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  • pharmacokinetics  (2)
  • Acetylcholine release  (1)
  • 1
    ISSN: 1432-1041
    Schlagwort(e): prenalterol ; pharmacokinetics ; food ; congestive heart failure ; plasma levels ; urinary excretion ; metabolites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of prenalterol, a partial β-adrenoceptor agonist, has been studied in 12 patients with congestive heart failure, following single and repeated oral doses of 40 mg b.i.d. as controlled release tablets. A tracer dose of3H-labelled drug was given i.v. on 2 occasions to establish the variability of the pharmacokinetic parameters. Plasma levels and urinary excretion of prenalterol were measured after the oral and intravenous doses, and in addition, total radioactive metabolites were determined after the i.v. administration. Only small differences in the pharmacokinetics were observed when the i.v. tracer dose was given with the single oral dose or with the oral maintenance dose at steady state. The mean plasma elimination half-life was 2.4 h, the apparent volume of distribution 2.61/kg and the total body clearance about 800 ml/min. About 90% of the dose was excreted in urine, of which 30% was the parent drug. The remaining fraction comprised three metabolites, which were quantified by HPLC. Plasma levels of prenalterol close to steady state were obtained within 2 days and were maintained on a b.i.d. dosage regimen with controlled release tablets. The levels were independent of whether the tablets were taken fasting or with a standardized light meal. An average of 14% of the oral dose was recovered as prenalterol in urine after a single dose and 16% after a maintenance dose at steady state. Thus, about 45–55% of prenalterol reached the systemic circulation. The pharmacokinetic parameters in patients with congestive heart failure differed slightly from those in healthy subjects, but not sufficiently to require a change in the oral dosage regimen.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 6 (1973), S. 245-250 
    ISSN: 1432-1041
    Schlagwort(e): Procaine amide ; N-acetylprocaine amide ; sustained-release ; pharmacokinetics ; ventricular arrhythmia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Ten patients with acute myocardial infarction were studied during treatment with either a conventional or a new sustained-release preparation of procaine amide in order to compare fluctuations in plasma concentration and urinary excretion of the drug during “steady state” conditions. Procaine amide in plasma was measured by spectrofluorimetry and the urine concentration of it and its major metabolite, N-acetylprocaine amide, by gas chromatography. The average fluctuation of plasma concentrations was 3.5±0.1 µg/ml during treatment with sustained-release tablets (dosage interval 8 h) and 4.2±0.4 µg/ml during treatment with ordinary tablets (dosage interval 4 h), i. e. it was 20% greater during treatment with the conventional preparation. There was no difference between the two preparations in recovery of the drug from urine (sustained-release tablets 85.4±3.0%; and conventional tablets 90.3±5.4%). Thus, the new sustained-release preparation of procaine amide administered 3 times daily produced the same range of plasma levels as the identical dose of conventional tablets given 6 times a day.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 312 (1980), S. 1-6 
    ISSN: 1432-1912
    Schlagwort(e): Snake venoms ; Dendroaspis angusticeps ; Neurotoxins ; Neuromuscular facilitation ; Acetylcholine release
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The venom of the green mamba, Dendroaspis angusticeps has previously been shown to produce neuromuscular facilitation by increasing acetylcholine release. After gel filtration and ion-exchange chromatography of the whole venom, a basic polypeptide with facilitatory actions was isolated. This polypeptide, named dendrotoxin, has 59 amino acid residues, probably with only 3 disulphide bonds and a blocked N-terminus. When injected into conscious mice, dendrotoxin made the mice hypersensitive to external stimuli and subsequently produced respiratory paralysis. When tested on the isolated chick biventer cervicis nerve-muscle preparation, concentrations of dendrotoxin of 0.5 μg/ml (7×10−8 M) and greater, increased responses to indirect stimulation by 200–250%, without any increase in responses to submaximal concentrations of exogeneous acetylcholine, carbachol, KCl or direct stimulation. The augmentation was slow to develop, not reversed by washing, and could last several hours before slowly waning. Dendrotoxin did not produce spontaneous twitching or contractures. It is concluded that dendrotoxin is not an anticholinesterase, does not affect receptor sensitivity or muscle contractility, but produces twitch augmentation by increasing the amount of acetylcholine released by nerve stimulation. Thus, dendrotoxin appears to represent a snake venom neurotoxin with unusual chemical and pharmacological properties.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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