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  • healthy volunteers  (14)
  • Springer  (14)
  • Elsevier
  • Nature Publishing Group
  • 1985-1989  (14)
  • 1955-1959
  • 1988  (14)
  • 1957
Collection
Publisher
  • Springer  (14)
  • Elsevier
  • Nature Publishing Group
Years
  • 1985-1989  (14)
  • 1955-1959
Year
  • 1
    ISSN: 1432-1041
    Keywords: oxprenolol ; beta-blockade ; concentration-effect relationship ; non-invasive monitoring ; exercise test ; blood pressure monitoring ; healthy volunteers ; predictive model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relationship between the plasma concentration of oxprenolol and its haemodynamic effects during physical exercise was studied in 6 healthy volunteers, in whom BP and heart rate (HR) were continuously monitored by non-invasive techniques (Fin-A-Press-Tonometer) during repeated three-minute exercise periods for 8 h after treatment. Using the fitted pharmacokinetic curve, the drug effect was related to its plasma concentration using the Emax model. The mean EC50 for the relationship between drug concentration and heart rate during exercise (HRex) was 73.1 ng/ml, and for systolic blood pressure during exercise (SBPex) it was 112.7 ng/ml. Emax was 29.0% for HRex, and 33.2% for SBPex. There were no consistent differences between the parameters for the effects on HRex and SPBex. Thus, using a new, non-invasive technique for continuous measurement of blood pressure, the effect of a beta-adrenoceptor blocking drug on SBPex was described with similar accuracy as its effect on HRex.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 35 (1988), S. 413-417 
    ISSN: 1432-1041
    Keywords: antipyrine ; acetaminophen ; lidocaine ; drug interactions ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic interactions between antipyrine and acetaminophen were evaluated in 7 healthy volunteers. On 3 occasions subjects received:1, antipyrine 1.0 g intravenously (i.v.);2, acetaminophen 650 mg i.v.;3, antipyrine 1.0 g and acetaminophen 650 mg i.v. simultaneously. Between Trials 1 and 3, antipyrine elimination t1/2 (17.2 vs 17.4 h), clearance (0.44 vs 0.43 ml·min−1·kg−1) and 24-h recovery of antipyrine and metabolites (313 vs 293 mg) did not differ significantly. Between Trials 2 and 3, acetaminophen Vz was reduced (1.14 vs 1.00 l·kg−1), t1/2 prolonged (2.7 vs 3.3 h), clearance reduced (4.8 vs 3.6 ml·min−1·kg−1), and fractional urinary recovery of acetaminophen glucuronide reduced. Eight additional subjects received 50 mg of lidocaine hydrochloride i.v. in the control state, and on a second occasion immediately after antipyrine 1.0 g given i.v. The two trials did not differ significantly in lidocaine Vz (2.6 vs 2.7 l·kg−1), t1/2 (2.0 vs 2.4 h) or clearance (15.0 vs 13.5 ml·min−1·kg−1). Although acetaminophen does not alter antipyrine kinetics, acute administration of antipyrine appears to impair acetaminophen clearance, possibly via inhibition of glucuronide formation. However, antipyrine has no significant effect on the kinetics of a single i.v. dose of lidocaine.
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  • 3
    ISSN: 1432-1041
    Keywords: cimetidine ; ramixotidine ; prolactin ; testosterone ; 17 beta-estradiol ; H2-receptors ; CM 57755A ; gastrin ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Three groups of eight healthy male volunteers received placebo for 2 days, then daily morning doses either of cimetidine 800 mg, ramixotidine 750 mg (CM 57755A), or placebo, for 14 days, and then were all returned to placebo for one more day. Plasma levels of prolactin, testosterone and 17β-estradiol were measured on Days 2, 3, 16 and 17 in blood samples taken 30 and 15 min before and 0, 60, 120, 180, 240 and 300 min after treatment. Gastrin was assayed in blood collected on the same days 180 min after treatment. Mean pre- and post-treatment areas under the time-concentration curves of the first three hormones were not significantly different in the three groups on any test day, or within the same group throughout the four test days. Mean plasma gastrin levels ranged between 27 and 42 pg/ml, respectively, in the placebo and cimetidine treated groups on test day 3, and intermediate values were found in the group receiving CM 57755A. There was no statistically significant difference in gastrin level between the groups on any test day or within the same group throughout the four test days. No subjective side-effects attributable to the treatments were reported, and there were no abnormalities in blood pressure, heart rate or standard laboratory tests.
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  • 4
    ISSN: 1432-1041
    Keywords: BW443C ; enkephalin ; opioid peptide ; healthy volunteers ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied 16 healthy men to evaluate preliminary pharmacodynamics and kinetics of BW443C given by i.v. infusions. Four volunteers received escalating doses at weekly intervals, starting at 0.1 µg·kg−1 for 60 min and increasing to a maximum of 2.0 µg·kg−1·min−1 for 180 min. Subsequently 12 different subjects received single i.v. infusions of 10 µg·kg−1·min−1 for 20 min. Subjective effects were reported and objective measurements made of central nervous and cardiovascular effects. Blood was sampled at intervals on all occasions, plasma concentrations were determined by radioimmunoassay and pharmacokinetic profiles were analysed using NONLIN. Dry mouth and some nasal stuffiness were reported and postural hypotension occurred in 5/16 subjects at plasma concentrations 〉0.8 µg·ml−1. Supine blood pressure was well maintained in all subjects and hypotension resolved within 60–90 min of discontinuing the infusion. There was no evidence of sedation, mood change, nausea, vomiting, miosis, change in accomodation or respiratory depression. Rapid infusions produced transient feelings of warmth, heavy eyelids, heavy legs, and increased bowel sounds, which resolved despite increasing plasma concentrations. The disposition of the peptide was adequately described by a 2-compartment model with a mean ± SD plasma clearance of 123±18 ml·min−1 and a half-life of 2.0±0.4 h.
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  • 5
    ISSN: 1432-1041
    Keywords: metronidazole ; cimetidine ; pharmacokinetics ; drug interaction ; drug metabolism ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time course of the effect of cimetidine on the pharmacokinetics of metronidazole was investigated in 6 healthy volunteers. Cimetidine 1.0 g/day was administered for 9-days and metronidazole 500 mg was administered orally on the second and eighth days, and in a control experiment. During cimetidine treatment the plasma kinetics of metronidazole and its partial clearance by renal excretion of the unchanged compound, glucuronidation, hydroxylation and oxidation to its acetic acid metabolite were not significantly different from the control values. The results indicate that cimetidine does not influence the pharmacokinetics or metabolism of a single oral dose of metronidazole.
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  • 6
    ISSN: 1432-1041
    Keywords: acetaminophen ; codeine ; clearance ; metabolite formation ; glucuronidation ; pharmacokinetics ; healthy volunteers ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In nine healthy volunteers, the clearance and metabolism of acetaminophen 1000 mg i.v. was evaluated with and without two concomitant oral doses of codeine in order to investigate a possible interaction. Plasma acetaminophen was followed for 720 min and urine was collected for 24 h after each dose for determination of metabolites. When codeine was coadministered, the average total clearance of acetaminophen and its clearance by glucuronidation, sulphation and mercapturate formation were 0.58 to 1.12-times the control values. It is concluded that therapeutic doses of codeine do not influence the clearance or metabolism of acetaminophen.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 35 (1988), S. 237-240 
    ISSN: 1432-1041
    Keywords: platelet activating factor (PAF) ; WEB 2086 ; platelet aggregation ; PAF-antagonist ; dose response ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary WEB 2086 is a novel PAF-acether antagonist, whose pharmacological action in man has only been preliminarily defined. Twelve healthy male volunteers received oral doses of 5, 30 and 90 mg and over the following 24 h inhibition of 5 × 10−8 M PAF-acether-induced platelet aggregation ex vivo was studied as an indicator of pharmacological activity. WEB 2086 inhibited PAF-acether-induced platelet aggregation in all the doses tested, with the maximum effect 1 to 2 h after administration. After 2 h 5- 30- and 90-mg doses caused, respectively, 87, 98 and 100% inhibition. The magnitude and duration of the inhibitory effect was dose-dependent, with a significant action still detectable 10 h after administration of all three doses, and 12 h after administration of the two highest doses (30 and 90 mg). The subjects did not complain of any significant adverse effect and all completed the study.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 35 (1988), S. 371-377 
    ISSN: 1432-1041
    Keywords: ACTH 4-10 ; radioimmunoassay ; plasma extraction ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A specific radioimmunoassay for the quantitative measurement of ACTH 4-10 and a procedure for its extraction from plasma have been developed. Its pharmacokinetics was studied in eight healthy male volunteers given ACTH 4-10 125 µg/kg body weight as a bolus i.v. injection, by infusion and intranasally. Following the i.v. bolus, plasma levels rapidly declined biexponentially, with half-lives of 0.39±0.05 min for the α-phase and 3.84 ± 1.5 min for the β-phase (mean±SD). The constant rate i.v. infusion yielded steady-state levels between 0.74 and 5.06 ng/ml plasma. Administered as intranasal spray, absorption of intact ACTH 4-10 was low and variable (maximal bioavailability 7.6%). The results are discussed in relation to the dose-dependent effects of ACTH 4-10 on the auditory evoked potential.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 35 (1988), S. 563-566 
    ISSN: 1432-1041
    Keywords: tenoxicam ; pharmacokinetics ; elderly ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fourteen elderly subjects (10 women, 4 men) with a mean age of 81 (SD 6.7) years and in need of anti-inflammatory drug treatment were given a single dose of 20 mg tenoxicam. After a drug-free interval of 5 weeks, multiple dose treatment with 20 mg tenoxicam once daily for 56 days was initiated. The single and multiple dose kinetics of tenoxicam were investigated after HPLC determination of tenoxicam in the plasma. The elimination half-life of tenoxicam ranged from 44 to 132 h (mean 71.9 h) with no significant difference between the single and multiple dosage regimens. Tenoxicam reached maximum plasma concentrations after 1.4 and 1.1 h, with values of 3.6 and 15.5 µg·ml−1, for the single and multiple dosage regimen respectively. The corresponding trough values (24-h values) were 1.8 and 11.7 µg·ml−1. A mean accumulation ratio of 5.1 was calculated. The mean increase in the area under the plasma concentration time curves at steady-state was 21% more than predicted from the initial single dose. This deviation from linearity was considered to be of minor clinical significance. The kinetics of tenoxicam in elderly were similar to that published for young healthy volunteers.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 35 (1988), S. 607-612 
    ISSN: 1432-1041
    Keywords: propranolol ; atenolol ; baroreflex function ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute administration of the β-adrenoceptor antagonists propranolol (80 mg) and atenolol (50 mg) on baroreflex function were investigated in healthy volunteers. Two h after administration both propranolol and atenolol significantly prolonged the supine R-R interval (1126, 1128 ms respectively) compared to placebo (1012 ms); systolic arterial pressure also fell (102.9, 102.0 mm Hg respectively) compared to placebo (112.6 mm Hg). Baroreflex function, assessed using glyceryl trinitrate to deactivate the baroreceptors was unchanged by these drugs compared to placebo. Baroreflex sensitivity (slope of the linear regression line relating R-R interval to systolic blood pressure) using phenylephrine to activate the baroreceptors, was also unchanged (17.2, 17.9 ms/mm Hg respectively) compared to placebo (19.9 ms/mm Hg). However both regression lines were shifted (p〈0.05) to the left compared to placebo.
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