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Biomedical subjects

A Ebihara

Publications and source records attributed to A Ebihara.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1990

Chronopharmacological study of furosemide; (IV). Examination in aged rats.

We have previously reported that a time-dependent variability is observed in the diuretic effects of furosemide in young Wistar rats. The present study was undertaken to examine the influence of ageing on chronopharmacological profiles of furosemide in rats. Furosemide (5 mg/kg) was injected intra-arterially in young (10-11 week old) and aged (21-22 month old) Wistar rats at 1000 hrs or at 2200 hrs. 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 following the drug injection were significantly greater at 1000 hrs than at 2200 hrs in the young rats as observed in the previous study. However these administration time-dependent changes in the effects of furosemide and its urinary amount disappeared in the aged rats. These findings indicate that the mode of the time-dependent changes in the effects of furosemide is altered in aged Wistar rats.

Aging↗
PubMed1990

The influence of delivery mode on biological inactive renin level in umbilical cord blood.

In order to investigate the influence of delivery mode on biological inactive renin levels in fetal circulation, plasma inactive renin (PIR), plasma renin activity (PRA) and plasma total renin (PTR) were measured in umbilical venous blood samples of 21 infants delivered vaginally after spontaneous labor and of 9 infants delivered by elective cesarean section after the onset of labor. Biological renin activities were measured by bioassay. The PIR levels in infants delivered vaginally were significantly lower than those in infants delivered by cesarean section, while the PRA levels were the opposite. However, the PTR levels were not significantly different between the two groups. These results suggest that the plasma levels of biological inactive renin in infants delivered vaginally may decrease, probably due to its conversion to active renin in the second stage of labor.

Adult↗
PubMed1990

Effects of diltiazem on the pharmacokinetics of nifedipine.

To evaluate the effect of diltiazem pretreatment (60 mg three times a day for 3 days) on pharmacokinetics and pharmacodynamic effect of nifedipine, six healthy subjects received 20 mg nifedipine orally on two occasions using a double-blind cross-over, placebo-controlled method. Diltiazem induced a marked increment of the area under the plasma concentration-time curve (AUC) for nifedipine by a mean of 140% and reduced the total body clearance (Cl) from 0.0043 +/- 0.0019 to 0.0017 +/- 0.0006 ml/min/kg (p less than 0.05, mean +/- SD). The biological half-life (t1/2) of nifedipine was prolonged from 2.46 +/- 0.65 to 3.21 +/- 0.92 h (p less than 0.05) without any changes in indocyanine green (ICG) clearance. Diltiazem did not produce significant changes of AUC, Cl, and t1/2 for the acid metabolite of nifedipine. Blood pressure (BP) after nifedipine administration with diltiazem pretreatment was more decreased than that without diltiazem. Both a decreased hepatic clearance and an increased bio-availability of nifedipine by diltiazem probably explain the significant changes in pharmacokinetics and hemodynamics of nifedipine. A clinically important drug interaction may occur with nifedipine when diltiazem is administered concurrently.

Adult↗
PubMed1990

Daily variation in influence of lithium on serum calcium concentration: a preliminary report.

1. One millilitre of 5% glucose (vehicle, n = 10) or 1 mL solution of lithium chloride (LiCl) (0.5 or 2.0 mmol/kg per day, n = 10 for each) was injected intraperitoneally in Wistar rats at 10:00 or 22:00 h for 6 days. Blood samples for ionized and total calcium were taken on day 7. 2. Mild elevations in ionized, but not non-ionized (total-ionized) calcium were observed following LiCl treatment in both administration times. 3. The increment in ionized calcium was greater when LiCl was injected at 22:00 h than when it was given at 10:00 h. 4. These data indicate that: (1) the influence of lithium on calcium metabolism varies with its administration time; and (2) mild hypercalcaemia induced by the agent mainly depends on the elevation in the ionized fraction of calcium.

Animals↗
PubMed1990

Circadian rhythm in recognition threshold of salt taste in healthy subjects.

The circadian rhythm in recognition threshold of salt taste was examined in six healthy young subjects. Plasma aldosterone (PA) and cortisol concentrations, plasma renin activity (PRA), salivary sodium concentration, and salt recognition thresholds were measured every 3 h for a 24-h period. The salt recognition threshold and salivary sodium concentration exhibited similar circadian rhythms, with the lowest values recorded in the afternoon. Positive correlations were observed between the recognition threshold and salivary sodium (P less than 0.001) and between cortisol and PA (P less than 0.001). There was no correlation between PRA and PA. A negative correlation was observed between PA and salivary sodium concentration (P less than 0.01). These data indicate that the recognition threshold for salt taste has a circadian rhythm in young healthy subjects. This rhythm appears to be related to daily variations in the plasma aldosterone concentration and its subsequent effects on salivary sodium concentration.

Adult↗
PubMed1989

Chronopharmacological study of nitrendipine in healthy subjects.

Nitrendipine 20 mg or placebo was given orally to eight healthy subjects in a cross-over design separated by 1 or 2 weeks. Drug was given at 9:00 AM (morning dosage) or at 9:00 PM (evening dosage). Systolic and diastolic blood pressure (SBP, DBP) were measured just before and 1, 2, 3, 4, 5, 7, 9, 12 and 24 hrs after treatment. Plasma nitrendipine concentrations were determined at 0.5, 1, 2, 3, 4, 5, 7, 9, 12 and 24 hrs and plasma catecholamines were measured at 2 and 5 hrs following drug administration. SBP did not decrease significantly after nitrendipine compared to after placebo at 9:00 AM or at 9:00 PM. DBP decreased significantly at 2, 3, 4 and 5 hrs after nitrendipine at 9:00 AM, but only at 4 hours after the 9:00 PM dose. Mean plasma nitrendipine concentrations during the absorption phase were lower after the evening dosage compared to the morning interval. Maximum plasma concentration (Cmax) was significantly lower and time to maximum concentration (tmax) tended to be longer after the evening dosage. Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) and half-life of the terminal elimination phase (t1/2 beta) of the morning and evening dosages did not differ. A significant correlation was observed between plasma nitrendipine concentrations and changes in DBP during the drug treatment. Plasma noradrenaline concentrations were significantly higher 5 hours after nitrendipine compared to after placebo at 9:00 AM, but not at 9:00 PM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Clinical pharmacology of dilevalol (III). A pharmacokinetic study of dilevalol in elderly subjects with essential hypertension.

Dilevalol (100 mg) was given once daily for 8 days in eight elderly subjects with essential hypertension. Blood samples for plasma dilevalol concentrations were taken during an 8-hour post-drug period following the first and eighth dosages, and the time to maximum concentration (tmax), maximum plasma concentration (Cmax), distribution half-life (t1/2 alpha), elimination half-life (t1/2 beta) and area under the plasma concentration-time curve (AUC) were determined. A wide intra-subject variability was observed in tmax during the repeated administration. A high inter-subject variability was also demonstrated in tmax, Cmax, t1/2 beta and AUC during both observation periods. No significant difference was observed, however, in these pharmacokinetic parameters between the first and eighth dosages. These data indicate that the pharmacokinetic profiles of dilevalol are not altered during 8 days of therapy in elderly subjects with essential hypertension. Since elderly subjects are potentially heterogenous in capacities for handling the drug, the observed variability in pharmacokinetic parameters may reflect the heterogeneity in the sample chosen for examination in the current study.

Adrenergic beta-Antagonists↗
PubMed1989

Effects of H2-receptor antagonists on plasma aldosterone response to angiotensin II in healthy subjects; (II). Comparison of cimetidine and ranitidine.

The effects of H2-receptor antagonists, cimetidine and ranitidine, on plasma aldosterone response to angiotensin II (AII) were examined in six healthy subjects. The study was carried out on three different occasions with a two week interval. Cimetidine (400 mg), ranitidine (150 mg) or a placebo was given orally every 12 hours for 3 days in a double-blind, cross-over, double-dummy design. On the fourth day, 1 hour after the final (seventh) administration of the same agent, furosemide (20 mg) was injected intravenously. The plasma levels of renin activity (PRA), AII and aldosterone (PA) were determined for a 120 minute period after furosemide. PRA, AII and PA increased after furosemide with as well as without H2-receptor antagonist. The basal and stimulated levels of these parameters were not significantly different at any observation point among the three regimen groups. A significant correlation was observed between AII and PA with placebo (P less than 0.01) and ranitidine (P less than 0.01), but not with cimetidine (P greater than 0.05). The slope of the regression line with ranitidine was not significantly different from that of the placebo. These data indicate that the PA response to AII is blunted by cimetidine, but not by ranitidine. The current study supports the idea that this blunted response during cimetidine is independent of the blockade of H2-receptor.

Administration, Oral↗
PubMed1989

Influence of indomethacin on a reduction in forearm blood flow induced by propranolol in healthy subjects.

The influence of indomethacin on a reduction in forearm blood flow (FBF) induced by propranolol was investigated in eight healthy subjects. Indomethacin was orally administered (75 mg daily for 3 days) in a randomized cross-over design. Blood pressure (BP) was slightly decreased after a single oral administration of propranolol (40 mg) alone. However BP was slightly increased after the drug with indomethacin pretreatment. FBF was significantly decreased after propranolol with or without indomethacin. No significant difference was observed in FBF before or after propranolol between both groups. Plasma renin activity (PRA) was reduced by indomethacin pretreatment. These results suggest that the reduction in FBF induced by propranolol is not augmented with indomethacin.

Adult↗
PubMed1989

Effects of traxanox sodium on blood pressure and serum uric acid in hypertensive patients: a preliminary study.

The effects of chronic administration of traxanox sodium (traxanox) on blood pressure and serum uric acid level were investigated in 15 patients who had mild to moderate hypertension. Traxanox or its placebo was orally administered in a single-blind protocol. Blood pressure was significantly reduced from baseline after treatment with traxanox. The serum uric acid level after drug administration was significantly lower than with placebo whereas urinary uric acid excretion was significantly greater and uric acid clearance tended to be greater. These results indicate that chronic administration of traxanox reduces serum uric acid level as well as blood pressure in patients with mild to moderate hypertension. This reduction in serum uric acid is due in part to a traxanox-induced elevation of urinary uric acid excretion.

Adult↗