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  • Articles  (71)
  • healthy volunteers  (71)
  • Springer  (71)
  • Annual Reviews
  • National Academy of Sciences
  • 1985-1989  (71)
  • 1965-1969
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  • Articles  (71)
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  • Springer  (71)
  • Annual Reviews
  • National Academy of Sciences
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  • 1
    Electronic Resource
    Electronic Resource
    Methylprednisolone versus prednisolone pharmacokinetics in relation to dose in adults (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 323-329 
    Details
    ISSN: 1432-1041
    Keywords: methylprednisolone ; prednisolone ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition and plasma binding of methylprednisolone were examined in seven normal volunteers following the administration of 5, 20 and 40 mg of intravenous methylprednisolone sodium succinate. Methylprednisolone exhibits linear plasma protein binding averaging 77%. The mean plasma methylprednisolone clearance of 337 ml·h−1. kg−1 was independent of dose. The steroid appears to moderately distribute into tissue spaces with a mean volume of distribution of 1.41·kg−1. Methylprednisolone disposition parameters were compared with the non-transcortin bound parameters for prednisolone. The prednisolone plasma clearance based on the transcortin free-drug is similar to methylprednisolone total plasma clearance. However, the corrected volume of distribution of prednisolone is only one-half that of methylprednisolone. The disposition rate of these two steroids is thus similar, in spite of their metabolic control by different enzymatic pathways and major influence of saturable transcortin binding on prednisolone elimination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00541537
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  • 2
    Electronic Resource
    Electronic Resource
    Interaction of oxaprozin with acetaminophen, cimetidine, and ranitidine (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 371-374 
    Details
    ISSN: 1432-1041
    Keywords: oxaprozin ; drug interaction ; acetaminophen ; cimetidine ; ranitidine ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twelve healthy male volunteers participated in a single-dose four-way crossover study to evaluate potential drug interactions with oxaprozin, a nonsteroidal antiinflammatory agent of the propionic class. The four modes of administration were:a. oxaprozin, 1200 mg alone;b. oxaprozin during concurrent acetaminophen, 500 mg 4 times daily;c. oxaprozin with cimetidine, 300 mg 4 times daily;d. oxaprozin with ranitidine, 150 mg every 12 hours. Acetaminophen, cimetidine, or ranitidine were begun 24 hours prior to oxaprozin dosage and continued for the 10-day duration of each trial. No significant differences existed among the four treatment conditions in peak plasma oxaprozin concentration (86 µg/ml), volume of distribution (0.23 l/kg), time of peak concentration (3.7 h after dosage), or elimination half-life (54 h). Oxaprozin oral clearance was significantly lower (by 20%) during both the cimetidine and ranitidine trials versus control (0.047 vs 0.047 vs 0.059 ml/min/kg), but clearance during acetaminophen was not significantly different from control. Thus acetaminophen, cimetidine or ranitidine has only a small influence on the pharmacokinetics of a single oral dose of oxaprozin. The reduction in oxaprozin clearance due to cimetidine or ranitidine is statistically significant but small in magnitude.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00981141
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of a stable prostaglandin analogue, L-644,122, in healthy and hypertensive men (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 685-688 
    Details
    ISSN: 1432-1041
    Keywords: prostaglandin analogue ; renal function ; vasodilator ; L-644,122 ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary L-644,122 is a chemically stable vasodilator prostaglandin analogue. It is a selective renal vasodilator in dogs. The object of the present study was to determine whether it increases effective renal plasma flow (ERPF) in man. L-644,122 was administered intravenously to 4 healthy volunteers and by mouth to 4 mild hypertensives. It did not increase ERPF. Instead it acted as a non-specific vasodilator, lowering diastolic blood pressure and increasing heart rate. An unexpected increase in glomerular filtration rate (19% greater than placebo) after low dose intravenous L-644,122 merits further study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607916
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of concomitant food intake on absorption kinetics of fenoldopam (SK&F 82526) in healthy volunteers (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 103-106 
    Details
    ISSN: 1432-1041
    Keywords: fenoldopam ; peripheral dopamine agonist ; pharmacokinetics ; absorption ; food effects ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight healthy volunteers participated in an open crossover study to assess the effect of a standardised meal on the systemic availability of a single oral dose of fenoldopam mesylate 100 mg. Subjects were studied on four separate occasions, twice fasting and twice fed in randomised, balanced order. Plasma and urine samples were obtained before and at regular intervals up to 25 h post dose. Measurement of fenoldopam (SK&F 82526) and its 8-sulphate metabolite (SK&F 87782) were by means of HPLC-EC analysis. Area under the plasma concentration time curve (AUC) and maximum detected plasma concentration (Cmax) for fenoldopam and SK&F 87782 were significantly reduced whereas time to maximum concentration was significantly increased with food. Using AUC's for fenoldopam and SK&F 87782, mean relative bioavailabilities were 35% and 81% respectively under fed compared with fasting conditions. Twenty-four hour excretion of fenoldopam was significantly reduced with food, but excretion of SK&F 87782 was apparently unchanged. Mean relative bioavailabilities calculated from these data were 83% and 86% respectively. Relatively large inter-subject variability in AUC and Cmax were seen, but intra-subject variability was not marked. Mild symptoms associated with vasodilation were reported on all study days.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609968
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetic-pharmacodynamic modelling of oxprenolol in man using continuous non-invasive blood pressure monitoring (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 395-400 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542442
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  • 6
    Electronic Resource
    Electronic Resource
    Effect of short-term omeprazole administration of serum pepsinogens in relation to fasting serum gastrin and gastric acid secretion (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 345-349 
    Details
    ISSN: 1432-1041
    Keywords: omeprazole ; pepsinogen A ; pepsinogen C ; fasting serum gastrin ; pentagastrin ; gastric-acid ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A study has been done in 10 male healthy volunteers of the effect of oral omeprazole 20 mg daily for 3 days on the serum concentrations of Pepsinogens A and C in relation to changes in fasting serum gastrin and basal and pentagastrin stimulated gastric acid output. The concentrations of Pepsinogens A and C showed concomitant and variable but significant increases, and the Pepsinogen A, C ratio did not change during the 3-day course of omeprazole. The increments were also significantly correlated with the increase in fasting serum gastrin and with the reduction in pentagastrin stimulated acid output. The correlations were mainly due to the marked inhibition of gastric acid secretion and the corresponding increases in serum gastrin and Pepsinogens A and C in two subjects, as in the other 8 subjects the changes were only modest. There appears to be a relationship, therefore, between the degree of inhibition of acid by omeprazole and the parallel increases in both serum pepsinogens and fasting gastrin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558498
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  • 7
    Electronic Resource
    Electronic Resource
    The pharmacokinetics after intravenous and oral administration in man of theα 2-adrenoreceptor antagonist idazoxan (RX781094) (1986)
    Springer
    European journal of clinical pharmacology 29 (1986), S. 743-745 
    Details
    ISSN: 1432-1041
    Keywords: idazoxan ; pharmacokinetics ; alpha 2-adrenoceptor antagonist ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A high performance liquid chromatographic method was developed for the quantitative determination of idazoxan in plasma. The assay was used to study the disposition of the drug after intravenous infusion and oral administration to five normal subjects. After i.v. administration the kinetics could be described by a two compartment model with a mean elimination half life of 4.20 h. The mean calculated volume of distribution during the elimination phase was 3.20 l/kg−1 and the mean plasma clearance was 824 ml min−1. After oral administration a lag period before onset of absorption was observed in all five volunteers, the plasma levels declining monoexponentially from the peak concentration with a mean elimination half life of 5.58 h. The absolute availability varied between 26% and 41% with a mean value of 34%. Invitro measurements produced a blood/plasma ratio of 1.3 for idazoxan.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00615972
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  • 8
    Electronic Resource
    Electronic Resource
    Hypotensive effects of ovine and human corticotrophin-releasing factors in man (1987)
    Springer
    European journal of clinical pharmacology 31 (1987), S. 531-534 
    Details
    ISSN: 1432-1041
    Keywords: corticotrophin-releasing factor ; hypotension ; ovine CRF ; human CRF ; healthy volunteers ; tachycardia ; plasma noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effects of i.v. bolus injections of 100 and 200 µg ovine CRF and human CRF in man have been compared. Neither ovine CRF 100 µg nor human CRF 100 µg caused a significant change in blood pressure, although the pulse rate was increased in all the subjects tested. The mean maximum increase in pulse rate after human CRF was almost twice that after ovine CRF (21 vs 12 beats·min−1;p〈0.05). After 200 µg ovine CRF in all subjects the diastolic blood pressure declined gradually from 77 mm Hg to a nadir of 67 mm Hg at 22 min (p〈0.002). After 200 µg human CRF diastolic blood pressure fell from 78 mm Hg to a nadir of 61 mm Hg at 6 min (p〈0.002); the fall after human CRF was significantly greater than after ovine CRF (p〈0.05). After 200 µg ovine CRF there was a slight increase in pulse rate lasting for 6 min, and after 200 µg human CRF there was a marked (reflex) tachycardia for 30 min. Only after the highest dose of human CRF did a slight increase in systolic blood pressure occur. The haemodynamic effects of both doses of human CRF were accompanied by significant increases in plasma noradrenaline concentrations, which were significantly greater after the higher dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606625
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  • 9
    Electronic Resource
    Electronic Resource
    Effect of 40749 RP on basal and sham feeding stimulated gastric secretion in man (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 479-482 
    Details
    ISSN: 1432-1041
    Keywords: 40749 RP ; gastric acid secretion ; gastric antisecretory agent ; sham feeding ; healthy volunteers ; vagal stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 40749 RP, a pyridyl-2-tetrahydrothiophene derivative, is known to be a potent inhibitor of the gastric acid response to pentagastrin, betazole and a meal. In 6 healthy young volunteers, a single oral dose of 2 mg · kg−1 greatly reduced the gastric acid secretory response to sham-feeding. By contrast, neither gastric pepsin nor the plasma PP response were altered by the drug. No change was observed in plasma gastrin, motilin, VIP or somatostatin concentrations. The results show that 40749 RP is also active on the pure vagus-stimulated gastric acid secretion. The lack of effect upon gastric pepsin and plasma PP suggests that 40749 RP is not likely to act on the basolateral cholinergic receptor and that it affects further cellular steps involved in hydrogen ion secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544239
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  • 10
    Electronic Resource
    Electronic Resource
    Effect of antipyrine coadministration on the kinetics of acetaminophen and lidocaine (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 413-417 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561374
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