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  • 11
    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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  • 12
    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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  • 13
    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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  • 14
    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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  • 15
    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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  • 16
    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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  • 17
    Electronic Resource
    Electronic Resource
    Effect of furosemide on angiotensin II-mediated prostaglandin I2 production in hypertensive subjects (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 113-115 
    Details
    ISSN: 1432-1041
    Keywords: Furosemide ; 6-keto-PGF1α ; hypertension ; angiotensin II ; captopril ; urinary PGs ; PGI2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The role of angiotensin II (AII) in Prostaglandin I2 (PGI2) production following furosemide has been examined in a placebo-controlled, cross-over study. Furosemide 20 mg was injected intravenously in eight hypertensive subjects already treated with oral captopril 25 mg or a matching placebo. Urinary excretion of 6-keto-PGF1α (a metabolite of PGI2) and PGE2, PRA and AII was increased following furosemide without captopril pretreatment. The rises in urinary 6-keto-PGF1α and PGE2, and plasma AII after furosemide were prevented by the captopril pretreatment. Urinary volume, sodium and furosemide were not affected by captopril. The data indicate that the effect of furosemide on PGI2 production, as reflected by the urinary excretion of 6-keto-PGF1α, was mediated by an action of AII.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280042
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  • 18
    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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  • 19
    Electronic Resource
    Electronic Resource
    Progression of osteoporosis in cancellous bone depending on trabecular structure (1994)
    Springer
    Annals of biomedical engineering 22 (1994), S. 532-539 
    Details
    ISSN: 1573-9686
    Keywords: Osteoporosis ; Trabecular structure ; Bone metabolism ; Femoral neck fracture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Progression of osteoporosis is caused by a decline in bone formation activity relative to the resorption activity. In this paper, the authors carried out a theoretical analysis of the progression of osteoporosis to estimate the osteoporotic change in the upper end of the femur. According to this analysis, the progression rate of osteoporosis in cancellous bone depends on the product of remodeling activity,R act, and the trabecular structure parameter,K tr. To confirm that the theoretical results were reasonably comparable to actual osteoporotic change, these two factors were measured in rabbits. From the results, it was concluded that the highest progression rate was shown in bar/barlike trabecular structure (type 3); the next highest rate, was shown in plate/bar-like structure (type 2); and the plate/plate-like structure (type 1) was the most insensible. Furthermore, the bone volume fractions of cancellous bone were measured at the upper end of human femurs with and without osteoporosis. Then the measured value was compared with the theoretical value for each type of trabecular structure. Results showed that the decrease in bone volume fraction predicted by Eq. 7 was well in accord with the actual decrease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02367089
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