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Biomedical subjects

A Ebihara

Publications and source records attributed to A Ebihara.

At least 91 records · Page 5Linked to original sources
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↗
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

[Statistical study of endodontically treated teeth by undergraduate students from 1979 to 1989].

In clinical education in dentistry, it is very important and significant that the undergraduate students themselves treat the patients. According to the rapid progress of dental science, the complexity and the high degree of the quality of education increase more and more, so that it is a requisite to make our efforts to enrich the quality of the practice at all times. In this paper, we investigated and statistically analyzed the result of 3,359 cases (test cases: 304, general cases: 3,055) which were treated endodontically by the undergraduate students of Tokyo Medical and Dental University in the four classes of 1979, 1982, 1986 and 1989. Both the number of the treated cases and the patients decreased year by year. Only the patients above sixty years old showed a tendency to increase in number. The result of the test cases was not always representative of the result of the general cases. If the clinical instructors for the undergraduate students grasp the detailed results of this study, we can expect that they can guide and train the undergraduate students more effectively.

Adult↗
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↗