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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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  • 2
    Electronic Resource
    Electronic Resource
    Determination of β-methyldigoxin and its metabolites by high-performance liquid chromatography and fluorescence polarization immunoassay
    Amsterdam : Elsevier
    Journal of Chromatography B: Biomedical Sciences and Applications 489 (1989), S. 425-431 
    Details
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/S0378-4347(00)82925-4
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  • 3
    Electronic Resource
    Electronic Resource
    Seasonal variation in serum total concentrations of cholesterol and protein in elderly subjects
    Amsterdam : Elsevier
    Clinica Chimica Acta 212 (1992), S. 85-87 
    Details
    ISSN: 0009-8981
    Keywords: Elderly subject ; Seasonal variation ; Total cholesterol ; Total protein
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0009-8981(92)90141-C
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  • 4
    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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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and pharmacodynamics of propranolol stereoisomers in hyperthyroid patients (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 197-203 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; hyperthyroidism ; stereoisomers ; radioimmunoassay ; beta-receptor sensitivity ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of propranolol stereoisomers after administration of a single oral dose of the racemic drug was investigated in seven hyperthyroid patients before and after antithyroid drug therapy. The possibility of hypersensitivity to propranolol in the patients was evaluated by constructing plasma propranolol concentration — beta-blocking effect curves. There was no statistically significant difference in elimination half-life (t1/2) between (±)- and (−)-propranolol before and after antithyroid drug therapy. However, the plasma clearance ( $$\dot V_p $$ ) of (−)-propranolol was smaller than that of (±)-propranolol, and the difference was statistically significant after antithyroid drug therapy. Decreased $$\dot V_p $$ was observed in 3 aged hyperthyroid patients compared to the value after antithyroid drug therapy. $$\dot V_p $$ decreased or did not change in young patients after therapy. No significant difference was observed in the relationship between the tilt-induced pulse rate response and plasma propranolol concentration when treated patients became euthyroid compared to their response in the hyperthyroid state.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561949
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  • 6
    Electronic Resource
    Electronic Resource
    Clinical pharmacology of a new β-adrenoceptor blocking drug, befunolol (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 189-195 
    Details
    ISSN: 1432-1041
    Keywords: befunolol ; propranolol ; pharmacokinetics ; pharmacodynamic effects ; beta-adrenoceptor blocking agent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Repeated doses of a new β-adrenoceptor blocking agent, befunolol, were administered orally to adult male volunteers for a cross-over comparison with propranolol. The β-adrenoceptor blocking activity of befunolol was greater than that of propranolol when assessed by the percentage reduction in exercise-induced tachycardia. The elimination half-life of drug was significantly prolonged on repeated administration of propranolol, but not of befunolol. The percentage reduction in exercise-induced tachycardia was highly correlated with the log plasma level of each drug. Both drugs produced a significant reduction in pre-exercise systolic and diastolic blood pressure, and significant attenuation of exercise-induced rise in systolic blood pressure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547552
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  • 7
    Electronic Resource
    Electronic Resource
    Time-dependent change in the effect of probucol in subjects with elevated cholesterol (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 299-301 
    Details
    ISSN: 1432-1041
    Keywords: Probucol ; elevated cholesterol, chronopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A time-dependent change in the cholesterol-lowering effect of probucol has been evaluated in 20 subjects with elevated cholesterol. Probucol 500 mg was given once daily at 07.00 h (day trial) or 19.00 h (night trial) for 3 months according to a crossover design. Fasting blood samples were obtained during the control period and at the end of each treatment period. Serum concentrations of total and HDL-cholesterol were significantly decreased by both the treatments with probucol [total cholesterol (mmol · l−1): control 6.58; day trial 5.41; night trial 5.10; HDL-cholesterol (mmol · l−1): control 1.35; day trial 1.06; night trial 0.96]. These parameters were significantly lower in the night trial than in the day trial. The data indicate that the cholesterol-lowering effect of probucol varies with its time of administration in subjects with elevated cholesterol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02333027
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  • 8
    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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  • 9
    Electronic Resource
    Electronic Resource
    Effect of treatment at night with S-1452, a thromboxane A2 receptor antagonist, on the morning rise in platelet aggregation (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 501-505 
    Details
    ISSN: 1432-1041
    Keywords: S-1452 ; thromboxane A2 receptor antagonist ; nocturnal dosage ; platelet aggregation ; circadian rhythm ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary It is well known that platelet aggregation shows a morning rise, which may contribute to the increase in the onset of ischaemic heart diseases during the morning period. The present study was undertaken to determine whether nocturnal dosage with S-1452, a thromboxane AZ receptor antagonist, would blunt the morning rise in platelet aggregability. S-1452 50 mg or placebo were given orally to 8 healthy subjects at 10.00 h (day trial) or 22.00 h (night trial) according to a cross-over design. Plasma concentrations of S-1452 and its metabolites, bisnor-( + )-S-145 and tetranor-(+ )-S-145, and platelet aggregation were determined during the 12-hour period following the dose. Mean plasma concentrations of S-1452, bisnor-( + )-S-145 and tetranor-(+ )-S-145 during the absorption phase were lower after the nocturnal dose than after the morning dose. The maximum plasma concentration and area under the plasma concentration-time curve of the compounds were also lower and the time to the maximum concentration were delayed after the treatment at night. A morning rise in platelet aggregation was observed following placebo treatment. The inhibitory effect of S-1452 on platelet aggregation was observed at 3 hours and persisted for up to 9 h in both trials. The results suggest that S-1452 is absorbed more slowly after the nocturnal dose than after the morning dose. However nocturnal treatment with 50 mg S-1452 may blunt the morning rise in platelet aggregability.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02285091
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  • 10
    Electronic Resource
    Electronic Resource
    The effect of age on diurnal variation in the pharmacokinetics of propranolol in hypertensive subjects (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 489-492 
    Details
    ISSN: 1432-1041
    Keywords: Chronopharmacology ; Propranolol ; absorption ; age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary There is diurnal variation in the absorption rate of propranolol in younger subjects. This study was undertaken to examine the effect of age on the chronopharmacokinetics of propranolol. We gave 20 mg of propranolol orally to 13 younger and 11 older hypertensive subjects at 09.00 h (day study) or 21.00 h (night study) in a cross-over design. Plasma concentrations of propranolol and its metabolites, 4-hydroxypropranolol and naphthoxylactic acid, were determined just before and at 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 h after dosage. In the younger subjects the absorption rate constant (ka) of propranolol and its maximum plasma concentration (Cmax) were significantly higher and the time to maximum concentration (tmax) was significantly shorter in the day than at night. There were similar time-variant changes in Cmax and tmax for 4-hydroxypropranolol and naphthoxylactic acid. In contrast, there were no time-variant changes in ka, Cmax and tmax of propranolol and its metabolites in the older subjects. These results suggest that propranolol is absorbed more rapidly after morning dosing than after night-time dosing in younger but not in older subjects. Based on these findings, we speculate that the time-variance in the absorption rate or first-pass elimination, or both, of propranolol diminish with age.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315550
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