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  • 1
    Electronic Resource
    Electronic Resource
    Clinical pharmacology and clinical trials in Japan (1996)
    Springer
    Journal of molecular medicine 74 (1996), S. 479-486 
    Details
    ISSN: 1432-1440
    Keywords: Clinical pharmacology ; Clinical trials ; Drug development ; Drug therapeutics ; Informed consent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clinical pharmacology is the pursuit of rational therapeutics by following the scientific principles of medicine and pharmacology. In Japan the roles for clinical pharmacology and clinical pharmacologists have been evolving since the discipline appeared in the 1950s. Clinical pharmacology and clinical trials for drug development depend on each other, and clinical pharmacologists play an important role in drug development in Japan. As the discipline becomes more important and complicated, many issues regarding drug therapeutics and clinical trials in Japan have been raised, and several points of view have been expressed. The following suggestions have been made to improve clinical pharmacology in Japan: (a) Medical education in the field of clinical pharmacology must be improved by creating or improving clinical pharmacology programs in medical schools. (b) The appropriate infrastructure for clinical trials must be established so that the physicians' workload is reduced, and patients' participation in clinical trials becomes much easier. (c) Scientific and ethical standards of the pharmaceutical industry must be improved, and the effort should be made to produce drugs with new mechanisms of action or with significant expected benefits. (d) The regulatory agency must provide stronger support, encompassing all the various points of view of academic institutes and the pharmaceutical industry. In light of the enthusiasm demonstrated by the government, physicians, and pharmaceutical industry in Japan for continued progress in clinical pharmacology, it seems likely that all its challenges will be overcome in the near future. Hence, despite the various problems discussed here the future seems promising for the continued development of clinical pharmacology.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00217525
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    The effect of propranolol on urinary prostaglandin E2 after frusemide administration in healthy subjects (1987)
    Springer
    European journal of clinical pharmacology 31 (1987), S. 605-607 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; prostaglandin E2 ; frusemide ; plasma renin activity ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have evaluated the effect of propranolol on urinary prostaglandin E2 (PGE2) excretion after frusemide administration in 8 healthy subjects. Urine was collected for 60 min after frusemide administration (20 mg intravenously) with or without propranolol pretreatment, and urinary excretion of PGE2, frusemide, and sodium were determined. Plasma renin activity (PRA) was also measured before and 60 min after frusemide administration. Urinary PGE2 excretion after frusemide administration and frusemide-stimulated PRA were reduced after propranolol pretreatment. However, urine volume and the urinary excretion of frusemide and sodium were not influenced by propranolol pretreatment. These results suggest that urinary PGE2 excretion after frusemide administration may be reduced by propranolol and that the mechanism responsible for the effect of proranolol on the frusemide-induced renal PGE2 production may be, at least in part, secondary to inhibition of the renin-angiotensin system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606639
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Effect of α1-adrenoceptor antagonists, prazosin and urapidil, on a finger skin vasoconstrictor response to cold stimulation (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 371-375 
    Details
    ISSN: 1432-1041
    Keywords: Key words Prazosin ; Urapidil; Vasoconstrictor response ; laser Doppler flow ; finger tip blood flow ; cold stimulation ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: Cold stimulation causes a finger skin vasoconstrictor response, which is regulated by stimulation of α-adrenergic receptors and is reduced by administration of prazosin. The purpose of this study was to investigate, using a laser Doppler flowmeter, whether the decrease in the finger skin vasoconstrictor response to cold stimulation produced by administration of two different α1-adrenoceptor antagonists, prazosin and urapidil, was correlated with the corresponding plasma drug concentration, and whether this method could be used to evaluate the relative potency of these α1-adrenoceptor antagonists in human subjects. Method: In thirteen healthy male subjects (20–42 y), finger tip skin blood flow was measured during cold stimulation before and 1, 2, 3, 6, and 9 h after administration of placebo, prazosin (1 mg) or urapidil (60 mg). Results: Both prazosin and urapidil significantly decreased the vasoconstrictor response to cold stimulation. The degree of the decrement in the response indicated by the reduction ratio was significantly correlated with the plasma concentration of prazosin and urapidil. The α1-adrenoceptor blocking activity of prazosin estimated by the regression lines was about 130-times more potent than that of urapidil. Conclusion: These findings suggest that the cold stimulation response of finger skin vasoconstriction may be used to evaluate the relative α1-adrenoceptor blocking potency of drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050034
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of α1-adrenoceptor antagonists, prazosin and urapidil, on a finger skin vasoconstrictor response to cold stimulation (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 371-375 
    Details
    ISSN: 1432-1041
    Keywords: Prazosin ; Urapidil ; Vasoconstrictor response ; laser Doppler flow ; finger tip blood flow ; cold stimulation ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: Cold stimulation causes a finger skin vasoconstrictor response, which is regulated by stimulation of α-adrenergic receptors and is reduced by administration of prazosin. The purpose of this study was to investigate, using a laser Doppler flowmeter, whether the decrease in the finger skin vasoconstrictor response to cold stimulation produced by administration of two different α1-adrenoceptor antagonists, prazosin and urapidil, was correlated with the corresponding plasma drug concentration, and whether this method could be used to evaluate the relative potency of these α1-adrenoceptor antagonists in human subjects. Method: In thirteen healthy male subjects (20–42 y), finger tip skin blood flow was measured during cold stimulation before and 1, 2, 3, 6, and 9 h after administration of placebo, prazosin (1 mg) or urapidil (60 mg). Results: Both prazosin and urapidil significantly decreased the vasoconstrictor response to cold stimulation. The degree of the decrement in the response indicated by the reduction ratio was significantly correlated with the plasma concentration of prazosin and urapidil. The α1-adrenoceptor blocking activity of prazosin estimated by the regression lines was about 130-times more potent than that of urapidil. Conclusion: These findings suggest that the cold stimulation response of finger skin vasoconstriction may be used to evaluate the relative α1-adrenoceptor blocking potency of drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00203780
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    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Effect of diltiazem on the pharmacokinetics of propranolol, metoprolol and atenolol (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 67-70 
    Details
    ISSN: 1432-1041
    Keywords: diltiazem ; propranolol ; metoprolol ; atenolol ; pharmacokinetics ; drug interaction ; beta-adrenoceptor blockade ; healthy volunteers ; pharmacodynamic effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic interaction between diltiazem and three β-adrenoceptor blockers propranolol, metoprolol and atenolol was investigated in healthy volunteers given diltiazem 30 mg or placebo t.d.s. for 3 days, followed by a single dose of propranolol 20 mg, metoprolol 40 mg or atenolol 50 mg. The AUCs of propranolol and metoprolol were significantly increased after diltiazem and it significantly prolonged the elimination half-life of metoprolol. In contrast, it did not significantly affect the pharmacokinetics of atenolol. Propranolol significantly decreased the resting pulse rate after diltiazem pretreatment as compared to placebo. The results indicate that diltiazem impaired the clearance of propranolol and metoprolol, which are principally metabolized by an oxidative pathway, and that the kinetic interaction between diltiazem and propranolol may partly be related to the significant reduction in the pulse rate produced by the latter.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561026
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    Paper (German National Licenses)
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  • 6
    Electronic Resource
    Electronic Resource
    Clinical pharmacology and clinical trials in Japan (1996)
    Springer
    Journal of molecular medicine 74 (1996), S. 479-486 
    Details
    ISSN: 1432-1440
    Keywords: Key words Clinical pharmacology ; Clinical trials ; Drug development ; Drug therapeutics ; Informed consent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Clinical pharmacology is the pursuit of rational therapeutics by following the scientific principles of medicine and pharmacology. In Japan the roles for clinical pharmacology and clinical pharmacologists have been evolving since the discipline appeared in the 1950s. Clinical pharmacology and clinical trials for drug development depend on each other, and clinical pharmacologists play an important role in drug development in Japan. As the discipline becomes more important and complicated, many issues regarding drug therapeutics and clinical trials in Japan have been raised, and several points of view have been expressed. The following suggestions have been made to improve clinical pharmacology in Japan: (a) Medical education in the field of clinical pharmacology must be improved by creating or improving clinical pharmacology programs in medical schools. (b) The appropriate infrastructure for clinical trials must be established so that the physicians’ workload is reduced, and patients’ participation in clinical trials becomes much easier. (c) Scientific and ethical standards of the pharmaceutical industry must be improved, and the effort should be made to produce drugs with new mechanisms of action or with significant expected benefits. (d) The regulatory agency must provide stronger support, encompassing all the various points of view of academic institutes and the pharmaceutical industry. In light of the enthusiasm demonstrated by the government, physicians, and pharmaceutical industry in Japan for continued progress in clinical pharmacology, it seems likely that all its challenges will be overcome in the near future. Hence, despite the various problems discussed here the future seems promising for the continued development of clinical pharmacology.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001090050050
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    Circadian influence on effect of propranolol on exercise-induced tachycardia in healthy subjects (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 133-137 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; chronopharmacology ; exercise-induced tachycardia ; pharmacokinetics ; healthy volunteers ; gastio-intestinal absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Following a cross-over design propranolol 20 mg p.o. was given to 7 healthy subjects at 09.00 h and 21.00 h at an interval of 1 week. Heart rate (HR) during submaximal ergometer exercise was measured at four intervals during 10 h after treatment. Plasma propranolol concentrations were also determined. The suppressive effect (%R) of propranolol on the rise in HR during exercise after the morning dosage was significantly greater at 1.5 h and tended to be greater 3 h after administration than at comparable times in the evening trial. Mean plasma propranolol concentrations during the early phase were higher after the morning than the evening dose. The maximum plasma concentration (Cmax), area under the plasma concentration-time curve from 0 to 10 h (AUC (0–10)) and absorption rate constant (ka) were significantly greater after the morning dose. The time to maximum concentration (tmax) and elimination half-life (t1/2) of the morning and evening dosages did not differ. A significant correlation was observed between plasma propranolol concentration and %R in HR during exercise in the morning (r=0.74) and evening (r=0.63) trials, and the regression lines of the morning and evening treatments did not differ. The data indicate that the suppressive effect of propranolol on exercise-induced tachycardia was relatively greater after a morning than an evening dose; that propranolol was more rapidly absorbed from the gastrointestinal tract after the morning than the evening dosage; that diurnal changes in the activity of propranolol depend in part on the time of administration and its subsequent effect on plasma concentrations of the drug; and that the antagonist activity of propranolol relative to a given drug concentration may not differ between morning and evening treatments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265971
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    Paper (German National Licenses)
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