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  • healthy volunteers  (85)
  • Springer  (85)
  • Oxford University Press
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  • Springer  (85)
  • Oxford University Press
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 46 (1994), S. 23-28 
    ISSN: 1432-1041
    Keywords: Atenolol ; Captopril ; Central effects ; short term administration ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The central effects of atenolol (50 mg tds) and captopril (50 mg tds) ingested for a period of seven days were studied in ten healthy volunteers. A placebo and two active control drugs, methyldopa (250 mg tds) and oxazepam (10 mg), were included in the design. Oxazepam was ingested on the seventh day only, with a placebo being taken on the preceding six days. On the seventh day, central effects of the drugs were tested at 10.00–11.00 h (session 1), immediately before the subjects' last dose of each drug and at 2.5–3.5 h after the final dose of each drug (1330–1430 h, session 2). Performance was assessed using digit symbol substitution, continuous attention, letter cancellation, choice reaction time, finger tapping, immediate and short-term memory, critical flicker fusion and two flash fusion. Subjects assessed their mood and well-being on a series of 12 visual analogue scales. Recordings of the EEG and body sway were carried out. Neither atenolol nor captopril altered performance at any of the skills tested. There were no effects on subjectively assessed alertness or mood with captopril, while atenolol significantly increased wakefulness in session 2 and when the two sessions were meaned. Similarly, captopril did not modify body sway, while with atenolol there was a significant decrease in activity in the frequency range 1.0–2.75 Hz from session 1 to session 2. Both captopril and atenolol modified the electrical activity of the brain, with captopril increasing delta and theta activity and atenolol reducing delta, alpha and beta activity. Methyldopa significantly increased the number of involuntary rest pauses in the finger tapping task, and the choice reaction time from session 1 to session 2. There was a decrease in passivity during the first session and an increase in wakefulness in session 2 with methyldopa. This drug also decreased body sway in the frequency range 1.0–2.75 Hz activity in session 2, while oxazepam decreased bodys was at 1.0 to 2.75 Hz and increased activity at 2.5–3.0 Hz in session 2. Oxazepam reduced delta, theta and alpha content of the EEG. The present study has been unable to demonstrate any development of adverse central effects with captopril over a period of 7 days of drug ingestion. With atenolol adverse effects were present following short term dosing but were not more pronounced than with acute ingestion seen in previous studies. However effects on the electrical activity of the brain with atenolol remained after 7 days suggesting that the changes reported previously with single ingestions do not disappear.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 659-664 
    ISSN: 1432-1041
    Keywords: BTS 49465 ; hypertension ; pharmacokinetics ; blood pressure effect ; heart rate effect ; side-effects ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic and haemodynamic effects of a 200 mg oral dose of BTS 49465 (7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone) were investigated in a double-blind placebo controlled study. BTS 49465 was rapidly absorbed and cleared from the systemic circulation with a half-life of 1.6 h by oxidation to the sulphone metabolite. The metabolite was cleared with a half-life of 37.6 h. Saliva concentrations of both BTS 49465 and its metabolite correlated well with the plasma concentrations. Compared to placebo, BTS 49465 produced statistically significant reductions in blood pressure and increases in heart rate both supine and after a 60° head up tilt. The time course of the haemodynamic changes suggested that the sulphone metabolite contributed to the overall hypotensive response. Plasma Renin Activity was only marginally elevated and there was no evidence of acute fluid retention. BTS 49465 was well tolerated in terms of haematological and biochemical parameters and subjective side-effects.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1984), S. 447-452 
    ISSN: 1432-1041
    Keywords: alaproclate ; antipyrine clearance ; serotonin reuptake inhibitor ; healthy volunteers ; antipyrine metabolism ; metabolite clearance ; alaproclate kinetics ; inhibition of drug metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Alaproclate, a selective serotonin reuptake inhibitor, presently undergoing clinical trial for the treatment of major depressive disorders, has been shown to inhibit hexobarbital metabolism in mice. In the present study the influence of oral alaproclate on the total plasma clearance of antipyrine and on the formation of its metabolites was investigated in 10 healthy volunteers. The peak level of alaproclate was reached after about 1.5 h, and after a distribution phase, its plasma elimination half-life was between 3.0 and 3.5 h. Antipyrine tests were performed before treatment, during the first four doses and after the seventh dose of alaproclate 200 mg/day. During treatment, total plasma antipyrine clearance and the clearance for production of all antipyrine metabolites were reduced by 30%, indicating non-selective inhibition of oxidative drug-metabolizing enzyme activity in man by alaproclate. After the last dose of alaproclate, antipyrine plasma clearance and the clearance to its metabolites returned to control values. In order to allow more detailed evaluation of the results, the time course of the clearances for production of metabolites was investigated. This revealed that the extent of inhibition of metabolite formation by alaproclate was dependent on the plasma alaproclate level, indicating a rapidly reversible inhibition.
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  • 4
    ISSN: 1432-1041
    Keywords: renin ; aldosterone ; dopamine ; natriuretic hormone ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute natriuretic effect of human atrial natriuretic peptide (ANP) has been well described in man. We have now studied possible hormonal mediators of this effect. We studied six healthy volunteers on two occasions when they received either an infusion of ANP of 1.5 pmol·kg−1·min−1 for 30 min followed by 15 pmol·kg−1·min−1 for a further 30 min, or matching vehicle infusions in a randomized single-blind fashion. On the placebo day, plasma renin activity (PRA) rose from 1.26±0.08 to 1.57±0.14 ng A1·ml−1·h−1, while on the ANP study day PRA fell from 1.45±0.15 to 1.28±0.05 ng A1·ml−1·h−1 (p〈0.01). No significant changes were found in plasma aldosterone concentrations or in urinary dopamine excretion. These results provide evidence that ANP suppresses renin release in man.
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  • 5
    ISSN: 1432-1041
    Keywords: Felodipine ; Nitrendipine ; Nifedipine ; enantiomers ; blood pressure ; heart rate ; concentration-effect relationship ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of racemic (rac) felodipine, rac-nitrendipine and nifedipine (all 20 mg solution p.o.) on non-invasively measured blood pressure and heart rate were investigated in a randomised, double-blind, cross-over study in 12 normotensive, young, healthy males. Compared to baseline values, heart rate increased more after rac-felodipine treatment (+47% at maximum) than rac-nitrendipine (+40%) and nifedipine (+38%); only small and variable changes in blood pressure were observed with any of the drugs. The baseline-corrected area under the heart rate-time curve up to 4 h after the administration of rac-felodipine was 197% and 180% larger than after nifedipine and rac-nitrendipine treatment, respectively. The effects on heart rate could be fitted individually to a sigmoidal Emax-model without hysteresis for all drugs under investigation. The relative potencies of the unbound drugs for their indirect effects on heart rate were 1:7:43 for nifedipine, rac-nitrendipine and rac-felodipine, respectively. The active (S)-enantiomers of felodipine and nitrendipine appeared to be 9-and 60-times as potent as nifedipine in this respect, assuming no (inter)activity of the (R)-enantiomers. Individual and mean changes in blood pressure were small, they were not related to plasma concentrations, and did not differ between treatments.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 21 (1982), S. 433-441 
    ISSN: 1432-1041
    Keywords: antipyrine ; antipyrine metabolites ; drug metabolism ; route of administration ; healthy volunteers ; urinary excretion ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of antipyrine in plasma and saliva, and urinary excretion of its major metabolites, were studied following i.v. and oral administration of antipyrine 500 mg to 6 healthy volunteers. Data from both plasma and saliva showed that the oral bioavailability of antipyrine given as an aqueous solution was complete. The saliva/plasma concentration ratio was constant with time from about 3 h onwards, with a mean value of 0.87 after oral and 0.91 after i.v. administration. It is concluded that the pharmacokinetic parameters of antipyrine can be satisfactorily established on the basis of salivary data, although the volume of distribution and clearance values are then slightly too high. After i.v. administration, 3.8±1.9% of the dose was excreted in urine as unchanged antipyrine in 48h, 24.9±6.3% as 4-hydroxyantipyrine, 16.5±3.2% as norantipyrine, 13.0±2.2% as 3-hydroxymethyl-antipyrine and 5.8±1.0% as 3-carboxy-antipyrine. No significant differences were observed following oral administration. The half-lives calculated from the linear part of the urinary excretion rate curves of the metabolites were about the same for oral and i.v. administration, and were of the same order of magnitude as the elimination half-life of parent drug in plasma and saliva. It is important for determination of the ultimate metabolite ratio that urine is collected for at least 36h, because there is a delay in the excretion of 3-hydroxymethyl-antipyrine in urine.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of pharmacokinetics and pharmacodynamics 3 (1975), S. 1-11 
    ISSN: 1573-8744
    Keywords: hexobarbital pharmacokinetics ; intravenous infusion ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The plasma levels of hexobarbital in humans were determined during and after a 30-min or 60-min zero-order intravenous infusion. Hexobarbital kinetics could be described by conceiving the body to exhibit two compartments. The plasma concentrations were fitted to the postinfusion equation and the parameters intrinsic to the two- compartment open model were estimated. The elimination half-life varied considerably among the 14 individuals (160–441 min), which could mainly be explained by the greatly varying metabolic clearance of the compound (123–360 ml /min). The apparent volume of distribution per kilogram of body weight was relatively constant (1.10±0.12 liters/kg).
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  • 8
    ISSN: 1436-6215
    Keywords: Strontium ; oraler Strontium-Test ; Calcium ; Absorption ; gesunde Probanden ; Strontium ; oral strontium test ; calcium ; absorption ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary Intestinal strontium absorption has been discussed recently as an indirect measure for calcium uptake. Prerequisite for the clinical use of an oral strontium test is the availability of a reliable procedure including controlled strontium supply, sample pretreatment and analysis as well as the assessment of normal values. In the present study, a group of young females (n=33; 24.0 ± 2.7 y; BMI 21.5 ± 1.9) received an oral dose of 2.27 mmol strontium in a standardized breakfast that contained 0.625 mmol calcium. Before and 220 min after the bolus serum strontium concentrations were determined by means of atomic absorption spectrophotometry (coefficient of variation: within day 4.8 %, n=10; day-to-day 9.5 %, n=8). The error of the method was 2.7 %. Calculation of the fractional strontium absorption rate considered the respective distribution volume (extracellular fluid; either estimated using body weight or determined by means of bioimpedance analysis [BIA]). Average absorption rates were 13.3 ± 3.1 % and, considering BIA measurement 13.6 ± 2.6 %, respectively. Smoking, exercise and, use of oral contraceptives showed no effects. Our oral strontium test is characterized by excellent reliability, easy handling and low costs and, thus, is suitable for routine use.
    Notes: Zusammenfassung Die Erfassung der Strontiumabsorption wird heute als indirektes Verfahren zur Beurteilung der intestinalen Calciumabsorption diskutiert. Voraussetzung für die klinische Anwendung ist ein vertrauenswürdiges Testverfahren inclusive kontrollierter Strontiumgabe, Probenaufarbeitung und -analyse sowie die Erfassung von Normalwerten. Für unsere Studien wurde ein Kollektiv junger Frauen (n=33, 24,0 ± 2,7 Jahre; BMI 21,5 ± 1,9) herangezogen. Die Probandinnen erhielten eine Bolusgabe von 2,27 mmol Strontium zusammen mit einem Standardfrühstück (ca. 0,625 mmol Calcium). Vor und 220 min nach der Bolusgabe erfolgte die Bestimmung des Serum-Strontiumgehaltes mittels Atomabsorptionsspektrometrie. Der Variationskoeffizient der Methode lag innerhalb eines Tages bei 4,8 % (n=10) und von Tag zu Tag 9,5 % (n=8). Der Fehler der Methode betrug 2,7 %. Die Berechnung der fraktionellen Strontiumabsorptionsrate erfolgte unter Berücksichtigung des entsprechenden Verteilungsraumes (Extrazellulärflüssigkeit; Schätzverfahren über Körpergewicht bzw. Bioimpedanz-Analyse [BIA]). Die Strontiumabsorptionsrate lag im Mittel bei 13,3 ± 3,1 %, unter Berücksichtigung der BIA-Werte bei 13,6 ± 2,6 %. Rauchen, sportliche Aktivität bzw. Einnahme oraler Kontrazeptiva zeigten keinen Einfluß. Das hier vorgestellte Testverfahren ist aufgrund seiner hohen Vertrauenswürdigkeit und relativ einfacher Handhabung für Routine-untersuchungen geeignet.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 631-634 
    ISSN: 1432-1041
    Keywords: salbutamol ; albuterol ; pharmacokinetics ; bioavailability ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Salbutamol was administered to sixteen healthy male volunteers intravenously and by mouth in liquid, tablet, and capsule form using a Latin-Squares design. Pharmacokinetic parameters from intravenous data were similar to previously reported values obtained with oral administration, with a mean terminal half-life of 3.8 h and a mean clearance of 439 ml·min−1·1.73 m−2. Peak plasma concentrations of 10–20 ng·ml−1 were obtained 1–3 h following oral administration. The absolute bioavailability of each of the oral preparations was 44%. While statistically significant differences in lag time and time to peak concentration were noted among the various oral preparations, the drug is rapidly absorbed in all three dosage forms and the observed differences are unlikely to be of clinical significance.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 39 (1990), S. 395-397 
    ISSN: 1432-1041
    Keywords: atropine ; exercise ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven healthy males (19–32 y) underwent each of four separate conditions in a repeated measures design. Five of these subjects underwent an additional trial. In four of five trials subjects received 2.0 mg atropine sulfate intramuscularly in the anterolateral portion of the left thigh: at rest (T1); following completion of a single exercise (Ex) bout (T2), (Each bout consisted of 25 min of stationary cycling at 40% VO2 max with 5 min of seated rest), prior to three Ex bouts (T3) and following one and prior to three Ex bouts (T5). Trial 4 (T4) was the same as T3 with the substitution of a saline placebo. Serum samples were collected over a 12 h period and atropine concentration was determined by RIA. Ex trials were compared to T1. Ex prior to atropine (T2) significantly decreased the mean volume of distribution (Vz, 278 vs 2321). Ex in T3 significantly decreased the serum half life (t1/2, 4.2 vs 3.5 h), Vz (278 vs 1981), and clearance (CL, 763 vs 638 ml·min−1) and significantly increased the peak concentration (Cp, 6.7 vs 12.3 ng·ml−1) and area under the curve (AUC, 44.1 vs 53.1 ng·ml−1). In T5, Ex significantly decreased the t1/2 (3.4 h), Vz (182 l) and CL (575 ml·min−1) and significantly increased the absorption rate constant (ka, 0.482 vs 1.1 min−1), elimination rate constant (ke, 0.0012 vs 0.0015 min−1), Cp (14 ng·ml−1) and AUC (53.3 ng·h·ml−1). These results demonstrate that moderate Ex either prior to and/or immediately following drug administration has the capacity to significantly modify atropine pharmacokinetics.
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