Biomedical subjects

A Fujimura

Publications and source records attributed to A Fujimura.

At least 199 records · Page 11Linked to original sources

PubMed1991

Chronopharmacological study of furosemide; (VIII) influence of feeding restriction.

We have previously reported that a time-dependent variation is observed in the diuretic effect of furosemide and the light-dark cycle is a potent zeitgeber for this chronopharmacological phenomenon of the agent in rats. The present study was undertaken to examine whether a time of food intake is another zeitgeber for this event. In study I, rats were maintained with free access to food for 3 weeks. Furosemide (30 mg/kg) was given orally at 12 am or 12 pm. Urine was collected for 8 hours after the agent and urinary excretion of sodium and furosemide were determined. Thereafter, these rats were maintained under a daytime-restricted feeding schedule (9 am-11 am) for 3 weeks (study II) and a night-time-restricted feeding schedule (9 pm-11 pm) for 3 weeks (study III). The identical protocol of study I was repeated at the end of study II and III. Diuretic effect of furosemide and its urinary excretion were significantly greater at 12 am than at 12 pm in study I and III. However such an administration time-dependent change in the effect of furosemide and its urinary amount disappeared in study II. These data indicate that a time of food intake is another potent zeitgeber for the time-dependent variation in the diuretic effect of furosemide.

Animals↗

PubMed1991

Chronopharmacology of trichlormethiazide in rats.

Trichlormethiazide was given orally at 1200 hrs or 2400 hrs to rats. Its diuretic effects were greater at 1200 hrs than at 2400 hrs. There were significant correlations between urinary trichlormethiazide and its effects in both trials. The regression lines of two trials did differ. These findings indicate that the effects of trichlormethiazide vary with its administration time. Time-dependent variations in urinary trichlormethiazide and susceptibility to the agent might be involved in this phenomenon.

Administration, Oral↗

PubMed1991

Chronopharmacology of the new uricosuric diuretic S-8666 in rats.

A new loop diuretic with uricosuric activity, 6,7-dichloro-5-(N,N-dimethylsulfamoyl)-2,3-dihydro-2-benzofuran carboxylic acid (S-8666), was given orally at 12:00 a.m. or 12:00 p.m. in rats. The diuretic of S-8666 and the urinary excretions of the drug and its active metabolite S-8680 (N-demethyl S-8666) were greater at 12:00 a.m. than at 12:00 p.m. Thus, the present study indicates that the diuretic effects of S-8666 varies with its administration time. Time-dependent variations in the amount of urinary excretions of S-8666 and S-8680 might be involved in the mechanisms for this phenomenon.

Animals↗

PubMed1991

Diurnal variation in the diuretic effects of nitrendipine in saline loaded rats.

We have previously reported that the responsiveness of blood pressure to nitrendipine, a dihydropyridine calcium antagonist, varies with its time of administration. The present study was undertaken to examine whether the diuretic effects of the agent also show diurnal variation. Nitrendipine was given orally at 12 a.m. or 12 p.m. to rats, and urine was collected for 8 hours after administration. The urine volume and urinary sodium excretion were greater at 12 p.m. than at 12 a.m. These data indicate that the cardiovascular as well as renal effects of nitrendipine vary with its time of administration.

Animals↗

PubMed1991

Influence of chronic lithium treatment on urinary amount of furosemide in rats.

The present study was undertaken to examine whether the urinary amount of furosemide is influenced by chronic lithium treatment. LiCl at 2 mEq/kg/day in 1 ml vehicle (5% glucose solution) or 1 ml of vehicle alone was injected intraperitoneally for 8 days into Wistar rats. On day 8, 30 mg/kg of furosemide in 3% body weight of 1% NaCl was given orally, and urine was collected for 6 hr after dosage. The urinary amount of furosemide in the Li-treated rats was significantly lower than that in the control animals [Li group (n = 12): 514 +/- 75 (mean +/- S.E.) vs. control group (n = 12): 916 +/- 85 micrograms/kg/6 hr, P less than 0.01]. This finding indicates that pharmacokinetic alterations of furosemide might occur during chronic treatment with lithium.

Administration, Oral↗

PubMed1991

Chronopharmacology of the new uricosuric diuretic S-8666 in rats: (II). Examination in aged rats.

We have previously demonstrated a time-dependent variability in the diuretic effects of S-8666, a new loop diuretic with uricosuric activity, in young rats. The present study was undertaken to determine whether such a daily variation in the effects of the agent exists in aged rats. S-8666 (30 and 90 mg/kg) was orally given at 12:00 a.m. (day trial) or at 12:00 p.m. (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, S-8666 and its active metabolite S-8680 were determined. Urinary excretions of volume and sodium following S-8666 at 12:00 a.m. were greater than those at 12:00 p.m. in the young and aged animals. Urinary excretions of S-8666 and S-8680 were also greater in the day trial compared to those in the night trial in both groups of rats. In the day and night trials, there were significant correlations between urinary S-8666 + S-8680 and the diuretic effects in both groups of rats. These findings indicate that the diuretic effects of S-8666 also vary with its time of dosing in aged rats. The time-dependent variations in urinary S-8666 and S-8680 might be involved in this phenomenon.

Aging↗

PubMed1991

Chronopharmacology of trichlormethiazide in rats: (III). Influence on serum triglyceride and glucose.

Trichlormethiazide was given orally to rats at 10 a.m. or 10 p.m. for 14 days. The diuretic effects of the agent at 10 a.m. were greater than those at 10 p.m. on day 14. Serum concentrations of triglyceride and glucose increased in both trials. The increments in these parameters were enhanced following trichlormethiazide at 10 a.m. These data indicate that the diuretic effects of trichlormethiazide and its untoward influences on serum metabolic parameters might vary with the administration time during a repeated therapy.

Animals↗

PubMed1991

Influence of repeated administration of lithium on urinary excretion of prostaglandins in rats.

The present study was undertaken to examine whether urinary excretions of prostaglandins increase by repeated administration of a non-toxic dose of lithium. Our previous study demonstrated that 2 mEq/kg/day of lithium chloride (LiCl) is not a toxic dose; and therefore, this dose of LiCl in 1 ml vehicle (5% glucose solution) or 1 ml of vehicle alone was injected intraperitoneally for 7 days into Wistar rats. On day 7, 3% body weight of 1% NaCl solution was given orally; and urine for the determination of PGE2 and 6-keto-PGF1 alpha, a metabolite of PGI2, was collected for 6 hr after dosage. Thereafter, blood samples for measuring plasma renin activity (PRA) were obtained. The urinary amounts of PGE2 and 6-keto-PGF1 alpha in the Li-treated rats were significantly greater than those in the control animals. The values of PRA did not significantly differ between the two groups of rats. These findings indicate that the production of prostaglandins, including those of PGE2 and PGI2, are enhanced during repeated administration of a non-toxic dose of lithium. The enhanced production of prostaglandins might not be mediated through the activated renin-angiotensin system.

6-Ketoprostaglandin F1 alpha↗

PubMed1991

Metabolites of antihypertensive drugs. An updated review of their clinical pharmacokinetic and therapeutic implications.

Many antihypertensive drugs are extensively metabolised in humans. Since some metabolites are active and may therefore contribute to the pharmacological activity of the parent drugs, knowledge of the pharmacokinetic properties of active metabolites is important for understanding the overall effects of drugs. Four categories of antihypertensive drugs with active metabolites are dealt with, with selected examples described in some detail. First, drugs with effects relying totally on active metabolites include agents such as methyldopa, cadralazine and many angiotensin converting enzyme (ACE) inhibitors. Secondly, those with effects primarily due to active metabolites include drugs such as triamterene and spironolactone. Thirdly, agents with effects primarily due to the parent drug, but with active metabolites providing significant contributions to the overall pharmacological effect, include drugs such as indoramin, alprenolol, acebutolol, diltiazem and verapamil. Lastly, agents with pharmacological effects with only minor (if any) contributions from active metabolites include drugs such as propranolol, metoprolol, carteolol and others.

Aging↗

PubMed1991

Pharmacokinetics of pranoprofen in the elderly.

The present study was undertaken to examine whether the pharmacokinetic profiles of pranoprofen, a non-steroidal anti-inflammatory drug, are altered in the elderly. Pranoprofen (75 mg) was given orally to six young and seven elderly subjects, and blood sample was obtained 0.5, 1, 2, 3, 5, 8 and 10 h after administration of the drug. The elimination half-life of pranoprofen was significantly longer and its plasma clearance was significantly lower in the elderly than those levels in the young subjects. The area under the plasma concentration-time curve in the elderly group was significantly greater than that in the younger group. No significant difference was observed in the maximum plasma concentration or the time to maximum plasma concentration between the two groups. These data indicate that the pharmacokinetic profiles of pranoprofen are altered in the elderly.

Administration, Oral↗

PubMed1991

Chronotherapeutic study of furosemide in hypertensive subjects: a preliminary report.

In the present study, circadian influences of furosemide on serum electrolytes, lipids and glucose were evaluated in ten hypertensive subjects. A retard capsule (40 mg) of furosemide was given once a day in the morning (07 h 00) or in the evening (19 h 00) for eight weeks. The study was done through a cross-over 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 volume was slightly increased by the repeated administration of furosemide in the morning and evening trials. Urinary excretion of sodium also slightly increased in the morning trial and significantly increased in the evening trial. Serum concentrations of potassium and chloride decreased, while serum uric acid and triglyceride were increased by furosemide treatment. No significant difference was observed in these parameters between morning and evening trials. Fasting blood glucose increased following furosemide. The increment in this parameter was greater in the evening trial than in the morning trial. These findings indicated that the influence of furosemide on glucose tolerance might vary with its time of administration.

Adult↗

PubMed1990

Clinical pharmacology of dilevalol (i.v.). Influence of hepatic and renal functions on the disposition of dilevalol and atenolol in hypertensive subjects.

Dilevalol (100 mg) or atenolol (50 mg) was given orally in 13 subjects with essential hypertension. Two trials were done by a single-blind, crossover design with an interval of 6 days. Blood samples for drug concentrations were taken for a period of 24 hours after dosage. A retained percentage of indocyanine green dye at 15 minute (ICG R15) reflecting hepatic function and a creatinine clearance (CLCR) reflecting renal function were determined in each subject during observation period. A significant correlation was observed between the ICG R15 and the area under the plasma concentration-time curve (AUC) of dilevalol, while there was no significant correlation between the CLCR and any pharmacokinetic parameter of the agent. In contrast to dilevalol, significant correlations were observed between the CLCR and AUC or elimination half-life of atenolol. However, there was no significant correlation between the ICG R15 and any pharmacokinetic parameter of atenolol. These data indicate that the disposition of dilevalol is influenced by hepatic rather than by renal function while that of atenolol is altered by renal function.

Administration, Oral↗

PubMed1990

Influence of captopril on urinary excretion of furosemide in hypertensive subjects.

Influence of captopril on urinary excretion of furosemide was examined in a placebo-controlled, crossover design. Furosemide (20 mg) was injected intravenously in eight hypertensive subjects with pretreatment with captopril (25 mg) or matching placebo. Urine samples for furosemide and sodium were collected during the following intervals: -60-0, 0-60, 60-120, and 120-180 minutes after furosemide. Blood samples for plasma renin activity (PRA) and angiotensin II (AII) were obtained, and blood pressure was measured at -60, 0, 60, 120, and 180 minutes after furosemide. No significant difference was observed in urinary excretion of furosemide, volume or sodium between these trials. Although PRA increased following furosemide with captopril, as predicted plasma AII did not increase. Blood pressure significantly decreased following the combined therapy, but not furosemide alone. These data indicate that the urinary excretion of furosemide and its subsequent diuretic effects are not influenced by captopril.

Adult↗

PubMed1990

Circadian influence on effect of propranolol on exercise-induced tachycardia in healthy subjects.

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 (t 1/2) 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1990

Effect of furosemide on angiotensin II-mediated prostaglandin I2 production in hypertensive subjects.

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-PGF1 alpha (a metabolite of PGI2) and PGE2, PRA and AII was increased following furosemide without captopril pretreatment. The rises in urinary 6-keto-PGF1 alpha 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-PGF1 alpha, was mediated by an action of AII.

6-Ketoprostaglandin F1 alpha↗

PubMed1990

Chronopharmacological study of furosemide; (V). Influence of pretreatment with 6-hydroxydopamine.

Our previous indirect evidences suggested that the adrenergic nervous system is involved in the mechanisms responsible for the time-dependent changes in the effects of furosemide in Wistar rats. In the present study, the role of this system was examined more directly by means of 6-hydroxydopamine-induced sympathectomy. Thirty mg/kg of 6-hydroxydopamine hydrobromide (6-OH-DA) (n = 9) or its vehicle alone (n = 9) was injected intra-arterially (i.a.) twice in Wistar rats. Furosemide (5 mg/kg) was administered i.a. at 1000 hrs (03HALO*) or at 2200 hrs (15HALO). Urine was collected for 60 min after the drug and urinary excretion of sodium and furosemide were determined respectively. Urine volume and urinary excretion of sodium and furosemide were significantly greater at 1000 hrs (03HALO) than at 2200 hrs (15HALO) in the vehicle-injected rats as observed in the previous study. However these administration-time-dependent changes in the effects of furosemide disappeared in the rats with 6-OH-DA. Thus, the present study provides more direct evidence and supports our original hypothesis concerning the mechanisms of this chronopharmacological phenomenon of the agent. Since 6-OH-DA does not penetrate the central nervous system from the blood stream, the present data also indicate that the peripheral adrenergic system is involved in this event.

Animals↗

PubMed1990

Chronopharmacological study of furosemide; (VII). Influence of repeated administration on biochemical parameters in blood.

The present study was undertaken to examine whether influences of furosemide on biochemical parameters vary with its time of administration in Wistar rats. Rats were maintained under conditions of light (0700-1900 hrs) and dark (1900-0700 hrs). Furosemide (30 mg/kg) or vehicle (5% glucose) was given orally at 1000 hrs (day trial) or at 2200 hrs (night trial) for 14 days. Water and food intakes were measured, and urine was collected for 24 hours following the final dosage in each group. Thereafter, blood samples were obtained. Water intake and urinary excretions of volume, sodium and chloride increased by furosemide treatment. The increments in these parameters were greater in the day trial than in the night trial. Food intake did not change. The serum concentration of chloride was decreased by furosemide. The decrement in this parameter was enhanced in the day trial. The influence of furosemide on other biochemical parameters (sodium, potassium, creatinine, calcium, inorganic phosphate, total protein, total cholesterol and glucose) did not differ between the day and night trials. These data indicate that the untoward influence of furosemide on serum chloride might vary with its time of administration.

Administration, Oral↗

PubMed1990

Chronopharmacological study of furosemide; (VI). Influence of prolonged exposure to continuous light.

We have previously reported that a time-dependent variability is observed in the diuretic effects of furosemide in rats. The present study was undertaken to examine the influence of prolonged exposure to continuous light on chronopharmacological profiles of furosemide in Wistar rats. In study I, rats were maintained for more than 2 weeks under conditions of light (0700-1900 hrs) and dark (1900-0700 hrs) (L-D). Furosemide (30 mg/kg) was orally given at 1200 hrs or at 2400 hrs. Urine was collected for 8 hours after the drug and urinary excretion of sodium and furosemide were determined respectively. Thereafter, these rats were exposed to continuous light (L-L) for the next 4 weeks, and were again maintained under the L-D cycle. The identical trial of study I was repeated at the end of the L-L (study II) and the second L-D (study III) conditions. Urine volume and urinary excretion of sodium and furosemide following the drug were significantly greater at 1200 hrs than at 2400 hrs under conditions of L-D (study I and III). However these administration time-dependent changes in the effects of furosemide and its urinary amount disappeared with L-L condition (study II). These findings indicate that the mode of the time-dependent changes in the effects of furosemide is altered by prolonged exposure to continuous light.

Animals↗