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  • Articles  (22)
  • pharmacodynamics  (22)
  • Springer  (22)
  • American Chemical Society
  • Annual Reviews
  • Cambridge University Press
  • Elsevier
  • 2020-2024
  • 1985-1989  (12)
  • 1980-1984  (10)
  • Chemistry and Pharmacology  (22)
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  • Articles  (22)
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  • Springer  (22)
  • American Chemical Society
  • Annual Reviews
  • Cambridge University Press
  • Elsevier
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  • Chemistry and Pharmacology  (22)
  • Medicine  (18)
  • 1
    Electronic Resource
    Electronic Resource
    Lack of effect of astemizole on ethanol dynamics or kinetics (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 567-568 
    Details
    ISSN: 1432-1041
    Keywords: astemizole ; ethanol ; antihistamine ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of astemizole (10 mg daily for 7 days) on the kinetics and CNS depressant activity of ethanol have been examined in a double-blind cross-over study agonist placebo in 7 volunteers. There was no significant change in the elimination rate or AUC of the plasma ethanol concentration-time curve after astemizole. Central nervous system effects of ethanol as monitored by visual analogues of sedation, visual discrimination, pursuit rotor and reaction time were also unaffected by astemizole pretreatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542130
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetic and pharmacodynamic study of the combination of furosemide retard and triamterene (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 191-195 
    Details
    ISSN: 1432-1041
    Keywords: furosemide ; triamterene ; drug combination ; pharmacodynamics ; pharmacokinetics ; furosemide retard ; triamterene metabolite ; urine potassium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacodynamics and pharmacokinetics of the combination of furosemide retard (30 mg)/triamterene (50 mg) were compared with furosemide (30 mg) in 18 healthy male volunteers aged 39.3±6.3 years. After the administration of furosemide the onset of its effect was very rapid, reaching a maximum between 1.5 to 3 h, and followed by rebound after 9 to 10.5 h. In contrast the combination furosemide retard/triamterene showed a protracted course with a duration of effect up to 12 h. The general effect over 12 h of the two preparations was equivalent with respect to the excretion of urine, sodium, chloride and calcium, but the combination caused significantly less excretion of potassium (p≤0.05) than furosemide. After a lag-phase of 33.9±5.4 min the maximum plasma concentration of furosemide was reached after 3.47±0.66 h, and the elimination half-life was approximately 2 h. After a lag-phase of 33.0±17.8 min the maximum plasma concentration of the main metabolite of triamterene, the OH-TA sulphuric acid ester, was reached after 1.7±0.59 h, and its elimination half-life amounted to 1.25±0.37 h. Because of the sustained release of furosemide from the retard-formulation, its principal pharmacokinetic parameters were better adapted to those of triamterene. The consequences were not only a protracted effect but also an improved electrolyte profile, especially with regard to reduced loss of potassium. In the case of renal insufficiency, however, the potassium level in serum might be increased to an undesirable extent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00630285
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  • 3
    Electronic Resource
    Electronic Resource
    The pharmacodynamic and pharmacokinetic interaction of flecainide acetate with propranolol: Effects on cardiac function and drug clearance (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 97-99 
    Details
    ISSN: 1432-1041
    Keywords: flecainide ; propranolol ; pharmacodynamics ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610389
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  • 4
    Electronic Resource
    Electronic Resource
    Penbutolol: Pharmacokinetics, effect on exercise tachycardia, and in vitro inhibition of radioligand binding (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 613-623 
    Details
    ISSN: 1432-1041
    Keywords: penbutolol ; beta-adrenoceptor blockade ; pharmacokinetics ; pharmacodynamics ; in vitro/in vivo correlation ; radioreceptor assay ; active metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of penbutolol 40 mg, its reduction in exercise-induced tachycardia, and the in vitro inhibition of radioligand binding to beta-adrenoceptors by plasma have been investigated in 7 healthy volunteers. The peak penbutolol concentration of 285 ng/ml was observed 1.2 h after administration, and the maximum of 4′-OH-penbutolol of 4.76 ng/ml was found after 1.64 h. Penbutolol was detected for up to 48 h, and 4′-OH-penbutolol dropped below the limit of detection after about 10 h. The terminal plasma concentration of penbutolol declined with an average half-life of 19 h. The maximum reduction in exercise-induced tachycardia was 33 beats/min 2.6 h after taking penbutolol. There was still a significant reduction of about 7 beats/min after 48 h. This effect could be adequately explained by the concentration-time course of penbutolol in combination with Clark's model of the concentration-effect relationship. Antagonist activity in plasma caused 91% inhibition of radioligand binding in vitro to beta2-adrenoceptors on rat reticulocyte membranes 1.6 h after intake of penbutolol. By 48 h after intake, radioligand binding was still significantly inhibited (23%). The in vitro inhibition of radioligand binding by plasma showed a linear correlation with the reduction in exercise-induced tachycardia for all phases of the workload. The time course of the reduction in heart rate was completely explained by the in vitro inhibition of radioligand binding. However, it was not possible to explain the in vitro inhibition of radioligand binding by the concentration-time course of penbutolol using a simple competition model, although both variables were based on the same sampling site. When the in vitro inhibition of radioligand binding was plotted against the penbutolol concentration at the same sampling times (with both variables transformed to multiples of the apparent inhibition constant) the discrepancy became even more apparent as time-related counterclockwise hysteresis. None of the known metabolites of penbutolol can explain the discrepancy between the penbutolol concentration and the inhibition of radioligand binding in vitro. It appears that an other active metabolite is formed, which contributes to the effect in vitro and in vivo and so can explain the observed discrepancy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637597
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  • 5
    Electronic Resource
    Electronic Resource
    Alteration by burn injury of the pharmacokinetics and pharmacodynamics of cimetidine in children (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 361-367 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; burned children ; stress ulceration ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the mechanisms of the increased dosage requirements of the H2-receptor antagonist cimetidine in paediatric burned patients in a pharmacokinetic and pharmacodynamic study. Cimetidine (10–15 mg·kg−1) was given to 21 burned children and multiple blood samples were obtained for determination of plasma cimetidine concentrations and pharmacokinetic analysis. The relation of gastric pH to plasma cimetidine concentrations was studied in five of these children who had nasogastric tubes. In an additional four patients the effects of cimetidine on gastric pH were studied during a continuous infusion of cimetidine, which maintained steady-state plasma cimetidine concentrations above 0.5 µg·ml−1. The mean (SEM) clearance of cimetidine in burned children was 16.22 ml·kg−1 and cimetidine half-life was 1.06 h. The cimetidine clearance and half-life values were significantly higher in burned children compared with our previously reported values for normal adult patients, 8.2 ml·min·kg−1 and 2.21 h respectively. Endogenous creatinine clearance normalized to 70 kg in burned children was 190 ml·min−1. In burned children 41% of the dose of intact cimetidine was excreted during 8 h of the study compared with 45% excretion during 24 h in healthy adult controls previously reported. The correlation coefficient between creatinine and cimetidine clearances was 0.93 (r 2=0.85). The plasma concentration of cimetidine needed to increase gastric pH to ≥4.0 was ≥1.0 µg·ml−1, which contrasts with the value of 〉0.5 µg·ml−1 required for adult burned patients. These findings support the hypothesis that the higher dosage requirements of cimetidine in burned children is due both to enhanced elimination kinetics and to alterations in target organ sensitivity, requiring higher than normal plasma concentrations for the desired effect. In burned children Cimetidine should be given in higher doses and/or more frequently.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558296
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  • 6
    Electronic Resource
    Electronic Resource
    Propranolol pharmacokinetics and pharmacodynamics after single doses and at steady-state (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 315-318 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; pharmacodynamics ; pharmacokinetics ; beta-blockade ; sustained-release propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The duration and extent of cardiac beta-blockade and their relationship to propranolol pharmacokinetics were assessed in nine healthy volunteers. Each subject received 160 mg of regular propranolol (R), 160 mg of sustained-release propranolol (SR) and no drug (control), both as single doses and once daily for 7 days. After single doses and at steady-state, both products caused a decrease in exercise heart rate for at least 24 h, compared to control. The time course of effect was similar to the time course of serum propranolol concentration. The oral clearance of propranolol decreased from single doses to steady-state for both R and SR; however, the difference achieved statistical significance only for R. These changes were reflected in mean accumulation ratios (AUC steady-state 0–24 h/AUC single dose 0-infinity) of 1.49 and 1.68 for R and SR, respectively. The pharmacokinetic data are consistent with a decrease in intrinsic hepatic clearance of propranolol, leading to an increase in bioavailability at steady-state. Despite a two-fold difference in the bioavailability of R and SR, there was no difference in the area under the effect-time curve at steady-state.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637569
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacologic evaluation of loratadine (SCH 29851), chlorpheniramine and placebo (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 247-250 
    Details
    ISSN: 1432-1041
    Keywords: loratadine ; chlorpheniramine ; placebo ; histamine ; pharmacodynamics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihistaminic effect of loratadine (160 mg) was compared in twenty-four normal male volunteers to chlorpheniramine maleate (4 mg) and placebo in a double blinded 3-way cross-over study of latin square design. After receiving single oral doses of each medication, the wheal response to serial 0.1 ml intradermal histamine (2 µg) and saline (control) injections were recorded over a 24-h period. The calculated wheal areas were compared to baseline measurements. The results were analyzed by analysis of variance. Loratadine exhibited a more pronounced inhibition of histamine wheal formation than placebo or chlorpheniramine maleate (p〈0.003). In contrast to chlorpheniramine maleate which had a duration of action of only 3 h, loratadine inhibited the response for the entire observation period between 1 and 24 h post-dose. Although sedation was observed less frequently with loratadine (Placebo,n=2; chlorpheniramine,n=3; and loratadine,n=1), the relative incidence were not statistically significant.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606669
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  • 8
    Electronic Resource
    Electronic Resource
    Clinical pharmacology of etintidine in patients with duodenal ulcer (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 495-500 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; etintidine ; duodenal ulcer ; histamine H2 antagonist ; gastric acidity ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The gastric antisecretory activity of etintidine, a new histamine H2-receptor antagonist, was evaluated in 5 patients with quiescent duodenal ulcer disease. Meal-stimulated acid secretion was measured after 100 and 300 mg oral doses of etintidine, 100 and 300 mg oral doses of cimetidine, and placebo. Reductions from placebo in four-hour gastric acid secretion were 49, 65, 80, and 94%, with 100 mg cimetidine, 100 mg etintidine, 300 mg cimetidine, and 300 mg etintidine, respectively. Drug concentrations in plasma were determined by HPLC. The pharmacokinetics of the 2 drugs were similar. We analyzed sigmoid-shaped concentration-response curves to both agents; the concentrations causing 50% inhibition of meal-stimulated gastric acid secretion were 0.44±0.04 and 0.15±0.04 µg/ml for cimetidine and etintidine, respectively. However, characteristics of these curves were such that the potency difference diminished at higher concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637495
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  • 9
    Electronic Resource
    Electronic Resource
    Relationships between several pharmacokinetic parameters and psychometric indices of subjective effects of Δ9-tetrahydrocannabinol in man (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 633-637 
    Details
    ISSN: 1432-1041
    Keywords: delta-9-tetrahydrocannabinol ; mood ratings ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This study explored the relationships in man between various pharmacological effect of Δ9-tetrahydrocannabinol (THC), plasma THC concentration, and pharmacokinetic parameters of THC. Three male and three female experienced marihuana users smoked two standard marihuana cigarettes. The relationships between heart rate, subjective “high” rating, Linear Mood Scale factors, and plasma THC concentration were assessed. Significant correlations were observed between various Linear Mood Scale factors and pharmacokinetic parameters reflecting the magnitude of drug intake and the degree of temporal dissociation between the time courses of plasma THC concentration and pharmacological effects (tachycardiac effect, “high”). In particular, the disturbed/weird and sensitive/aware mood factors correlated positively with pharmacokinetic measures of drug intake and time lag to effect. A more reliable index of intoxication with THC may be provided by the global subjective “high” rating, rather than other ratings more specific for particular moods.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542351
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  • 10
    Electronic Resource
    Electronic Resource
    Disposition of intravenous diazepam in young men and women (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 207-213 
    Details
    ISSN: 1432-1041
    Keywords: diazepam ; benzodiazepines ; N-desmethyldiazepam ; plasma ; saliva ; pharmacokinetics ; pharmacodynamics ; psychomotor ; impairment ; oral contraceptives
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of a single intravenous dose of diazepam (10 mg) was studied in 11 young, healthy subjects (6 males and 5 females on oral contraceptives). Plasma samples were obtained over 28 days and diazepam and N-desmethyldiazepam plasma concentrations and diazepam free fractions were determined. The salivary excretion of diazepam and N-desmethyldiazepam was studied over 72 h. A series of psychomotor performance tests were administered over the first 8 h. Interindividual variation in mean diazepam disposition over time is not principally related to variation in plasma protein binding; 93% of the variation in clearance is accounted for by variation in intrinsic clearance. Interindividual variation in diazepam disposition is modest but the plasma clearance of diazepam in women on oral contraceptives (median 14.0 ml/min) is significantly (p=0.004) less than in men (median 23.4 ml/min) and the area under the curve (AUC) of diazepam is highly correlated with the AUC of the principal active metabolite (r=0.90, p〈0.001). The AUC of N-desmethyldiazepam (median 9.2 µg·h/ml) in women is greater (p=0.06) than in men (median 7.5 µg·h/ml). On chronic administration of diazepam, therefore, women taking oral contraceptives will have greater plasma concentrations per unit dose of both diazepam and N-desmethyldiazepam than men. The clearance of diazepam in control groups of 11 young men (median 23.8 ml/min) and 10 young women not taking oral contraceptives (median 26.8 ml/min) is not significantly different. Plasma and salivary concentratrions of diazepam are correlated (p〈0.001) but the predictive value of this correlation is limited (r=0.70) since the ratio of salivary to plasma concentrations varies significantly over the day. The use of calculated free diazepam plasma concentrations does not improve the correlation (r=0.68) but the slope of this regression (1.00) is that predicted by theory.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544599
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