Biomedical subjects

A Fujimura

Publications and source records attributed to A Fujimura.

At least 217 records · Page 12Linked to original sources

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 mechanism of polyethylene glycol-induced natriuresis in rats: role of atrial natriuretic hormone.

A putative role of atrial natriuretic hormone (ANH) in a polyethylene glycol (PEG) 200-induced natriuresis was examined in conscious Wistar rats. Low molecular weight PEG 200 (0.5 or 1.0 ml/100g body weight) was orally administered to rats by gavage. Urine was collected during a 3 hr test period and blood was obtained at the end of each experiment for measurement of ANH, PRA, clearance studies and for indirect indices of plasma volume. Urinary excretion of sodium and volume increased while plasma ANH concentrations were markedly decreased in a dose-related manner following PEG 200 administration. The osmotic clearance was also elevated following PEG 200 administration. No significant change was observed in any of the parameters following high molecular weight PEG 8000. The observed decrease in ANH was associated with an apparent contraction of plasma volume despite the increased serum osmolality. These data indicate that the ANH inhibitory influence of the decreased plasma volume takes precedence over the stimulatory effect of the hyperosmolality and the latter is primarily responsible for the increased osmotic clearance and natriuresis observed in this model.

Administration, Oral↗

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

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

Dose dependent effect of diltiazem on the pharmacokinetics of nifedipine.

The effect of diltiazem pretreatment on the pharmacokinetics of nifedipine were determined in six healthy male volunteers. Placebo or diltiazem (30 mg and 90 mg) was given orally three times daily for 3 days in a double-blind, Latin square method. On the fourth day, a 20-mg nifedipine was given orally 1 hour after the last dose of placebo or diltiazem. The mean elimination half-life of nifedipine prolonged significantly following diltiazem (2.54 hours on placebo vs 3.40 hours on 30 mg diltiazem and 3.47 on 90 mg diltiazem, both P less than .01). The mean AUC of nifedipine increased during diltiazem (1726.6 nmol X hr/ml on placebo vs 3838.0 on 30 mg diltiazem, and 5370.0 on 90 mg diltiazem, both P less than .05, 30 mg vs 90 mg, 0.1 less than P less than .05). The ratio of the AUC of primary metabolite (nitropyridine form) to the AUC of nifedipine was reduced by diltiazem pretreatment in a dose-dependent manner. ICG clearance was not influenced following diltiazem. These results indicate that diltiazem dose-dependently alters the pharmacokinetic profiles of nifedipine. The ICG clearance test showed that the liver blood flow did not decrease during diltiazem therapy, therefore, the reduction in the metabolic clearance of nifedipine might be caused by inhibiting effect of diltiazem on the activity of drug oxidizing enzymes.

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↗

PubMed1989

The influence of fever on the pharmacokinetics of pranoprofen in elderly subjects.

Pranoprofen (75 mg) was given orally during febrile (mean body temperature 38.3 degrees C) and afebrile (mean body temperature 36.3 degrees C) periods in nine elderly subjects. Blood samples for plasma drug concentrations were taken for a 10 hour post-drug period. The mean elimination half-life (t1/2 beta) was significantly prolonged and the mean area under the time-concentration curve from 0 to 10 hrs (AUC0-10) was greater, although not significantly, during fever. No significant difference was observed in the time to maximum concentration (tmax), maximum plasma concentration (Cmax) or apparent volume of distribution (Vd/F) between the both dosages. There was a positive correlation (r = 0.448, 0.05 less than P less than 0.10) between the body temperature and t1/2 beta of pranoprofen. These data indicate that the clearance of pranoprofen is reduced during fever in elderly subjects.

Aged↗

PubMed1989

Clinical pharmacology of dilevalol (I). Comparison of the pharmacokinetic and pharmacodynamic properties of dilevalol and labetalol after a single oral administration in healthy subjects.

Dilevalol (25 mg----50 mg----100 mg) or labetalol (100 mg) was given orally in six healthy subjects. The study was carried out on four occasions with a week interval. Blood samples for plasma drug concentrations were taken for a 24-hour post-drug period. Blood pressure (BP) as well as heart rate (HR) at supine position, during 50 degrees tilting and during a submaximal exercise were measured after each treatment. The mean maximum plasma concentration (Cmax) as well as the mean area under the plasma concentration-time curve (AUC) increased in a dose-dependent manner after dilevalol. These parameters after dilevalol 100 mg were significantly lower than after labetalol 100 mg. No significant differences were observed in the time to maximum concentration (tmax), the distribution half-life (t1/2 alpha) or the elimination half-life (t1/2 beta) between dilevalol and labetalol. There were no significant differences in BP at supine position or during 50 degrees tilting among the dosages. Postural changes in HR during 50 degrees tilting was significantly smaller after dilevalol 100 mg than following labetalol 100 mg. The suppressing effect of dilevalol 100 mg on an increase in HR during a submaximal exercise was significantly greater than during labetalol 100 mg. These data indicate that although plasma drug concentrations are lower after dilevalol than following labetalol, the beta-blocking activity of dilevalol is more potent than labetalol.

Administration, Oral↗

PubMed1989

Clinical pharmacology of dilevalol (II). The pharmacokinetic, pharmacodynamic, and tolerance studies of dilevalol during repeated administration in healthy subjects.

Dilevalol (50 mg) was given orally twice daily for eight days in six healthy subjects. All parameters were obtained following 1st (on day 1) and 15th (on day 8) dosages. Blood samples for plasma drug concentrations were taken for a 12-hour (after 1st dosage) or a 24-hour (after 15th dosage) post-drug period. Blood pressure (BP) as well as heart rate (HR) at supine position, during 50 degrees tilting and during a submaximal exercise were measured after each dosage. The mean time to maximum concentration (tmax) was faster, and the mean area under the plasma concentration-time curve (AUC) was greater after 15th dosage than following 1st dosage. No significant differences were observed in the maximum plasma concentration (Cmax), the distribution half-life (t 1/2 alpha) or the elimination half-life (t 1/2 beta) between the two dosages. BP at supine position as well as during 50 degrees tilting decreased significantly after each dosage, and did not differ between 1st and 15th dosages. Postural changes in BP or HR during 50 degrees tilting were not induced following 1st or 15th dosage. The suppressing effects (%R) on an increase in HR during a submaximal exercise were significantly larger after 15th dosage than after 1st dosage. A significant correlation was observed between plasma dilevalol concentration and %R in HR. These data indicate that the hypotensive effect of dilevalol is not altered during the repeated administration of the drug for 8 days. However, the beta-blocking activity of dilevalol might be enhanced during the repeated dosages, which is, in part, attributed to dosage-dependent elevation in plasma drug concentrations.

Administration, Oral↗

PubMed1989

Chronopharmacokinetic studies of pranoprofen and procainamide.

There is increasing evidence demonstrating that plasma drug concentrations are affected by their time of administration. In the current study, the chronopharmacokinetic profiles of an antipyretic agent, pranoprofen, and an antiarrhythmic agent, procainamide, were examined. In the first study, 75 mg of pranoprofen was given orally in seven healthy subjects at 10:00 (morning trial) or 22:00 (evening trial). In the second study, 500 mg of procainamide was given orally in eight subjects with premature ventricular contractions at 10:00 or 22:00. Blood samples for plasma drug concentrations were taken for a 10-hour (pranoprofen study) or a 24-hour (procainamide study) post-drug period. In the first (pranoprofen) study, the mean time to maximum concentration was significantly shorter, and the mean maximum plasma concentration as well as absorption rate constant had a tendency to be greater after the morning than after the evening trial. The mean area under the plasma concentration-time curve, elimination half-life or oral clearance of the morning and evening dosages did not differ. In the second (procainamide) study, no significant difference was observed in any pharmacokinetic parameter concerning procainamide or its active metabolite, N-acetyl-procainamide (NAPA) between the morning and evening trials. These data indicate that plasma levels of pranoprofen are affected by its administration time while plasma concentrations of procainamide and NAPA do not vary with the time of dosage.

Acecainide↗

PubMed1989

Chronopharmacological study of furosemide in rats: (III). Examination in spontaneously hypertensive and Wistar-Kyoto rats.

We have previously reported that a time-dependent variability is observed in the diuretic effect of furosemide in Wistar rats and the adrenergic system is involved in the mechanisms responsible for this phenomenon. The present study was undertaken to examine chronopharmacological profiles of furosemide in two related but different strains of Wistar rats, spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Furosemide (5 mg/kg) was administered intra-arterially in SHR and WKY 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. In both groups of rats, urine volume and urinary excretion of sodium and furosemide were significantly greater at 1000 hrs (03HALO) than at 2200 hrs (15HALO) as observed in the previous study using Wistar rats. The diuretic effects of furosemide in SHR was not different from those in WKY at 1000 hrs (03HALO) or at 2200 hrs (15HALO). These data indicate that the effects of furosemide also vary with a time of administration in SHR and WKY as observed in Wistar rats. In addition, the present study suggest that the mode of the time-dependent changes in the effects of furosemide in SHR, which is reported to have an altered circadian rhythm in the adrenergic system, does not differ from that in WKY rat.

Animals↗

PubMed1989

Calcium infusion increases plasma atrial natriuretic factor in spontaneously hypertensive rats.

The effect of calcium on plasma atrial natriuretic factor (ANF) concentration was determined in spontaneously hypertensive rats (SHR) and their control, Wistar-Kyoto (WKY) rats. CaCl2 10.5 mg (0.095 mmol) in 0.54 ml 5% glucose or an equal volume of vehicle alone was infused intravenously for 30 minutes into conscious precannulated SHR (vehicle, n = 16; CaCl2, n = 16) and WKY rats (vehicle, n = 25; CaCl2, n = 15). Direct systolic blood pressure was measured throughout the infusion period. Blood samples for serum total calcium and plasma ANF were obtained at the end of each experiment. The systolic blood pressure did not change significantly during infusion of the vehicle or CaCl2 in either strain. No significant difference was observed in serum total calcium concentration between SHR and WKY rats after vehicle (9.8 +/- 0.1 [mean +/- SEM] mg/dl vs. 10.0 +/- 0.1) or after CaCl2 infusion (12.2 +/- 0.3 vs. 12.2 +/- 0.2). Plasma ANF concentrations after both vehicle and CaCl2 infusion were significantly higher in SHR than in WKY rats (vehicle, 211 +/- 24 pg/ml vs. 129 +/- 11, p less than 0.05; CaCl2, 395 +/- 21 vs. 278 +/- 33, p less than 0.05). There were high degrees of correlation between serum total calcium and plasma ANF both in SHR (r = 0.77, p less than 0.001) and in WKY rats (r = 0.76, p less than 0.001). No significant difference was observed in the slopes of the regression lines of ANF as a function of the serum total calcium concentration between SHR and WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Infusion of atrial natriuretic hormone in DOCA/salt and spontaneously hypertensive rats.

The effects of a 6-day infusion of atrial natriuretic hormone (ANH) on blood pressure and urinary sodium excretion were determined in conscious DOCA/salt and spontaneously hypertensive rats. The DOCA/salt rats were randomly divided into two groups after 4 weeks and either infused by osmotic minipump with 32.5 pmol/h of ANH in 0.1% gelatin vehicle or sham operated with emplacement of a blind cannula. Thirteen-week-old spontaneously hypertensive rats were studied in a similar fashion. The baseline systolic blood pressure prior to the infusion was 176 +/- 7 mmHg (x +/- SEM) in the ANH group and 169 +/- 5 mmHg in the sham group of DOCA/salt animals. The ANH infusion in the DOCA/salt animals dropped their blood pressure to 160 +/- 10 mmHg (p less than 0.01) compared to that in the sham controls which continued to rise to 200 +/- 7 mmHg. The blood pressure response to ANH infusion in the spontaneously hypertensive rats was slightly greater, with a blood pressure of 192 +/- 5 mmHg in the sham group and 132 +/- 3 mmHg in the ANH-infused animals. ANH infusion produces a qualitatively similar blood pressure response in the DOCA/salt rat as well as the other hypertensive models. This response is relatively less on a quantitative basis than that observed in the spontaneously hypertensive rats and is not related to changes in sodium balance or volume contraction.

Animals↗