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  • 1
    Publication Date: 2019-06-28
    Description: The fragmentation of a 225 MeV/n O-16 beam was investigated at the Bevalac. Preliminary cross sections for mass = 13, 14, 15 fragments are used to constrain the nuclear excitation functions employed in galactic propagation calculations. Comparison to cosmic ray isotonic data at low energies shows that in the cosmic ray source C-13/C approximately 2% and N-14/0=3-6%. No source abundance of N-15 is required with the current experimental results.
    Keywords: SPACE RADIATION
    Type: OG-4.3-2 , 19th Intern. Cosmic Ray Conf - Vol. 2; p 80-83; NASA-CP-2376-VOL-2
    Format: application/pdf
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  • 2
    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha1-adrenoceptor inhibitor ; elderly patients ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The α1-adrenoceptor antagonist doxazosin has been compared with placebo in 40 elderly hypertensive patients (mean age 71.4 years). At the end of 10 weeks once daily treatment with doxazosin the mean 24-h post-dose changes in standing and supine blood pressure compared with placebo were −6.9/−5.6 mmHg (systolic/diastolic) and −6.2/−5.5 mmHg respectively. The reductions in standing and supine diastolic blood pressures were statistically significant compared with placebo. At the end of treatment steady-state pharmacokinetics were evaluated in 18 patients. The plasma elimination half-life during the dose interval in these patients was 16.1 h (range 10.1–27.1 h) and the median time to peak plasma concentration was 3 h (range 1–4 h). One patient was withdrawn because of adverse effects (headache, weakness, and sweating) during doxazosin treatment. Once daily doxazosin reduced diastolic blood pressure and was well tolerated in these elderly hypertensive patients.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 34 (1988), S. 151-156 
    ISSN: 1432-1041
    Keywords: ceftriaxone ; probenecid ; drug interaction ; protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics and binding parameters of ceftriaxone have been characterized in eight normal subjects who received, in sequence, 1.0 g ceftriaxone and 1.0 g ceftriaxone together with 250 and 500 mg probenecid q.i.d. Probenecid increased the total systemic clearance (CL S T ) from 0.244 to 0.312 ml/min/kg, whereas the terminal half-life (t 1/2(β) T ) fell from 8.1 to 6.5 h. In contrast, the renal clearance of free ceftriaxone (CL R F ) was decreased from 2.09 to 1.67 ml/min/kg, confirming a small but significant contribution of tubular secretion to the renal elimination of ceftriaxone. The final value of CL R F was attained with the lower dose probenecid, whereas the non-renal clearance of free ceftriaxone (CL NR F ) fell progressively from 2.78 to 1.90 ml/min/kg with the increasing probenecid dose. The total decrease in the systemic clearance of free ceftriaxone (CL S F ) after the higher dose of probenecid was about 30% (4.87 to 3.57 ml/min/kg). As a consequence of a decreased affinity constant (KA), the average free fraction in plasma (f) was increased by 54% after the low dose and by 74% after the high dose of probenecid. The protein binding interaction between probenecid and ceftriaxone appears to be unique. The results are of limited clinical consequence for ceftriaxone but they emphasise the importance of evaluating the kinetics of the free drug when examining interactions involving probenecid.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: ipratropium bromide ; radioceptor assay ; pharmacokinetics ; inhalation ; systemic administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single doses of ipratropium bromide were administered intravenously, orally and by slow inhalation to ten healthy male volunteers. The plasma level after oral administration followed a low but broad plateau persisting for several hours. After i.v. administration the kinetic parameters were: Vc=25.9 l, Vα=13.1 l, Vβ=338 l, $$t_{{1 \mathord{\left/ {\vphantom {1 {2_\alpha }}} \right. \kern-\nulldelimiterspace} {2_\alpha }}} = 3.85\min $$ , $$t_{{1 \mathord{\left/ {\vphantom {1 {2_\beta }}} \right. \kern-\nulldelimiterspace} {2_\beta }}} = 98.4\min $$ , AUC=15.0 h · ng/ml, kel=11.8 l/h and total clearance is 2325 ml/min. The bioavailability was 3.3% (range 0.9–6.1%) on comparing the plasma AUCs following i.v. and 20 mg oral administration. The cumulative renal excretion (0–24 h) after i.v. administration was compared with that after oral administration and inhalation. Following oral administration, the apparent systemic availability was around 2%, and after inhalation it was 6.9%. In comparison with oral placebo administration, only after i.v. administration was there a significant change in heart rate (from 63.7 to 90.2 beats/min). The systolic blood pressure rose from 115.1 to 119.6 mm Hg and the diastolic blood pressure from 68.3 to 78.3 mm Hg.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: benazepril ; furosemide ; converting enzyme inhibitor ; pharmacokinetics ; drug interaction ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single oral doses of 10 mg converting enzyme inhibitor benazepril (CGS 14824A) and 40 mg furosemide were administered to 12 healthy male volunteers either separately or concomitantly. The pharmacokinetic parameters of benazepril were not influenced by coadministration of furosemide. Urinary excretion of total furosemide was significantly reduced by 10 to 20% in the presence of benazepril. This effect was considered clinically insignificant. Erect blood pressure decreased and pulse rate increased only during concomitant treatment.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 29 (1986), S. 721-723 
    ISSN: 1432-1041
    Keywords: domperidone ; levodopa ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of simultaneous oral administration of 20, 40, or 80 mg domperidone on the pharmacokinetics of an oral 500 mg dose of levodopa was studied in eight normal women. No significant differences in maximum plasma levodopa concentration, the time of its attainment, or the area under the plasma levodopa concentration versus time profile occurred. Domperidone significantly reduced the incidence of adverse gastrointestinal effects due to levodopa administration.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1041
    Keywords: captopril ; uraemia ; captopril disulfide ; dialysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have measured the plasma concentrations of captopril and total disulfide conjugates of captopril after a 50 mg oral dose in 6 uraemic patients on maintenance dialysis and in 8 hypertensive subjects with normal renal function. The mean peak plasma concentration of captopril was 2.5 times higher (0.447 µg·ml−1 vs 0.181 µg·ml−1) and the concentrations of the disulfides 4 times higher (3.62 µg·ml−1 vs 0.924 µg·ml−1) in the uraemic patients. Moreover captopril disulfide conjugates in the uraemic subjects reached peak concentrations at 8 h after the dose and subsequently felt. The apparent plasma half-time was 46±19 h. Only 15% of these conjugates were removed by dialysis. This marked accumulation of captopril conjugates was associated with a sustained fall in both systolic and diastolic blood pressures. In uraemic patients the mean maximum reduction in systolic and diastolic blood pressures were 37±7 mmHg and 24±9 mmHg respectively, occurring 6 h after the dose, compared with 8±7 and 8±1 mmHg respectively at 30 min in normal renal function patients. These results are consistent with the results of animal experiments, which show that captopril disulfides can be converted back to free captopril and can contribute to the antihypertensive effect of the drug. They provide a reationale for reducing the dose and frequency of administration of captopril in patients with significant renal impairment.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 31 (1986), S. 239-242 
    ISSN: 1432-1041
    Keywords: piroximone ; cardiotonic drug ; pharmacokinetics ; bioavailability ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six healthy, male subjects received single intravenous and oral doses of piroximone. Plasma piroximone concentrations were assayed up to 8 h after each dose by HPLC. Urinary excretion of the parent compound was also determined. Following the oral dose, piroximone reached peak plasma concentrations within 30 to 90 min. The t1/2 of the terminal decay phase was 2.8 h, the mean apparent volume of distribution was 2.5 l/kg, and the mean total body clearance was 755 ml/min. Mean urinary recovery of parent drug within 24 h was 50% after the intravenous dose and 41% after the oral dose. Renal clearance accounted for approximately 50% of total body clearance. Oral bioavailability, estimated from AUC or urinary recovery, was 80%.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 45-51 
    ISSN: 1432-1041
    Keywords: disopyramide ; myocardial infarction ; antiarrhythmic agent ; pharmacokinetics ; protein binding ; intravenous administration ; oral administration ; gastro-intestinal absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To study the effects of acute myocardial infarction on the pharmacokinetics of disopyramide a single oral dose of disopyramide base (200 mg) was administered to 6 patients with myocardial infarction both in the acute (Study I) and recovery (Study II) phases. An intravenous tracer dose of14C-disopyramide (2.5 µg/0.3 mg) was given simultaneously with the oral dose. On the basis of the intravenous tracer data, the volume of distribution, binding to plasma proteins, total plasma clearance, renal clearance and elimination half-life of disopyramide and mono-N-dealkyl disopyramide were the same in Studies I and II. The peak serum concentrations of disopyramide after oral dosing in Studies I and II were 2.6±1.2 (SEM) and 6.4±1.9 µg/ml, respectively (p〈0.05), the peak times 3.29±1.22 and 1.21±0.39 h (N.S.) and the AUCINF 38.0±7.7 and 60.7±9.9 µg·h·ml−1 (p〈0.05). The recovery of disopyramide in urine over 3 days averaged 46% and 47% of dose, and that of mono-N-dealkyl disopyramide 22% and 16% of the dose, respectively. Thus, the gastrointestinal absorption of disopyramide was disturbed, resulting in low plasma concentrations after oral dosing, whereas the elimination of disopyramide was unaltered in the acute phase of myocardial infarction.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 31 (1987), S. 583-588 
    ISSN: 1432-1041
    Keywords: cotinine ; pharmacokinetics ; non-smokers ; absolute bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cotinine, the main metabolite of nicotine, was administered intravenously to healthy male non-smoking volunteers in doses of 5, 10 and 20 mg, and orally in doses of 10 and 20 mg. Intravenous administration was characterized by a dose-independent half-life of 12.2 h, mean residence time of 15.9 h, total clearance of 3.64 l h−1 and a volume of distribution of 56.5 l. Renal clearance was 0.46 l h−1 and approximately 12.0% of the dose was excreted unchanged in the urine. The mean absorption time after oral dosing ranged between 1 and 3 h, the peak concentration was reached within 45 min and the mean elimination half-lives were 12.9 and 11.7 h, respectively, after the 10 and 20 mg doses. Systemic bioavailability ranged between 0.84 and 1.11 following 10 mg and between 0.97 and 1.03 following the 20 mg dose. Mean urinary recovery and renal clearance were almost identical with the values after iv administration.
    Type of Medium: Electronic Resource
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