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  • 1980-1984  (4)
  • 1
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The haemodynamic effects and pharmacokinetics of a single orally administered dose of 0.5 mg of prazosin have been compared in six patients with stable severe congestive cardiac failure. Administration of prazosin induced significant decreases in mean pulmonary capillary wedge pressure (from 27.5, s.e.m.=4.5 to 19.4, s.e.m.=5.1 mmHg; P〈0.001), mean arterial blood pressure (from 94.5, s.e.m.=6.0 to 85.4, s.e.m.=5.0 mmHg; P〈0.01), and systemic vascular resistance (from 1690, s.e.m.=360 to 1420, s.e.m.=200 dyn. s/cm5; P〈0.05) and a rise in cardiac index from 1.98 (s.e.m.=0.07) to 2.28 (s.e.m.=0.16) litres/min per m2 (P〈0.05). There was a non-significant fall in heart rate.2. Pharmacokinetic analysis revealed maximum plasma prazosin concentrations of 4.1 (s.e.m.=1.4) ng/ml, occurring 2.1 (s.e.m.=0.4) h after drug ingestion. The mean elimination half-life was 5.1 (s.e.m.=0.8) h, which is longer than that found in our previous studies in normal subjects. There was considerable interindividual variation in peak plasma prazosin concentrations, elimination half-life and area under the concentration-time curve. While mean maximal haemodynamic effects of prazosin occurred at similar times to the peak plasma concentration of the drug, there was no significant correlation between the extent of haemodynamic response and individual pharmacokinetic parameters.3. It is concluded that significant and potentially beneficial haemodynamic effects occur with the initial administration of 0.5 mg oral doses of prazosin in patients with stable congestive cardiac failure and it is suggested that in many patients little advantage will be achieved with higher initial doses.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 8 (1981), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Individual anterior hypothalamic-preoptic nuclei were dissected from the brains of control and α-methyldopa treated (2 × 40 mg/kg, 5 days) rats, and the concentrations of adrenaline and other catecholamines were estimated.2. By a combination of radioenzymatic assay and paper chromatography the concentrations of adrenaline, noradrenaline, dopamine, α-methylnoradrenaline and α-methyldopamine were determined concurrently in the same sample.3. α-Methyldopa reduced the adrenaline levels of the hypothalamic nuclei by 47–68% of control concentrations.4. A differential displacement of the parent catecholamines was observed and the depletions were ranked: adrenaline 〈 dopamine 〈 noradrenaline.5. α-Methylnoradrenaline and α-methyldopamine were found in all hypothalamic nuclei.6. The depletion of hypothalamic adrenaline by α-methyldopa could represent a pharmacological mechanism contributing to the antihypertensive action of the drug.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 6 (1981), S. 59-64 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The renal excretion and clearance of methotrexate (MTX) following high-dose (800 mg) therapy followed by folinic acid rescue was studied in 12 patients (2 female, 10 male): the mean age was 49.3±5.5 (SE), weight 68.6±3.9 (SE) and body surface area 1.8±0.1 m2. Plasma and urine were collected over 154 h at intervals of 2–24 h, and the collection times, volume, and pH of urine samples recorded. Total MTX concentrations in urine and plasma were measured by the highly specific competitive protein-binding assay method. Plasma and urinary creatinine levels were measured on an SMA-12 autoanalyser. The renal clearance of MTX was calculated for each urine collection period. Following oral administration, clearance values during the first 6 h were high at 257±8.3 (ml/min), followed by a trough in clearance of 27.9±4.2 (ml/min) in the 20- to 30-h period. This was followed by a secondary rise of MTX renal clearance to 180.4±14.6 ml/min during the 68- to 84-h period and again to 84.9±17.1 ml/min between 84 and 112 h. In the last two periods it rose to 209±57.9 ml/min. Similar fluctuations were seen following IV administration. The changes in clearance were statistically significant at the P〈0.005 level. It is suggested that high concentrations of MTX in the renal tubules result in inhibition of carrier protein synthesis, leading to a fall in active tubular secretion. When MTX concentrations fall the tubular cell recovers and a secondary rise in renal clearance occurs, leading to cyclical changes in MTX elimination.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 23 (1982), S. 1-5 
    ISSN: 1432-1041
    Keywords: clonidine ; noradrenaline ; pharmacokinetics ; arterial blood pressure ; plasma concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of clonidine and its relation to blood pressure response and side effects were studied after single oral doses of 75 µg, 150 µg and 250 µg in normotensive subjects. Following oral administration, the drug was absorbed rapidly after an initial lag time of 19–22 min and peak levels were reached between 2.4 and 2.9 h. Sampling over 48 h was necessary for accurate estimation of pharmacokinetic parameters. Post-peak plasma concentration declined in a monoexponential manner and the half-life of the elimination phase ranged from 9.0 to 15.1 h. Maximum plasma concentration (Cmax) and area under curve (AUC) increased proportionally with increasing doses. Clonidine produced significant reductions in the pulse rate and a dose dependent decrease in blood pressure. Clonidine (150 µg) also produced significant reductions in plasma catecholamine levels.
    Type of Medium: Electronic Resource
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