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Biomedical subjects

A Fujimura

Publications and source records attributed to A Fujimura.

At least 145 records · Page 8Linked to original sources
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↗
PubMed1995

Studies on the development of the articular part of the temporal bone with special reference to the postglenoid process.

The development and significance of the postglenoid process on the articular surface of the temporal bone were studied using 217 Indian skulls, which were divided by their level of tooth eruption into 6 developmental stages; preeruption period (Stage I), initial stage (m1 eruption) of the deciduous dentition period (Stage II), middle stage (m2 eruption) of the deciduous dentition period (Stage III), late state (eruption of 20 deciduous teeth) of the deciduous dentition period (Stage IV), mixed dentition period (Stage V), and permanent dentition period (Stage VI). Each skull was mounted on a Kraniophor in such a way that the auriculoorbital (Frankfurt) plane was positioned vertical to the horizontal plane and photographed at a focal distance of 40 cm. Using the Frankfurt plane as a base line, the vertical distances to the lowest point of the postglenoid process (a-A), to the deepest point of the mandibular fossa (b-B), and to the mid-point of the articular tubercle (c-C) were measured. The distances from various points of the mandibular fossa to the articular surface of the temporal bone were measured at the level of the Frankfurt plane. The results may be summarized as follows: The length of the postglenoid process as measured from the Frankfurt plane was 0.58 mm at Stage I and 0.75 mm at Stage II. It increased by 0.6-1.0 mm at each developmental stage. By Stage VI, it had increased to 3.85 mm (six- to seven-fold increase from the initial value). The anteroposterior width of the postglenoid process remained almost unchanged throughout the developmental stages. The growth of the articular structures of the temporal bone from the preeruption to deciduous dentition period increased 73% in the total anteroposterior dimension (5.22 mm) and 44% in the total vertical dimension (3.32 mm). The vertical dimension of the mandibular fossa began to rapidly increase following the eruption of the deciduous first molars.

Adolescent↗
PubMed1995

Influence of aging on the oxidative and conjugative metabolism of propranolol.

The influence of aging on the hepatic metabolism of propranolol, i.e. conjugation, side-chain oxidation and ring oxidation, was investigated in 32 in-patients aged 30 to 84 yrs. Plasma propranolol concentration and main urinary metabolites [propranolol glucuronide (PPLG), naphthoxylactic acid (NLA), and 4-hydroxypropranolol (40HP)] were determined after a single oral dose of 20 mg propranolol. There were significant correlations between age and 1) maximum propranolol concentration, 2) area under the plasma concentration-time curve, and 3) elimination half-life. The apparent oral clearance of propranolol was inversely correlated with age. Partial metabolic clearance (PMC) to 40HP (ring oxidation) and PMC to NLA (side-chain oxidation) were significantly correlated with age, while PMC to PPLG was not. These observations suggest that there are age-related reductions in two oxidizing capacities, while there is no significant influence of aging on the conjugating capacity. The age-related reduction in oral clearance of propranolol may be mainly caused by the decline in the capacity of two different oxidation pathways.

Adrenergic beta-Antagonists↗
PubMed1994

Comparison of the pharmacokinetics, pharmacodynamics, and safety of oral (Catapres) and transdermal (M-5041T) clonidine in healthy subjects.

The pharmacokinetic as well as pharmacodynamic properties of a transdermal clonidine, M-5041T (M) and its safety were compared with those of oral clonidine, Catapres (Nippon Boehringer Ingelheim, Hyogo, Japan). One patch of M containing 6 mg of clonidine was applied on the right chest for 3 days or one tablet of Catapres (.075 mg) was given orally every 12 hours for 3 days in eight healthy subjects. The study was conducted by a crossover design with 14 to 16 days' interval between the cross-over. Blood and urine samples for clonidine concentration were obtained, and blood pressure (BP) was measured for a 168-hour period after application of M and for a 96-hour period after initiation of Catapres therapy. Plasma concentration of clonidine increased gradually after application of M and decreased gradually after removal, whereas this parameter increased rapidly during the absorption phase and decreased rapidly in the elimination phase after each dosage of Catapres. Elimination half-life of clonidine after removal of M was significantly greater than that after the final dosage of Catapres. No significant difference was observed in maximum plasma concentration or area under the plasma concentration-time curve between the two trials. The BP lowering effects of M and Catapres did not differ significantly. Adverse symptoms occurred more frequently during Catapres therapy than during treatment with M. Most of these symptoms were observed when plasma clonidine concentration was relatively higher in each trial. These results suggest that M is effective for the treatment of hypertension with a lower incidence of adverse symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1994

Renal clearance of lomefloxacin is decreased by furosemide.

The interaction between lomefloxacin, a new quinolone, and furosemide, a loop diuretic, has been examined. Oral lomefloxacin 200 mg and furosemide 40 mg were given together or separately to 8 healthy subjects, and blood and urine samples were obtained over the following 12 h. The plasma concentrations of lomefloxacin following coadministration with furosemide were higher than after lomefloxacin alone and its AUC was increased, and its total and renal clearances were decreased. No change in the pharmacokinetics of furosemide was found after coadministration of lomefloxacin. As quinolones and furosemide are reported to be excreted in urine by the renal tubular anion transport system, the present results suggest that the renal tubular secretion of lomefloxacin is diminished by furosemide. It is not clear whether this pharmacokinetic interaction might be clinically important.

Adult↗
PubMed1994

Time-dependent change in the toxic effects of amikacin on renal functions.

The present study was undertaken to examine whether there was a time-dependent change in the toxic effects of amikacin, an aminoglycoside, on renal functions. Male Wistar rats were maintained under conditions of light from 7 am to 7 pm and dark from 7 pm to 7 am. Amikacin (1.2 g/kg) was injected intraperitoneally to animals at 4 am, 10 am, 4 pm or 10 pm. Glomerular function estimated by creatinine clearance (Clcr) and tubular function estimated by urinary excretion of a loop diuretic, furosemide, which was excreted in urine mainly by tubular secretion, were determined before and 24 hours after amikacin injection. The values of these parameters were reduced by amikacin at each observation point. The magnitude of these decrements was greatest at 4 pm both for Clcr and urinary furosemide excretion. These results suggest that the toxic effects of amikacin on renal glomerular and tubular functions vary with its time of administration.

Amikacin↗
PubMed1994

Daily variation in the urinary excretion of furosemide in young and aged rats.

We have recently demonstrated that the time-dependent difference in urinary excretion of furosemide, a loop diuretic, diminishes during the aging process and disappears by 18 months of age in rats. The present study was undertaken to examine whether the amplitude of the daily variations in the urinary excretion of furosemide or their pattern, or both, are influenced in aged animals. Young (3 months of age) and aged (30 months of age) Wistar rats were maintained under conditions of light from 7 am to 7 pm and dark from 7 pm to 7 am. Furosemide (30 mg/kg) was given orally at 4 am, 8 am, 12 am, 4 pm, 8 pm or 12 pm. Urine was collected for 8 hours after furosemide administration and urinary excretion of furosemide was determined. There were significant daily variations in the urinary furosemide and the urine volume with the peak at 8 am and the trough at 12 pm in both groups of rats. The differences in these parameters between the 8 am and 12 pm trials were significantly smaller in the aged than in the young rats. These results suggest that the age-related alteration in the time-dependent phenomenon of furosemide is caused by the decreased amplitude of the daily variation in the urinary furosemide excretion and its diuretic effect.

Age Factors↗
PubMed1994

Effect of angiotensin II type 1 receptor antagonist on urinary prostaglandin E2 excretion following furosemide in rats.

The present study was undertaken to examine an effect of an angiotensin II type 1 (AT1) receptor antagonist on urinary prostaglandin E2 (PGE2) excretion following furosemide, a loop diuretic, in rats. Furosemide (30 mg/kg) was given orally with or without pretreatment with derapril (30 mg/kg), an angiotensin converting enzyme inhibitor, TCV-116 (1 mg/kg), an AT1 receptor antagonist, or losartan (10 mg/kg), another AT1 receptor antagonist. The 6-hour urine was collected following furosemide, and the urinary excretion of PGE2 was determined. The urinary PGE2 increased significantly following furosemide alone. However, such a furosemide-induced increase was not observed with pretreatment with derapril, TCV-116 or losartan. These results suggest that the increased urinary excretion of PGE2 following furosemide is blunted by derapril, TCV-116 and losartan. As TCV-116 and losartan are selective AT1 receptor antagonists, the effect of furosemide on renal PGE2 production, as reflected by the urinary PGE2, might be mediated by an activation of AT1 receptors.

Angiotensin II↗