isomers were both optically active and circular dichroism spectra showed that the asymmetric carbon atoms in the two compounds have different configurations. — It is concluded that NT undergoes stereospecific hydroxylation in man and that there is no correlation between the mean steady-state plasma concentration of NT and the proportion of thecis andtrans isomers formed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 5 (1972), S. 62-64 
    ISSN: 1432-1041
    Schlagwort(e): GLC ; fenfluramine ; norfenfluramine ; blood levels ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A new analytical procedure is described for the determination of fenfluramine and norfenfluramine in biological specimens. Fenfluramine and norfenfluramine are converted to the trichloroacetyl derivatives, separated on a 3% OV 17 — Chromosorb Q glass column and measured by ECD. The rapidity, sensitivity and specificity of the technique fulfil all the requirements for routine clinical use.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 13
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 6 (1973), S. 181-186 
    ISSN: 1432-1041
    Schlagwort(e): Phenothiazines ; thioridazine ; serum levels ; pharmacokinetics ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The rate of absorption of thioridazine varied greatly in ten healthy volunteers who took 100 mg in the morning after an overnight fast. The peak level in blood was also variable and it was reached 1 1/4 to 4 h after dosing. Maximal concentrations in the blood varied widely from 0.13 µg/ml to 0.52 µg/ml. No relation was found between the weight or sex of the subjects and the pharmacokinetics of the drug. The serum half life of thioridazine in three healthy volunteers was 9, 10 and 10 h respectively. In a group of 22 patients receiving less than 5 mg/kg body weight a day, there was a strong correlation between the dose and the morning or evening concentration of thioridazine in the blood. A positive correlation was also observed between the age of the patient and the serum level in those who received doses of less than 5 mg/kg body weight.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 14
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 6 (1973), S. 261-267 
    ISSN: 1432-1041
    Schlagwort(e): Alclofenac ; antiphlogistic ; man ; pharmacokinetics ; dosage regimes ; plasma levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A one compartment open model has been found to fit plasma concentration data previously obtained in man after single oral doses of alclofenac; the parameters of the model are: $${\text{t}}_{\tfrac{{\text{1}}}{{\text{2}}}} $$ abs=1.3±0.7h, $${\text{t}}_{\tfrac{{\text{1}}}{{\text{2}}}} $$ el=3.5±1.2h, Vd/F=17±6. The model has been used successfully to predict steady-state plasma levels of alclofenac after multiple oral doses. One treatment schedule (initial dose 500 mg, maintenance dose 250 mg five times a day) was administered to two volunteers for five days and the plasma levels of alclofenac determined daily. The latter were in good agreement with computer predictions based on the model. It is now possible, therefore, to select the most suitable dosage regimes for this drug.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 15
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 5 (1973), S. 214-217 
    ISSN: 1432-1041
    Schlagwort(e): Pindolol ; beta-blockade ; oral administration ; man ; alprenolol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The duration of beta-receptor blockade after single oral doses of LB-46 has been investigated by the isoproterenol infusion technique. A single 5 mg dose of LB-46 caused beta-receptor blockade lasting for 45 min to about 15 h; the range of action after 10 mg LB-46 orally was 30 min to 24 h. The duration of action of an equipotent dose of alprenolol was shorter. The therapeutic implications of these results are discussed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 16
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 4 (1972), S. 65-73 
    ISSN: 1432-1041
    Schlagwort(e): Drug metabolism ; cytochrome P-450 ; needle biopsy ; liver injury ; man ; enzyme assay
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A micromethod is described for determination of the cytochrome P-450 content, demethylation rate of aminopyrine and p-nitroanisole, the activities of NADPH-cytochrome-c-reductase, pseudocholinesterase and glucose-6-phosphatase in homogenates of the small amount of human liver (about 20 mg) obtained by needle biopsy. 1 g of human liver contains 32–38 mg microsomal protein, much less than that present in rat liver (50–60 mg/g liver). The cytochrome P-450 content in normals was 10.8±2.6 nmoles/g liver wet weight (mean±1 S.D.). In severe hepatitis and cirrhosis the cytochrome P-450 content fell to 50% of the control value, whereas mild and moderate hepatitis did not produce any change. Similarly, only in seriously damaged livers were the demethylationrates of both substrates lowered. The activity of the NADPH-cytochrome-c-reductase was 1.88±0.51 micromoles/g liver × min and was not impaired even by severe liver damage. The activities of glucose-6-phosphatase and pseudocholinesterase also fell only in severe liver disease.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 17
    ISSN: 1432-1041
    Schlagwort(e): Tricyclic antidepressant ; nortriptyline ; single- and multiple-dose kinetics ; plasma concentration ; plasma clearance ; predictability ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Six healthy volunteers were given nortriptyline (NT) in single (1 mg/kg) and multiple (0.4 mg/kg) oral doses with the purpose to study the pharmacokinetics of NT in plasma. The single-dose plasma levels in 3 subjects were applied to a two-compartment open model (Model II) which might be suitable for the disposition kinetics of NT. There were significant (P〈0.0005) interindividual differences in the observed mean steady-state plasma concentration,C-0304;, of NT which ranged from 51.7 to 111.0 ng/ml.C-0304; was better correlated to the single-dose plasma clearance rate of NT (r=0.98;P〈0.0005) than to the single-dose plasma half-life, (t 1/2)β, (r=0.89;P〈0.05). Thus the steady-state plasma level can be accurately predicted from single-dose studies. The apparent volume of distribution of NT at pseudodistribution equilibrium, (V d)β, varied between 21.1 and 31.1 lit./kg body weight assuming complete absorption of the administered dose. There was no significant correlation (r=0.56) between the single-dose and post steady-state plasma half-lives of NT within individuals. NT does not seem to affect its own metabolismin vivo in man since the single- and multiple-dose plasma clearance rates of the drug were similar within subjects. It is concluded that there might be interindividual differences in both the apparent elimination rate and in the distribution of NT. This may be of importance in the pharmacogenetics of NT.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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