Biomedical subjects

A Fujimura

Publications and source records attributed to A Fujimura.

At least 181 records · Page 10Linked to original sources

PubMed1992

Chronopharmacology of furosemide in the elderly.

The authors have previously reported the time-dependent change in the diuretic effects of furosemide, a loop diuretic agent, in young and middle-aged subjects. The current study was undertaken to examine an influence of aging on this chronopharmacologic phenomenon. Ten milligrams furosemide was given intravenously to 12 elderly subjects (greater than 70 years of age) at 9:00 AM (day trial) or at 9:00 PM (night trial) by a cross-over design. One-hour urine samples were collected for 3 hours after each administration, and urine volume and urinary excretions of sodium and furosemide were determined. Urine volume and urinary sodium excretion increased after furosemide administration. Contrary to the findings in the young and middle-aged subjects, no significant differences were observed in these parameters at any observation period between the day and night trials in the elderly subjects. Urinary furosemide excretion of the day and night trials did not significantly differ. These results suggest that the chronopharmacologic profiles of furosemide are altered in the elderly.

Aged↗

PubMed1992

Effect of treatment at night with S-1452, a thromboxane A2 receptor antagonist, on the morning rise in platelet aggregation.

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 A2 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.

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

PubMed1992

Time-dependent change in the effect of probucol in subjects with elevated cholesterol.

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.

Aged↗

PubMed1992

Influence of renal denervation on chronopharmacology of furosemide in rats.

Our previous studies have suggested that the adrenergic nervous system is involved in the mechanism responsible for the time-dependent change in the urinary excretion of furosemide in rats. To examine a potential role of renal nerves in this phenomenon, renal denervation or sham operation was performed using unilaterally nephrectomized rats. Furosemide (30 mg/kg) was given orally at 12 am or 12 pm. Urine was collected for 8 hours after furosemide dosing, and urinary excretions of furosemide and sodium were determined. Urinary furosemide excretion and diuretic effects of the agent (urine volume and urinary sodium) were significantly greater at 12 am than at 12 pm in the sham-operated group of rats. However these administration time-dependent changes in urinary furosemide and its diuretic effects disappeared in the renal-denervated group of animals. These results suggest that the renal nerves contribute to the time-dependent changes in the urinary excretion of furosemide and its subsequent diuretic effects.

Administration, Oral↗

PubMed1992

Daily variations in platelet aggregation and adhesion in healthy subjects.

Platelet aggregation is known to show a morning rise. The present study was undertaken to examine whether platelet aggregation and adhesion show a peak in the afternoon. Platelet aggregation stimulated by 4 microM of adenosine diphosphate, 1 micrograms/ml of collagen, 4 microM of epinephrine and 0.5 mM of arachidonic acid, and platelet adhesion determined by platelet retention on a glass bead column were measured for a period of 28-hour with an interval of 4 hours in 6 healthy subjects. Platelet aggregation in response to 4 different aggregating agents showed a bimodal daily variation with peaks in the morning and in the afternoon. However platelet adhesion only showed a peak in the morning. Previous studies have demonstrated the increases in the onset of acute myocardial infarction (MI) in the morning and afternoon periods. As enhanced platelet aggregation is involved in the development of acute MI, the present study suggests that the rise in platelet aggregation contributes to the increase in acute MI in the morning and in the afternoon. The present study suggests that the enhancement of platelet adhesion, which might be involved in thromboembolic events, may be another triggering factor for the onset of acute MI.

Adenosine Diphosphate↗

PubMed1992

Chronopharmacological study of furosemide; (IX). Influence of continuous norepinephrine infusion.

Our previous studies have suggested that the adrenergic nervous system is involved in the mechanisms responsible for the time-dependent changes in the effects of furosemide in rats. To examine this hypothesis further, norepinephrine (150 micrograms/kg/hr) or its vehicle alone was infused subcutaneously by osmotic minipumps. Furosemide (30 mg/kg) was given orally at 12 am or 12 pm. Urine was collected for 8 hours after the agent, and urinary excretions of sodium and furosemide were determined. Urine volume and urinary excretion of sodium and furosemide were significantly greater at 12 am than at 12 pm in the vehicle-infused group of rats. However these administration-time-dependent changes in the effects of furosemide and its urinary amount disappeared in the norepinephrine-infused group of animals. Since chronic norepinephrine infusion is considered to disturb the axis of adrenergic nervous system, these data support the hypothesis concerning the mechanisms of this chronopharmacological phenomenon of furosemide.

Administration, Oral↗

PubMed1992

Urinary excretion of furosemide in rats with HgCl2-induced acute renal damage.

To examine the influence of mercuric chloride (HgCl2)-induced acute renal damage on urinary excretion of furosemide, HgCl2 (1 mg/kg) or its vehicle alone was given intraperitoneally to Wistar rats. The following two experiments were done. Study I: Three percent body weight (b.w.) of 1% NaCl solution or furosemide (30 mg/kg) in 3% b.w. of 1% NaCl solution was given orally before and after HgCl2 treatment, and an 8-hour urine was collected. Study II: Furosemide (30 mg/kg) was given orally, and blood samples were obtained at 1, 2, 3, 4, 6 and 8 hours after administration. Urinary excretion of N-acetyl-beta-D-glucosaminidase increased, and urine volume and urinary excretions of furosemide and sodium decreased in the HgCl2-treated rats. There were significant correlations between the urinary furosemide and its diuretic effects. Regression lines after HgCl2 were significantly different from those before treatment. The values of absorption as well as elimination rate constant were smaller, while the time to maximum concentration and the elimination half-life were longer in the HgCl2-treated rats compared to vehicle-treated animals. These results suggest that the urinary excretion of furosemide and the responsiveness of renal tubular cells to this agent are impaired in rats with HgCl2-induced acute renal damage.

Acute Kidney Injury↗

PubMed1992

Influence of adrenalectomy on chronopharmacological phenomenon of furosemide in rats.

The role of adrenal corticoids in the time-dependent changes in the effects of furosemide was examined. Furosemide (30 mg/kg) was given orally to adrenalectomized or sham-operated rats at 12 a.m. or 12 p.m. Urine volume and urinary excretion of sodium and furosemide for 8 hr were significantly greater at 12 a.m. than at 12 p.m. in the sham-operated rats. However, such time-dependent changes in these parameters disappeared in the adrenalectomized animals. These findings indicate that adrenal corticoids are directly or indirectly involved in this event.

Adrenal Cortex Hormones↗

PubMed1992

Chronopharmacology of probucol in mice.

Mice were maintained under conditions of light from 7 a.m. to 7 p.m. and dark from 7 p.m. to 7 a.m. Probucol was given orally to these animals once daily at 10 a.m. or 10 p.m. for 7 days. Blood samples for serum cholesterol were obtained at 24 hours after the final dosage. Blood samples for plasma probucol were obtained just before and at 3, 6, 12, 24, 48, 72, 96 and 120 hours after the final dosage. The cholesterol lowering effect of the agent at 10 p.m. was greater than that at 10 a.m. Plasma probucol concentrations of the two trials did not differ at any observation point. These data suggest that the effect of probucol varies with its time of administration. This might not be caused by a time-dependent change in plasma probucol concentration.

Administration, Oral↗

PubMed1992

Influence of DOCA treatment on administration-time-dependent changes in the effects of furosemide in saline-loaded rats.

We have previously found that the administration-time-dependent change in the effects of furosemide, a loop diuretic agent, is observed in normal rats. The present study was undertaken to examine whether an alteration in this phenomenon occurs in rats with DOCA-saline hypertension. Unilateral nephrectomized rats were divided into three groups. The first group (DOCA-saline) received a 50 mg DOCA tablet intraperitoneally and drank 1% NaCl solution. The other two groups were given sham operations. A 1% NaCl solution was given as drinking water to the second group (control-saline), while tap water was given to the third group (control-water). Furosemide (30 mg/kg) was given orally to each group at 12 a.m. or 12 p.m. Urine was collected for 8 hours after the agent, and urinary excretion of sodium and furosemide were determined. Urine volume and urinary excretion of sodium and furosemide following the agent were significantly greater at 12 a.m. than at 12 p.m. in the control-water and control-saline groups. However, the administration-time-dependent changes in these parameters disappeared in the DOCA-saline rats. These results suggest that the mode of the administration-time-dependent changes in the effects of furosemide is altered in the DOCA-saline hypertensive rats.

Animals↗

PubMed1992

Chronopharmacology of furosemide in rats with amikacin-induced acute renal damage.

To examine the influence of amikacin-induced acute renal damage on the urinary excretion of furosemide and the time-dependent variation in the urinary amount of the agent, amikacin (1.2 g/kg) was given intraperitoneally to Wistar rats. Study I: Three percent b.w. of 1% NaCl solution was given orally before and after amikacin treatment, and an 8-hour urine for N-acetyl-beta-D-glucosaminidase (NAG) was collected. Study II: Furosemide (30 mg/kg) in 3% b.w. of 1% NaCl solution was given orally at 12 a.m. or 12 p.m. before and after amikacin treatment, and an 8-hour urine for sodium and furosemide was collected. Following amikacin treatment, urinary excretion of NAG increased, while urine volume and urinary excretion of sodium and furosemide decreased. Urinary excretion of furosemide and its diuretic effects were significantly greater at 12 a.m. than at 12 p.m. before and after treatment. However the time-dependent differences in these parameters were diminished by amikacin treatment. These results suggest that the urinary excretion of furosemide is reduced and the extents of the time-dependent variation in the urinary furosemide and its diuretic effects are altered in rats with amikacin-induced renal damage.

Acetylglucosamine↗

PubMed1992

Daily variation in the effects of furosemide in rats.

Daily variation in the effects of furosemide, a loop diuretic agent, was examined in Wistar rats maintained under conditions of light from 7 a.m. to 7 p.m. and dark from 7 p.m. to 7 a.m. Furosemide (30 mg/kg) was given orally at 12 p.m., 4 a.m., 8 a.m., 12 a.m., 4 p.m. or 8 p.m. Urine was collected for 8 hr after furosemide administration, and urinary excretions of sodium and furosemide were determined. There were significant daily variations in the urine volume and urinary excretions of sodium and furosemide with a peak at 8 a.m. and a trough at 12 p.m. Significant correlations were observed between the urinary amount of furosemide and its diuretic effects (urine volume and urinary sodium excretion). These results suggest that the diuretic effects of furosemide show daily variations which are, at least in part, caused by the daily variation in the urinary excretion of furosemide.

Animals↗

PubMed1992

Diurnal effect on caffeine acetylation phenotyping: a preliminary report.

The present study examined whether caffeine acetylation phenotype could be altered by its time of administration. Caffeine was given orally to nine healthy subjects at 10 a.m. and 10 p.m. and acetylation phenotype was determined by measuring the major metabolites of caffeine in urine. The results showed that acetylation phenotypes determined in the day trial were not different from those determined during the night trial.

Acetylation↗

PubMed1992

The influence of diltiazem versus cimetidine on propranolol metabolism.

The present study was undertaken to examine whether the inhibitory effect of diltiazem on the metabolism of propranolol differs from that of cimetidine. Six healthy male volunteers received a single oral dose of 20 mg propranolol with pretreatment with placebo, 60 mg diltiazem, or 400 mg cimetidine three times daily for 4 days. Diltiazem and cimetidine increased the area under the concentration (AUC) of propranolol and its glucuronide. Cimetidine also increased the urinary excretion of propranolol glucuronide. There were no significant differences in the AUC of 4-hydroxypropranolol (4OHPPL) and its conjugates or the urinary excretion of conjugated 4OHPPL. Diltiazem increased the AUC of naphthoxylactic acid (NLA) and the urinary excretion to NLA. After cimetidine pretreatment, there was the trend toward a decrease in the partial metabolic clearance to 4OHPPL and a significant decrease in that of NLA. These results suggest that diltiazem and cimetidine inhibit the oxidation pathways of propranolol in different manners. Cimetidine might inhibit both oxidative pathways to 4OHPPL and NLA, whereas diltiazem might not inhibit the pathway to NLA.

Adult↗

PubMed1992

Effect of diltiazem on the pharmacokinetics of MPC-1304, a new calcium channel blocker.

The effect of diltiazem pretreatment on the pharmacokinetics and pharmacodynamics of MPC-1304, a new calcium channel blocker, were evaluated in six healthy male volunteers. Placebo or diltiazem 60 mg was given orally three times daily for 3 days in a double-blind crossover method. MPC-1304 10 mg was administered orally two times at an interval of four weeks as a washout period. Diltiazem significantly increased the maximum plasma level (Cmax) and the area under the plasma concentration-time curve (AUC) of MPC-1304 from control values (3.0 +/- 1.5 to 10.2 +/- 4.8 ng/ml, p less than 0.05, and 11.0 +/- 3.8 to 36.0 +/- 15.6 ng.h/ml, p less than 0.01, respectively) without any changes of t1/2. In the case of the major active metabolite, side chain reduced form (MI), Cmax, AUC, and t1/2 were significantly increased by diltiazem as follows: Cmax, 60.7 +/- 21.1 to 171.4 +/- 73.6 ng/ml, p less than 0.05; AUC, 317.6 +/- 62.6 to 1,334.9 +/- 563.6 ng.h/ml, p less than 0.01; t1/2, 2.8 +/- 0.7 to 3.9 +/- 0.6 h, p less than 0.01. Diltiazem pretreatment slightly, but not significantly decreased blood pressure after MPC-1304 dosing. The inhibition of hepatic metabolism on MPC-1304 may explain the significant changes in pharmacokinetics of MPC-1304 after diltiazem pretreatment.

Administration, Oral↗

PubMed1991

Chronotherapy of trichlormethiazide in hypertensive patients.

Circadian influence of trichlormethiazide on serum electrolyte levels, lipid levels, and glucose levels were evaluated in 12 hypertensive patients. One tablet of trichlormethiazide (2 mg) was given once a day at 7:00 AM or 7:00 PM for 8 weeks. The study was done by a crossover design. Twenty-four-hour urine was collected, and fasting blood samples were obtained during the control period and at the end of each treatment period. The 24-hour urine level increased slightly after treatment with trichlormethiazide in the morning and evening trials. Urinary excretion of sodium also increased slightly in the morning trial and increased significantly in the evening trial. Serum concentrations of potassium and chloride decreased, and serum uric acid level increased after trichlor-methiazide treatment. No significant difference was observed in these parameters between morning and evening trials. Fasting blood glucose levels increased after trichlormethiazide treatment. The increment in blood glucose levels was greater in the evening trial than in the morning trial. These data indicate that the influence of trichlormethiazide on glucose tolerance might vary with its administration time.

Adult↗

PubMed1991

The effect of diltiazem on hepatic drug oxidation assessed by antipyrine and trimethadione.

The effect of pretreatment for 3 days with diltiazem 60 mg three times a day on the pharmacokinetics of 500-mg antipyrine and 250-mg trimethadione was studied in six healthy male subjects. Diltiazem decreased the total body clearance from 34.0 +/- 8.0 to 28.6 +/- 6.1 mL/min (P less than .01), and prolonged the elimination half-life from 12.6 +/- 3.0 to 14.3 +/- 2.5 hours (P less than .01) of antipyrine without any changes in volume of distribution. The cumulative renal excretion (% dose) of antipyrine was significantly increased from 2.23 +/- 0.73 to 2.78 +/- 0.83% (P less than .05). Clearances of production for three major antipyrine metabolites, norantipyrine (4.31 +/- 1.64 to 3.50 +/- 1.28 mL/min, P less than .01), 3-hydroxymethylantipyrine (4.67 +/- 1.63 to 3.82 +/- 1.34 mL/min, P less than .01) and 4-hydroxyantipyrine (10.47 +/- 3.41 to 8.16 +/- 2.82 mL/min, P less than .01) were reduced significantly by diltiazem. On the other hand, diltiazem did not produce any significant changes in pharmacokinetic parameters of trimethadione and plasma concentration ratio, oxidative major metabolite of trimethadione to trimethadione itself. These results suggest that other drugs metabolizing the same hepatic oxidative pathways as antipyrine, may be influenced by diltiazem.

Adult↗

PubMed1991

Chronopharmacology of trichlormethiazide in rats; (II). Examination in aged rats.

We have previously demonstrated a time-dependent variability in the diuretic effects of trichlormethiazide, a thiazide diuretic agent, in young rats. The study suggested that the time-dependent variations in urinary trichlormethiazide and susceptibility of renal tissues to the agent might be involved in this phenomenon. The present study was undertaken to test a hypothesis that such a daily variation in the effects of trichlormethiazide is blunted by age. Trichlormethiazide (0.5 and 2.0 mg/kg) was given orally at 1200 hrs (day trial) or at 2400 hrs (night trial) in young (10-11 week old) and aged (23-24 month old) Wistar rats. Urine was collected for 8 hours after the agent and urinary excretions of sodium, chloride and trichlormethiazide were determined. Urine volume and urinary excretions of sodium, chloride and trichlormethiazide following the agent were significantly greater at 1200 hrs than at 2400 hrs in the young rats. However these administration time-dependent changes in the effects of trichlormethiazide and its urinary amount diminished in the aged rats. In the day and night trials, there were significant correlations between urinary trichlormethiazide and its effects (urine volume, urinary sodium and chloride) in both groups of rats. The regression lines in each parameter of two trials differed in the young, but not in the aged group of rats. These data indicate that the mode of the time-dependent changes in the effects of trichlormethiazide is altered in aged Wistar rats. Dampening of the time-dependent variations in urinary trichlormethiazide and susceptibility to the agent might be involved in these chronopharmacological alterations in aged rats.

Administration, Oral↗