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  • 1
    ISSN: 1432-1041
    Keywords: Chlorthalidone ; diuretics ; drug plasma concentration ; protein binding ; red blood-cell concentration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A gas chromatographic method has been employed to determine chlorthalidone in plasma and whole blood after therapeutic doses. Radioactively labelled chlorthalidone was used for in vitro studies of the uptake of chlorthalidone from plasma by red blood cells. Chlorthalidone was markedly concentrated in red cells and as a compartment they would account for at least 30% of total drug in the body after multiple doses. The ratio between the plasma and red cell concentration of chlorthalidone varied between individuals. After a single oral dose of 50 mg in 6 healthy volunteers chlorthalidone was eliminated with a half-life of 51 to 89 hours. The apparent volume of distribution varied between 3 and 13 1/kg and the clearance between 53 and 145 ml/min. The mean steady-state plasma concentrations during treatment with a standard dose of 50 mg daily (n=10) varied 5-fold between individuals. During the steady state approximately 50% of the daily dose was excreted unchanged in the urine during 24 hrs. The plasma levels observed in patients were higher than those predicted from the single oral dose studies in healthy volunteers.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 8 (1975), S. 359-363 
    ISSN: 1432-1041
    Keywords: Diphenylhydantoin metabolites ; human urine ; gas chromatography ; 4-hydroxydiphenylhydantoin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A modified gas chromatographic procedure for the determination of unconjugated and conjugated 4-hydroxydiphenylhydantoin (4-OH-DPH) in urine has been developed. Unconjugated 4-OH-DPH is determined after selective extraction with toluene — ether (1:1). For the assay of conjugated 4-OH-DPH, the urine is pre-extracted withisoamylalcohol before acid hydrolysis to avoid interference by the dihydrodiol metabolite of DPH. The sensitivity of the method is 0.1 µg per ml. The method has been used to determine the urinary metabolites in two adult volunteers, during steady state plasma concentrations of DPH and in the elimination phase.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: Drug hydroxylation ; drug interaction ; drug plasma levels ; nortriptyline ; 10-hydroxynor-triptyline ; perphenazine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels of nortriptyline and perphenazine were measured in six patients on continuous nortriptyline treatment before, during and after oral administration of perphenazine 4 mg t.i.d. In four patients the plasma levels of the conjugated and unconjugated principal metabolite 10-hydroxy-nortriptyline were also measured. Urinary excretion of conjugated and unconjugated 10-hydroxy-nortriptyline and plasma levels of perphenazine were determined in all six patients. During treatment with perphenazine two patients showed a slight increase in the plasma level of nortriptyline. The changes in metabolite excretion rate were inconclusive. Thus, there did not appear to be any important pharmacokinetic interaction between the two drugs at the doses used, which were normal therapeutic doses. The previously reported inhibitory effect of perphenazine on the metabolism of nortriptyline probably depended therefore, either on administration of a higher dose of perphenazine, or on treatment in the reverse sequence — a single dose of nortriptyline was given to patients already receiving perphenazine.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 31 (1986), S. 415-418 
    ISSN: 1432-1041
    Keywords: pindolol ; age effect ; pharmacokineticsrenal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and beta-blocking effect of pindolol has been compared in 20 patients with essential hypertension (WHO Stage I), 10 below 25 years of age and 10 older than 60 years. Each patient received pindolol 10 mg p.o. once a day for 5 days. The area under the curve (AUC) of pindolol was larger in the old than in the young patients both on the first (p〈0.05) and the fifth (p〈0.01) days. The AUC of pindolol was 14% higher on the fifth day compared to the first day in the elderly group, indicating minor accumulation at steady-state. There was no change in AUC in the young patients. Endogenous creatinine clearance was lower in the old (80±9 ml/min) than in the young patients (150±45 ml/min). The beta-blocking effect did not differ between the groups at 2h after administration of pindolol on Days 1 or 5. However, 24 h after the first and fifth doses approximately 60% of the beta-blockade persisted in the old group whereas 17 and 19% of the beta-blockade, respectively, persisted in the young group; the difference between the groups was statistically significant (p〈0.01). The most probable explanation for the more sustained beta-blocking effect in the elderly is the physiologically decrease in renal function, which results in a more sustained plasma level of pindolol in those patients.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 29 (1986), S. 529-534 
    ISSN: 1432-1041
    Keywords: pethidine ; epidural injections ; pain scores ; kinetics ; spinal cord
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-one patients who had undergone total hip replacement were randomly assigned to one of three groups in order to compare a single dose of 1 mg/kg of pethidine im (I) and 20 mg (II) or 60 mg of extradural pethidine (III) in a double-blind design. The degree of analgesia, the adverse effects, and the kinetics were studied for 18 h. Pain was monitored using a visual analogue scale (VAS). Supplementary doses of oxycodone if required were given no earlier than 0.75 h after pethidine. Plasma concentrations of pethidine were measured with gas chromatography mass spectrometry (GCMS). Hypoalgesia to pin prick test was evaluated. Low pain scores were observed in the extradural groups between 0.25 and 1.5 h after the dose. A significant difference in pain score compared with the im group was found after the higher extradural dose only between 0.5 and 1 h (p〈0.05). The area under the curve (AUC) of pain score versus time (0–18 h) was not significantly different between groups. The recorded adverse effects were minor in all three groups. The terminal half-lives and plasma clearances of pethidine, and the time to peak concentration were not different between the groups. Single patients in the extradural groups showed hypoalgesia to pin prick in parallel to the effect. The present study shows that extradural pethidine produces shortlived analgesia, in contrast to the long-lasting effect of morphine found in other studies.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0003-2697
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography A 140 (1977), S. 165-169 
    ISSN: 0021-9673
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography A 68 (1972), S. 77-88 
    ISSN: 0021-9673
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography A 116 (1976), S. 53-61 
    ISSN: 0021-9673
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 56 (2000), S. 103-120 
    ISSN: 1432-1041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Will it take a series of drug-related accidents that have already occurred in the USA before workplace drug testing (WDT) becomes accepted in Europe as a preventive measure? Currently, the development of WDT in most European countries lags some 10–15 years behind that in the USA. – Labour authorities in Europe now ought to take initiatives to demand a mandatory programme for accrediting drug analytical laboratories for WDT. – Companies should realise that illicit drug use is no longer only a problem at street corners, and that having a testing system in place is important, not just for public health, but also for their reputations as responsible societal actors. – Improved networking among police and regulatory authorities is required to keep pace with the rapid appearance and dissemination of new substances of abuse. – European research collaboration, including the newly formed European Workplace Drug Testing Group, is needed to assess the impact of drug-testing policies on accidents and other outcome variables, and thereby to convince the general public and politicians that drug testing is beneficial and necessary. – A 1993–1994 survey of quality analysis in some 200 European laboratories reported from Institut Municipal d'Investigació Mèdica (IMIM), Spain, showed good agreement between nominal and found concentrations but that only 10% of the laboratories could both screen, identify and quantify samples. – Experiences from Italy show that proficiency testing schemes lead to improved accuracy of results. These were some major conclusions of the First European Symposium on Drug Testing held at Huddinge University Hospital in Stockholm, Sweden, 30 March to 1 April 1998, organised by Karolinska Institute, with participants from 22 countries.
    Type of Medium: Electronic Resource
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