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Biomedical subjects

A Fujimura

Publications and source records attributed to A Fujimura.

At least 127 records · Page 7Linked to original sources
PubMed1996

No evidence of a direct venodilatory effect of furosemide in healthy human subjects.

The present study was undertaken to examine whether furosemide, a loop diuretic, has a direct venodilatory effect in healthy male subjects. Furosemide, or amrinone, an inotropic agent with a vasodilatory action, was infused into a dorsal hand vein that had been preconstricted by phenylephrine. The diameter of the vein was measured by a linear variable differential transformer. Venodilation was observed during the infusion of amrinone, but such a response was not detected with furosemide. These findings do not support the hypothesis that furosemide has a direct venodilatory effect in healthy human subjects.

Adult↗
PubMed1996

Influences of bathing and hot weather on the pharmacokinetics of a new transdermal clonidine, M-5041T.

The influences of bathing and hot weather on plasma concentrations of clonidine were examined during application of a new transdermal clonidine system, M-5041T, in eight healthy volunteers. An M-5041T patch containing 6 mg of clonidine was applied on the right chest for 96 hours during winter with or without bathing (40 degrees C for 5 minutes) and also during summer without bathing. Plasma concentrations and urinary excretion of clonidine were determined for a 160-hour period after application. Plasma concentrations of clonidine in the winter trials did not differ significantly with or without bathing. Plasma drug concentration as a whole was significantly higher in the summer trial than in the winter trial, however. The maximum plasma concentration (Cmax), area under the plasma concentration-time curve (AUC), and urinary excretion (Ae) of clonidine also tended to be higher in the summer trial. These results suggest that plasma levels of clonidine are higher after application of M-5041T during hot weather. Although the period of bathing used in this study was short, the influence of bathing seems to be negligible.

Administration, Cutaneous↗
PubMed1996

Clinical pharmacology of multiple-dose losartan, an angiotensin II receptor antagonist, in patients with essential hypertension.

The pharmacokinetic and pharmacodynamic alterations of multiple doses of losartan, an angiotensin II receptor antagonist, were examined in nine patients with essential hypertension. Participants were given placebo once daily for the first 7 days (from day -7 to day -1), and then 50 mg of losartan for the next 9 days (from day 1 to day 9). The 24-hour blood pressure was measured on days -1, 1, and 7 and blood samples for measurement of losartan and its active metabolite, E-3174, were obtained on days 1 and 7. Plasma concentrations of uric acid and plasma clearance were determined before and during treatment with losartan, and at the end of the study. Pharmacokinetic parameters after the seventh dose, including maximum plasma concentration (Cmax) and time to Cmax (tmax) of losartan and E-3174, did not differ significantly from those after the first dose. The blood pressure lowering effect of losartan, however, was significantly greater after the seventh dose than after the first dose. Plasma uric acid decreased and its plasma clearance (ClUA) increased significantly during repeated administration with losartan. These values returned to pretreatment levels after the end of treatment. These results suggest that although the pharmacokinetic profiles of losartan and E-3174 do not change during repeated administration, the blood pressure lowering effect in hypertensive patients is greater after multiple doses than after a single dose.

Adult↗
PubMed1996

Pharmacokinetics of a new thromboxane A2 receptor antagonist, S-1452, and its effect on platelet aggregation in healthy volunteers.

To study the pharmacokinetics of a new thromboxane A2 (TXA2) receptor antagonist, S-1452, eight healthy volunteers were given placebo or S-1452 orally on four occasions in step-wise increasing doses of 10 mg, 25 mg, and 50 mg separated by 2-week intervals. Blood samples for measurement of plasma concentrations of the drug and of its inhibitory effect on platelet aggregation were obtained for 24 hours after administration. Bleeding time after administration was measured. S-1452 was rapidly absorbed, with a peak plasma concentration at 30 minutes after administration. Thereafter, the drug was rapidly eliminated (elimination half-life, 0.4-0.5 hours), and no drug was detected at 6 hours. The inhibitory effect of S-1452 on platelet aggregation, which was stimulated by the TXA2 receptor agonist U-46619, persisted more than 6 hours after drug administration. Bleeding time was slightly prolonged after a single dose of S-1452. These results suggest that although S-1452 is rapidly eliminated in plasma, its inhibitory effects on platelet aggregation persist for a longer period. Careful observations are needed to prevent potential bleeding episodes during repeated treatment with the drug.

Administration, Oral↗
PubMed1996

Comparison of the antagonistic activity of tamsulosin and doxazosin at vascular alpha 1-adrenoceptors in humans.

alpha 1-Adrenoceptor blockers such as prazosin and doxazosin are used to treat hypertension as well as benign prostatic hyperplasia (BPH), whereas the new alpha 1-adrenoceptor blocker tamsulosin is used only for BPH and does not reduce blood pressure at the doses used to relax prostatic smooth muscle. In contrast to prazosin, tamsulosin has a higher affinity for prostatic than vascular alpha 1-adrenoceptors in vitro. The functional correlate of this observation in humans is the subject of this study. The alpha 1-adrenoceptor blockade by oral tamsulosin (0.2 mg), doxazosin (1 mg) or placebo on finger tip vascular and dorsal hand venous alpha 1-adrenoceptors stimulated by cold treatment (immersion in ice water) and the alpha 1-adrenoceptor agonist phenylephrine, was thus studied in a 3-way crossover study in eight, healthy, male adults. Finger tip vasoconstriction after cold stimulation was assessed by laser Doppler flowmetry. A linear variable differential transformer was used to assess the drug effect on phenylephrine-induced venoconstriction. All study parameters were assessed at around 2 and 3.5 h after oral intake of doxazosin and tamsulosin respectively. The drug plasma levels were not significantly different. No significant differences were found for blood pressure or heart rate in the three treatments in supine and erect position. The reduction in finger tip blood flow after cold stimulation was significantly smaller after doxazosin treatment (P < 0.01) than after tamsulosin or placebo, whereas there was no significant difference between tamsulosin and placebo treatments. The infusion rate of phenylephrine producing a half-maximum venoconstriction was significantly larger after doxazosin than after tamsulosin (P < 0.05) or placebo (P < 0.01), whereas there was again no significant difference between tamsulosin and placebo treatments. The data suggest that, at doses producing equal plasma levels after single oral doses in human subjects, the blocking activity at vascular alpha 1-adrenoceptors is lower for tamsulosin than for doxazosin.

Administration, Oral↗
PubMed1996

Effect of alpha 1-adrenoceptor antagonists, prazosin and urapidil, on a finger skin vasoconstrictor response to cold stimulation.

OBJECTIVES: Cold stimulation causes a finger skin vasoconstrictor response, which is regulated by stimulation of alpha-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 alpha 1-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 alpha 1-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 alpha 1-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 alpha 1-adrenoceptor blocking potency of drugs.

Administration, Oral↗
PubMed1996

Influence of age on venodilator effect of isoproterenol and amrinone.

OBJECTIVE: To investigate the influence of age on the venodilator effect of isoproterenol, a beta-adrenoceptor agonist, and amrinone, a selective phosphodiesterase (PDE) III inhibitor, in human subjects. METHODS: In eight young and eight elderly male subjects, the drugs were infused into a dorsal hand vein preconstricted with phenylephrine and its diameter was measured using a linear variable differential transformer. RESULTS: The maximum venodilation (Emax) induced by isoproterenol was significantly smaller and the infusion rate of isoproterenol required to induce 50% of maximum venodilation (ED50) was significantly larger in the elderly than in the young subjects [Emax: 29.8 vs 95.1%, ED50: 97.3 vs 51.6 ng.min-1]. A significant age-related change in Emax or ED50 was not observed for amrinone (Emax: 95.8 vs 100.8%, ED50: 40.1 vs 31.6 micrograms.min-1). CONCLUSION: The data show that the venodilator effect of amrinone is not influenced by age. As amrinone increases cyclic AMP by inhibition of PDE III, it is suggested that the action of cyclic AMP is not altered by age. The decreased effect of isoproterenol might be caused by reduced production of cyclic AMP in elderly subjects.

Adrenergic beta-Agonists↗
PubMed1996

Effect of food intake on pharmacokinetics and effects of a new thromboxane A2 receptor antagonist, S-1452.

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.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Effect of ranitidine on renal clearance of lomefloxacin.

OBJECTIVE: To examine the effect of ranitidine on the renal clearance of lomefloxacin. SETTING: Department of Clinical Pharmacology, Jichi Medical School. METHODS: Lomefloxacin 200 mg and ranitidine 300 mg or its placebo were given orally in a randomised, double-blind, crossover design. Blood and urine samples were obtained during a 24-h period after dosing. RESULTS: The area under the plasma concentration-time curve and the elimination half-life of lomefloxacin were significantly increased following coadministration with ranitidine. These effects were caused by significant decreases in total (7.8%) and renal (22%) clearance of lomefloxacin. In contrast, creatinine clearance and urinary excretion of electrolytes were not influenced by ranitidine. CONCLUSION: As lomefloxacin and ranitidine are excreted in urine by renal tubular secretion, the present results suggest that the renal tubular secretion of lomefloxacin is diminished by ranitidine. As the reduction in lomefloxacin clearance is only marginal, it is probable that the drug interaction observed in this study is not of clinical significance.

Adult↗
PubMed1996

Effect of probenecid and ranitidine on urinary excretion of lomefloxacin in rats.

To examine the renal tubular transport pathways of lomefloxacin, a new quinolone antibiotic, the agent was injected intravenously with or without pretreatment with probenecid, an organic anion, or ranitidine, an organic cation, in rats. Urinary excretion of lomefloxacin significantly decreased in the probenecid-treated animals. However, no significant decrease was observed in this parameter by pretreatment with ranitidine. These results suggest that lomefloxacin is mainly secreted in urine by the organic anion transport system, while the pathway mediated by the organic cation transport system is negligible.

Animals↗
PubMed1996

Long-term effects of doxazosin, an alpha 1-blocker, on serum lipids in hypertensive patients.

Nowadays practical antihypertensive therapy involves not only simple normalization of blood pressure but also a reduction of the risks of cardiovascular disease. In this multicenter open-label study, the long-term effects of doxazosin, an alpha 1-adrenergic receptor blocker, on serum lipids were prospectively investigated in 253 patients with essential hypertension. They were treated with doxazosin for 1 year. The averaged the blood pressure was maintained at levels lower than 150/90 mmHg throughout 1 year, but heart rate did not increase. After 3 months of doxazosin therapy, total and low density lipoprotein-cholesterol levels in serum were significantly reduced by 3.3% and 3.4%, respectively, and these levels were maintained throughout the study period. This effect of doxazosin on serum lipids was especially prominent in patients with hypercholesterolemia. In addition, the lipid profile of these patients was favorably altered even when other antihypertensive drugs or lipid-lowering drugs had already been used or were used concurrently. These results constitute useful information for physicians who treat hypertension with alpha 1-blockers to reduce the overall risk of cardiovascular disease.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1995

Comparison of venodilatory effect of amrinone and theophylline in human subjects.

Amrinone, a positive inotropic agent, is a selective phosphodiesterase III inhibitor and exerts vasodilatory effect on venous vessels. The present study was undertaken to compare the venodilatory effect of amrinone and theophylline, a nonselective phosphodiesterase inhibitor, in eight healthy male subjects. In a randomized crossover design, one of these drugs was infused into the dorsal hand vein preconstricted by phenylephrine and its diameter was measured using a linear variable differential transformer. The value of maximum vasodilation for amrinone (mean +/- standard deviation, 106% +/- 17%) was similar to that for theophylline (mean +/- standard deviation, 108% +/- 14%). However, the infusion rate of amrinone needed to induce 50% of maximum vasodilation was significantly less than that of theophylline (25 +/- 15 micrograms/minute vs. 192 +/- 87 micrograms/minute, respectively; P < 0.01). These findings suggest that the venodilatory activity of amrinone is more potent than that of theophylline in human subjects.

Adrenergic alpha-Agonists↗
PubMed1995

Effect of losartan, an angiotensin II receptor antagonist, on response of cortisol and aldosterone to adrenocorticotrophic hormone.

Many imidazole derivatives are shown to inhibit adrenal steroid biosynthesis. The present study was undertaken to examine an effect of another imidazole derivative, losartan (an angiotensin II receptor antagonist), on responses of cortisol and aldosterone to adrenocorticotrophic hormone (ACTH). Nine patients with essential hypertension were given placebo orally for 7 days and 50 mg of losartan for the next 9 days. Response of serum cortisol and plasma aldosterone to intramuscular ACTH injection were determined before and at the end of the treatment with losartan. Serum cortisol and plasma aldosterone significantly increased after ACTH injection in both periods of treatment (placebo and losartan). The increments in these parameters during treatment with losartan were not significantly different from those during treatment with placebo. These results suggest that the inhibitory effect of losartan on adrenal steroid biosynthesis is negligible.

Adrenocorticotropic Hormone↗
PubMed1995

Chronopharmacology of enalapril in hypertensive patients.

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 enalapril-induced 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 diminished or eliminated by a switch to night-time administration.

Adult↗