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  • pharmacokinetics  (2)
  • AC-ECD  (1)
  • Springer  (3)
  • Munksgaard International Publishers
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  • Springer  (3)
  • Munksgaard International Publishers
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Microchimica acta 96 (1988), S. 11-26 
    ISSN: 1436-5073
    Keywords: electron capture detector (ECD) ; electron oscillation ; AC-ECD ; argon-methane ; non-homogeneous ECD kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The oscillation of electrons—as driven by AC polarization—can be used to extract a high-sensitivity signal from a conventional electron capture detector. For example, hexachloroethane was detected at a hypercoulometric ratio of 2.0 F/mol, down to ca. 60 fg/s (S/N=3) and with a linear range in excess of two orders of magnitude. The change in carrier gas from nitrogen to argon-methane produced the expected order-of-magnitude increase in optimum oscillation frequency. Anab initio simulation of potentials and ion populations in a heterogeneous electron capture system under a high-frequency AC regime provided further insight into the detector's mechanism: Hypercoulometric response is mainly caused by increased cation-electron recombination in the plasma region, owing to a decreased field gradient and an increased cation concentration.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: Captopril ; sublingual ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In this study we compared the pharmacokinetics and pharmacodynamics of captopril after sublingual and peroral administration. Single 25 mg doses of captopril were administered sublingually and perorally on two different occasions in a randomised cross-over fashion to eight healthy volunteers aged 22–35 years. The kinetics of unchanged captopril, plasma renin activity (PRA), BP and heart rate were studied over three hours after both peroral and sublingual administration of captopril. Mean pharmacokinetic parameters for unchanged captopril after sublingual administration were: Cmax, 234 ng·ml−1; tmax, 45 min; AUC (0–3 h), 15.1 μg·ml−1. min. Mean pharmacokinetic parameters for unchanged captopril after peroral administration were: Cmax, 228 ng·ml−1; tmax, 75 min; AUC (0–3 h), 17.0 μg·ml−1. min. tmax was significantly shorter when captopril was administered sublingually; all other pharmacokinetic parameters were equivalent. The plasma captopril concentrations achieved post drug administration led to increases in PRA and reductions in BP. tmax for PRA was 86 min for sublingual captopril and 113 min for perorally administered drug. Peak PRA values were, however, not significantly different. BP, as expected, was not reduced dramatically in these healthy volunteer subjects, however, in systolic BP vs time profiles, BP was significantly lower after volunteers received sublingual captopril. Heart rate increased slightly after captopril administration; there were no differences between the two routes of administration. Administration of captopril sublingually, therefore led to a more rapid attainment of plasma captopril concentrations and had a more rapid onset of pharmacological effect when compared with peroral administration.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: alfuzosin ; prazosin ; alpha1-adrenoceptor antagonist ; noradrenaline ; pharmacokinetics ; pharmacodynamics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open dose ranging study with random inclusion of placebo, alfuzosin (α1-adrenoceptor antagonist) 1, 2.5 and 5 mg was administered to 6 healthy volunteers, 3 of the volunteers received 10 mg alfuzosin. Supine systolic blood (SBP) pressure was not reduced by alfuzosin although significant increases occurred in supine heart rate (HR) after 2.5 and 5 mg. In the standing position, SBP was reduced at 2 and 4 h with 5 mg alfuzosin; significant increases in HR occurred following 1, 2.5 and 5 mg at 2, 4, 6 and 8 h after administration. Exercise SBP was not reduced; diastolic blood pressure was significantly reduced at 4 and 6 h with 5 mg alfuzosin. More marked effects were seen in the 3 subjects who received 10 mg alfuzosin. After 1 and 5 mg, tmax ranged from 1–2 h; Cmax (4.1 to 20.8 ng · ml−1; AUC (0–24) 20 to 132 ng · ml−1 · h (1 and 5 mg respectively) increased progressively with dose indicating dose dependent kinetics; no significant changes occurred in the visual analogue scale for sedation. A comparison of alfuzosin 5 mg, prazosin 1 mg and placebo each administered for 4 days, indicated that alfuzosin did not significantly reduce standing SBP on either Day 1 or Day 4; prazosin reduced SBP at 2 and 4 h on Day 1 and 6 h on Day 4 compared to placebo. Standing HR was increased by alfuzosin at 2 h on Day 1 and Day 4; increases occurred with prazosin at 2, 4, 6 and 8 h on Day 1 and 6 h on Day 4. Supine plasma noradrenaline increased with alfuzosin and prazosin at 2 and 4 h on Days 1 and 4; the increases were not significantly different. The plasma elimination half-life (t1/2) for alfuzosin was 3.4 h and 3.1 h after acute and chronic administration; (t1/2) for prazosin was 2.6 and 2.9 h. In conclusion alfuzosin causes small reductions in systolic blood pressure, accompanied by a dose dependent increase in heart rate in the supine and standing position and following exercise.
    Type of Medium: Electronic Resource
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