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  • 1
    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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  • 2
    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)
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  • 3
    Electronic Resource
    Electronic Resource
    Chronopharmacology of enalapril in hypertensive patients (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 441-445 
    Details
    ISSN: 1432-1041
    Keywords: Chronopharmacology ; Enalapril ; Hypertension ; bradykinin ; cough
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and pharmacodynamics of enalapril, an angiotensin converting enzyme inhibitor, are reported to vary with the time of administration. The present study was undertaken to examine whether the effect of enalapril on plasma bradykinin (BK), substance P and prostaglandin E2 (PGE2), which are likely to be involved in the mechanism of enalaprilinduced cough, might also be affected by its time of administration. Enalapril 5 mg or placebo was given orally at 10:00 h (day trial) or 22:00 h (night trial) to 12 patients with essential hypertension. Serum concentrations of total drug (enalapril + enalaprilat, its active metabolite) during the day and night trials did not differ significantly at any time. However, serum enalaprilat tended to be higher and its maximum concentration greater in the day trial than in the night trial. Blood pressure 24 h after administration of enalapril was reduced at 22:00 h, but not at 10:00 h. Plasma BK tended to increase following enalapril administration at 10:00 h, but not at 22:00 h. Remarkable increases in plasma BK were observed in two patients in the day trial and one of them also complained of cough. However, no such increase in plasma BK or subsequent adverse effect were recorded in the night trial. Plasma substance P and PGE2 did not change significantly following enalapril administration either in the day or night trial. The results suggest that the response of BK to enalapril is affected by the time of administration. In patients who complain of cough during treatment with enalapril during the daytime, this adverse effect might be dminished or eliminated by a switch to night-time administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194332
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of food intake on pharmacokinetics and effects of a new thromboxane A2 receptor antagonist, S-1452 (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 311-314 
    Details
    ISSN: 1432-1041
    Keywords: Key words S-1452 ; Thromboxane A2 receptor antagonist; food ingestion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To examine the effect of food ingestion on the pharmacokinetics of a new thromboxane A2 (TXA2) receptor antagonist, S-1452, and the inhibitory effect on platelet aggregation. Methods: Fifty milligrams of S-1452 was given orally to eight healthy subjects with or without food. Blood samples for determinations of plasma drug concentrations and of its effects on platelet aggregation were taken for a 12-h post-drug period. Results: The maximum plasma concentration of S-1452 was reduced by 47% and the time to maximum concentration was prolonged from 0.5 to 1.9 h after dosing with food. The inhibitory effect of S-1452 on platelet aggregations induced by U-46619, a TXA2 receptor agonist, and collagen persisted up to 9 h after dosing with and without food. The degrees of inhibition in the two trials did not differ significantly at any point. Conclusion: These results suggest that although the absorption of S-1452 is delayed and, consequently, its plasma concentration is decreased after dosing with food, the inhibitory effect on platelet aggregation is not significantly influenced after 50 mg of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050114
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    Paper (German National Licenses)
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  • 5
    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
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    Paper (German National Licenses)
    Fulltext
  • 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: 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
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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