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Biomedical subjects

A Ebihara

Publications and source records attributed to A Ebihara.

At least 127 records · Page 7Linked to original sources
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

Effect of diltiazem on the pharmacokinetics of propranolol, metoprolol and atenolol.

The pharmacokinetic interaction between diltiazem and three beta-adrenoceptor blockers propranolol, metoprolol and atenolol was investigated in healthy volunteers given diltiazem 30 mg or placebo t.d.s. for 3 days, followed by a single dose of propranolol 20 mg, metoprolol 40 mg or atenolol 50 mg. The AUCs of propranolol and metoprolol were significantly increased after diltiazem and it significantly prolonged the elimination half-life of metoprolol. In contrast, it did not significantly affect the pharmacokinetics of atenolol. Propranolol significantly decreased the resting pulse rate after diltiazem pretreatment as compared to placebo. The results indicate that diltiazem impaired the clearance of propranolol and metoprolol, which are principally metabolized by an oxidative pathway, and that the kinetic interaction between diltiazem and propranolol may partly be related to the significant reduction in the pulse rate produced by the latter.

Adult↗
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

Effects on autonomic function of a new angiotensin converting enzyme inhibitor, ramipril.

To investigate the effects of ramipril, a new angiotensin converting enzyme inhibitor, on autonomic function, autonomic function tests were performed in eight healthy male subjects, aged 22-26 years, after single oral administration of 5 mg of ramipril or placebo, in a randomized, double-blind, crossover design. Measurements of heart rate variability and diving reflex test were performed as indices of parasympathetic tone. Forearm isometric exercise (handgrip test) and cold pressor test were carried out to evaluate sympathetic nervous reactivity. Supine systolic blood pressure was decreased significantly after ramipril (F = 11.16, p less than 0.01), but diastolic blood pressure was not. Heart rate at rest did not significantly differ between ramipril and placebo. Heart rate variability was significantly increased 120 min after ramipril [5.5 +/- 0.7% (SEM) on ramipril and 3.7 +/- 0.2% on placebo; F = 7.13, p less than 0.05]. However, reflex bradycardia during the diving test was not enhanced after ramipril. Plasma norepinephrine concentrations before and after handgrip test were not influenced by ramipril. Increments of mean blood pressure and heart rate during handgrip or cold pressor test did not significantly differ between ramipril and placebo, either. These results suggest that ramipril may enhance cardiac vagal tone without affecting sympathetic nervous activity. Enhanced parasympathetic activity could be related to an absence of reflex tachycardia following the administration of ramipril.

Adult↗
PubMed1989

Chronopharmacological study of bunazosin hydrochloride in healthy subjects.

Bunazosin, an alpha-1 adrenoreceptor blocking agent, was given orally to six healthy subjects in the morning or in the evening in order to examine the time-dependent variations in the pharmacological effects of the drug. The study was carried out on four occasions in a placebo controlled cross-over design. No significant change was observed in blood pressure either after the morning or the evening dosage. Finger skin blood flow (FSBF) assessed by laser Doppler flowmetry increased significantly after the morning dosage, but not after the evening trial. The plasma concentration of bunazosin in the morning in general had a tendency to be greater than that in the evening. A significant correlation was observed between the plasma concentrations and the increments in the FSBF. These results indicate that the pharmacological effects of bunazosin are greater following morning dosage. The present study supports the concept that the time-dependent differences in the effect of bunazosin are, at least, caused by the time-dependent changes in plasma drug concentration.

Adrenergic alpha-Antagonists↗
PubMed1989

Dosage regimen of ranitidine in patients with renal impairment.

The validity of the Giusti-Hayton method for dosage regimen adjustment in patients with renal impairment was investigated using ranitidine. Five normal healthy volunteers received a single ranitidine recommended dose of 150 mg, and 20 patients with renal disease received single administration in doses individually calculated by the Giusti-Hayton method from each patient's creatinine clearance level, and the various pharmacokinetic parameters were compared. As a result, the area under the time-concentration curve 0----infinity (AUC0----infinity) in the renal disease patients was almost comparable to that in the normal healthy volunteers. The Giusti-Hayton method was considered useful to keep both the AUC0----infinity constant and the mean blood level of the drug in a steady state, in any degree of renal impairment.

Administration, Oral↗
PubMed1988

Chronopharmacological study of furosemide in rats: (II). Influence of beta-adrenoceptor blockade.

We have previously demonstrated a time-dependent variability in the diuretic effect of furosemide in rats. The present study was undertaken to evaluate the influence of beta-adrenoceptor blockade on these time-dependent variations. Furosemide (5 mg/kg) was administered intra-arterially in Wistar rats at 1000 hrs (03HALO) or at 2200 hrs (15HALO) with pretreatment with either propranolol (10 mg/kg) or atenolol (10 mg/kg). Urine was collected for 60 min after furosemide administration and urinary excretion of sodium and furosemide were determined respectively. Propranolol pretreatment abolished the temporal variations observed in urine volume, urinary sodium and furosemide levels during the observation periods. With atenolol pretreatment, however, all these variables were significantly greater at 1000 hrs (03HALO) than at 2200 hrs (15HALO) as observed in the previous study. These results suggest that the beta-adrenoceptor-mediated stimuli, which is blocked by propranolol but not by atenolol, is responsible for the time-dependent changes in the diuretic effect of furosemide.

Animals↗
PubMed1988

Role of angiotensin II in renal prostaglandin E2 production after furosemide administration.

The role of plasma angiotensin II (Ang II) in furosemide-stimulated renal prostaglandin E2 (PGE2) production was evaluated in eight healthy subjects. Urine was collected for 60 minutes after furosemide administration (20 mg i.v.) with or without captopril pretreatment, and urinary excretion of PGE2, sodium, and furosemide was determined. Plasma renin activity (PRA) and Ang II were also measured before and 60 minutes after furosemide administration. Urinary PGE2 excretion, PRA, and Ang II increased after furosemide administration without captopril pretreatment, and there was a significant correlation between the increment in Ang II and that in urinary PGE2 excretion. Urinary PGE2 excretion and Ang II did not increase after furosemide administration with captopril pretreatment. Urine volume and urinary excretion of sodium and furosemide were not influenced by captopril pretreatment. These results suggest that Ang II may play an important role in furosemide-stimulated PGE2 production.

Adult↗
PubMed1988

Chronopharmacological study of furosemide in human subjects.

The present study was undertaken to determine whether the diuretic effects of furosemide depend on the administration time or not. After furosemide 20 mg or a placebo was administered intravenously in 12 human subjects at 09h00 or at 21h00, urine volume and urinary excretion of sodium, chloride and furosemide were determined for 3 h. There were no significant differences in the amount of urine, or of urinary excretion of sodium and chloride between when a placebo was given at 09h00 and when it was given at 21h00. When furosemide was administered at 21h00, the urine volume and urinary excretion of sodium, chloride and furosemide during the first 60 min were significantly greater than those, when the drug was administered at 09h00. There was a marked correlation between the urinary output of furosmeide and the urine volume, urinary sodium and urinary chloride. These results suggest that the diuretic effects of furosemide vary with the time of administration and the observed variations are mainly dependent on the amount of furosemide secreted into urine.

Adult↗
PubMed1987

The effect of propranolol on urinary prostaglandin E2 after frusemide administration in healthy subjects.

We have evaluated the effect of propranolol on urinary prostaglandin E2 (PGE2) excretion after frusemide administration in 8 healthy subjects. Urine was collected for 60 min after frusemide administration (20 mg intravenously) with or without propranolol pretreatment, and urinary excretion of PGE2, frusemide, and sodium were determined. Plasma renin activity (PRA) was also measured before and 60 min after frusemide administration. Urinary PGE2 excretion after frusemide administration and frusemide-stimulated PRA were reduced after propranolol pretreatment. However, urine volume and the urinary excretion of frusemide and sodium were not influenced by propranolol pretreatment. These results suggest that urinary PGE2 excretion after frusemide administration may be reduced by propranolol and that the mechanism responsible for the effect of propranolol on the frusemide-induced renal PGE2 production may be, at least in part, secondary to inhibition of the renin-angiotensin system.

Adult↗
PubMed1987

Chronotoxicity of beta-adrenoceptor blocking agent in spontaneously hypertensive rats.

1. Chronotoxicity of a single LD50 dosage of beta-adrenoceptor blocking agent, pindolol, was determined in spontaneously hypertensive rats (SHR) and Wistar-Kyoto control rats (WKY). 2. The 24 h mortality was greater when pindolol was administered at 00.00 h than when it was administered at 12.00 h in both SHR and WKY. 3. The chronogram of the mortality in SHR was similar to that in WKY. 4. These results indicate that the mode of circadian variation in the acute toxicity of pindolol in SHR is not different from that in WKY.

Adrenergic beta-Antagonists↗
PubMed1987

The paradoxical adverse effect of verapamil for treating clinical paroxysmal supraventricular tachycardia.

The intravenous administration of verapamil to 2 patients with paroxysmal supraventricular tachycardia (PSVT) resulted in an induction of PSVT during a programmed electrophysiological stimulation study. Each patient had a documented episode of PSVT. Baseline programmed stimulation studies revealed neither induction of PSVT nor an atrial echo; however, PSVT was induced immediately after injecting verapamil (0.15 mg/kg) intravenously in both patients. In 1 patient, the study was repeated 2 days later and similar results were obtained. The serum concentration of verapamil when PSVT was induced was about 80 ng/ml in both cases. Clinicians using verapamil should note that this antiarrhythmic drug may aggravate PSVT, depending on critical changes in AV nodal conduction and refractoriness.

Adult↗