Biomedical subjects

A Fujimura

Publications and source records attributed to A Fujimura.

At least 73 records · Page 4Linked to original sources

PubMed1995

Studies on the development of the articular part of the temporal bone with special reference to the postglenoid process.

The development and significance of the postglenoid process on the articular surface of the temporal bone were studied using 217 Indian skulls, which were divided by their level of tooth eruption into 6 developmental stages; preeruption period (Stage I), initial stage (m1 eruption) of the deciduous dentition period (Stage II), middle stage (m2 eruption) of the deciduous dentition period (Stage III), late state (eruption of 20 deciduous teeth) of the deciduous dentition period (Stage IV), mixed dentition period (Stage V), and permanent dentition period (Stage VI). Each skull was mounted on a Kraniophor in such a way that the auriculoorbital (Frankfurt) plane was positioned vertical to the horizontal plane and photographed at a focal distance of 40 cm. Using the Frankfurt plane as a base line, the vertical distances to the lowest point of the postglenoid process (a-A), to the deepest point of the mandibular fossa (b-B), and to the mid-point of the articular tubercle (c-C) were measured. The distances from various points of the mandibular fossa to the articular surface of the temporal bone were measured at the level of the Frankfurt plane. The results may be summarized as follows: The length of the postglenoid process as measured from the Frankfurt plane was 0.58 mm at Stage I and 0.75 mm at Stage II. It increased by 0.6-1.0 mm at each developmental stage. By Stage VI, it had increased to 3.85 mm (six- to seven-fold increase from the initial value). The anteroposterior width of the postglenoid process remained almost unchanged throughout the developmental stages. The growth of the articular structures of the temporal bone from the preeruption to deciduous dentition period increased 73% in the total anteroposterior dimension (5.22 mm) and 44% in the total vertical dimension (3.32 mm). The vertical dimension of the mandibular fossa began to rapidly increase following the eruption of the deciduous first molars.

Adolescent↗

PubMed1995

Influence of aging on the oxidative and conjugative metabolism of propranolol.

The influence of aging on the hepatic metabolism of propranolol, i.e. conjugation, side-chain oxidation and ring oxidation, was investigated in 32 in-patients aged 30 to 84 yrs. Plasma propranolol concentration and main urinary metabolites [propranolol glucuronide (PPLG), naphthoxylactic acid (NLA), and 4-hydroxypropranolol (40HP)] were determined after a single oral dose of 20 mg propranolol. There were significant correlations between age and 1) maximum propranolol concentration, 2) area under the plasma concentration-time curve, and 3) elimination half-life. The apparent oral clearance of propranolol was inversely correlated with age. Partial metabolic clearance (PMC) to 40HP (ring oxidation) and PMC to NLA (side-chain oxidation) were significantly correlated with age, while PMC to PPLG was not. These observations suggest that there are age-related reductions in two oxidizing capacities, while there is no significant influence of aging on the conjugating capacity. The age-related reduction in oral clearance of propranolol may be mainly caused by the decline in the capacity of two different oxidation pathways.

Adrenergic beta-Antagonists↗

PubMed1994

Comparison of the pharmacokinetics, pharmacodynamics, and safety of oral (Catapres) and transdermal (M-5041T) clonidine in healthy subjects.

The pharmacokinetic as well as pharmacodynamic properties of a transdermal clonidine, M-5041T (M) and its safety were compared with those of oral clonidine, Catapres (Nippon Boehringer Ingelheim, Hyogo, Japan). One patch of M containing 6 mg of clonidine was applied on the right chest for 3 days or one tablet of Catapres (.075 mg) was given orally every 12 hours for 3 days in eight healthy subjects. The study was conducted by a crossover design with 14 to 16 days' interval between the cross-over. Blood and urine samples for clonidine concentration were obtained, and blood pressure (BP) was measured for a 168-hour period after application of M and for a 96-hour period after initiation of Catapres therapy. Plasma concentration of clonidine increased gradually after application of M and decreased gradually after removal, whereas this parameter increased rapidly during the absorption phase and decreased rapidly in the elimination phase after each dosage of Catapres. Elimination half-life of clonidine after removal of M was significantly greater than that after the final dosage of Catapres. No significant difference was observed in maximum plasma concentration or area under the plasma concentration-time curve between the two trials. The BP lowering effects of M and Catapres did not differ significantly. Adverse symptoms occurred more frequently during Catapres therapy than during treatment with M. Most of these symptoms were observed when plasma clonidine concentration was relatively higher in each trial. These results suggest that M is effective for the treatment of hypertension with a lower incidence of adverse symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

PubMed1994

Renal clearance of lomefloxacin is decreased by furosemide.

The interaction between lomefloxacin, a new quinolone, and furosemide, a loop diuretic, has been examined. Oral lomefloxacin 200 mg and furosemide 40 mg were given together or separately to 8 healthy subjects, and blood and urine samples were obtained over the following 12 h. The plasma concentrations of lomefloxacin following coadministration with furosemide were higher than after lomefloxacin alone and its AUC was increased, and its total and renal clearances were decreased. No change in the pharmacokinetics of furosemide was found after coadministration of lomefloxacin. As quinolones and furosemide are reported to be excreted in urine by the renal tubular anion transport system, the present results suggest that the renal tubular secretion of lomefloxacin is diminished by furosemide. It is not clear whether this pharmacokinetic interaction might be clinically important.

Adult↗

PubMed1994

Time-dependent change in the toxic effects of amikacin on renal functions.

The present study was undertaken to examine whether there was a time-dependent change in the toxic effects of amikacin, an aminoglycoside, on renal functions. Male Wistar rats were maintained under conditions of light from 7 am to 7 pm and dark from 7 pm to 7 am. Amikacin (1.2 g/kg) was injected intraperitoneally to animals at 4 am, 10 am, 4 pm or 10 pm. Glomerular function estimated by creatinine clearance (Clcr) and tubular function estimated by urinary excretion of a loop diuretic, furosemide, which was excreted in urine mainly by tubular secretion, were determined before and 24 hours after amikacin injection. The values of these parameters were reduced by amikacin at each observation point. The magnitude of these decrements was greatest at 4 pm both for Clcr and urinary furosemide excretion. These results suggest that the toxic effects of amikacin on renal glomerular and tubular functions vary with its time of administration.

Amikacin↗

PubMed1994

Daily variation in the urinary excretion of furosemide in young and aged rats.

We have recently demonstrated that the time-dependent difference in urinary excretion of furosemide, a loop diuretic, diminishes during the aging process and disappears by 18 months of age in rats. The present study was undertaken to examine whether the amplitude of the daily variations in the urinary excretion of furosemide or their pattern, or both, are influenced in aged animals. Young (3 months of age) and aged (30 months of age) Wistar rats were maintained under conditions of light from 7 am to 7 pm and dark from 7 pm to 7 am. Furosemide (30 mg/kg) was given orally at 4 am, 8 am, 12 am, 4 pm, 8 pm or 12 pm. Urine was collected for 8 hours after furosemide administration and urinary excretion of furosemide was determined. There were significant daily variations in the urinary furosemide and the urine volume with the peak at 8 am and the trough at 12 pm in both groups of rats. The differences in these parameters between the 8 am and 12 pm trials were significantly smaller in the aged than in the young rats. These results suggest that the age-related alteration in the time-dependent phenomenon of furosemide is caused by the decreased amplitude of the daily variation in the urinary furosemide excretion and its diuretic effect.

Age Factors↗

PubMed1994

Effect of angiotensin II type 1 receptor antagonist on urinary prostaglandin E2 excretion following furosemide in rats.

The present study was undertaken to examine an effect of an angiotensin II type 1 (AT1) receptor antagonist on urinary prostaglandin E2 (PGE2) excretion following furosemide, a loop diuretic, in rats. Furosemide (30 mg/kg) was given orally with or without pretreatment with derapril (30 mg/kg), an angiotensin converting enzyme inhibitor, TCV-116 (1 mg/kg), an AT1 receptor antagonist, or losartan (10 mg/kg), another AT1 receptor antagonist. The 6-hour urine was collected following furosemide, and the urinary excretion of PGE2 was determined. The urinary PGE2 increased significantly following furosemide alone. However, such a furosemide-induced increase was not observed with pretreatment with derapril, TCV-116 or losartan. These results suggest that the increased urinary excretion of PGE2 following furosemide is blunted by derapril, TCV-116 and losartan. As TCV-116 and losartan are selective AT1 receptor antagonists, the effect of furosemide on renal PGE2 production, as reflected by the urinary PGE2, might be mediated by an activation of AT1 receptors.

Angiotensin II↗

PubMed1994

Administration time-dependent change in the effect of spironolactone in aged rats.

We have previously demonstrated that the natriuretic effect of spironolactone, a competitive antagonist of mineralocorticoid, varies with its administration time in young rats. The present study was undertaken to examine the influence of aging on chronopharmacological profiles of the agent. Spironolactone (10 and 50 mg/kg) was given orally at 12 am or 12 pm in young (12 weeks old) and aged (28 months old) Wistar rats. The 8-hour urine was collected after each administration, and the urinary sodium excretion was determined. The urinary sodium excretion increased dose-dependently following spironolactone in the young and aged groups of rats. The increments in this parameter in the 12 pm trial were significantly greater than those of the 12 am trial in the young rats. However, such an administration time-dependent difference in the effect of spironolactone was diminished and did not reach statistical significance in the aged animals. These results suggest that the mode of the administration time-dependent change in the effect of spironolactone is altered with age.

Aging↗

PubMed1994

Administration time-dependent toxicity of a new immunosuppressive agent, tacrolimus (FK 506).

We have previously shown that blood concentrations of tacrolimus, a new immunosuppressive agent, were greater when it was administered orally at 10 pm than when it was administered at 10 am in rats. The present study was undertaken to examine whether the toxic effects of tacrolimus show administration time-dependent variations. Male Wistar rats were maintained under conditions of light from 7 am to 7 pm and dark from 7 pm to 7 am. Tacrolimus (1 and 4 mg/kg) was given orally at 10 am (day trial) or 10 pm (night trial) for 14 days. Blood samples were obtained at 24 hours after the final dosage of the agent. Weight gain was smaller in the night trial than in the day trial. Plasma concentrations of urea and creatinine increased significantly in the night trial while the elevations in these parameters were not observed in the day trial. These results suggest that the toxic effects of tacrolimus also vary with its time of oral dosage.

Animals↗

PubMed1994

Administration time-dependent change in the effect of spironolactone in rats.

The present study was undertaken to examine whether the natriuretic effect of spironolactone, a competitive antagonist of mineralocorticoid, varies with its time of administration. Wistar rat maintained under the condition of light from 7 hr to 19 hr were divided into two groups. The first group had a bilateral adrenalectomy and received a 50-mg deoxycorticosterone acetate (DOCA) tablet intraperitoneally (DOCA group). The second group had a sham operation (control group). Spironolactone (50 mg/kg) was given orally at 12 hr or 24 hr, and the 8-hr urine was collected. At the end of the experiment, the blood sample for measurement of aldosterone was obtained at 12 hr and 24 hr in the control group. The natriuretic effect of spironolactone in the 24 hr-trial was significantly greater than that of the 12 hr-trial in the control group. However, such a time-dependent difference was diminished and did not reach statistical significance in the DOCA group. The plasma aldosterone concentration at 24 hr was significantly higher than that at 12 hr in the control group. These results suggest that the natriuretic effect of spironolactone varies with its time of administration. Daily variation in mineralocorticoid activity might be involved in this chronopharmacological phenomenon of spironolactone.

Administration, Oral↗

PubMed1994

Decrease in the time-dependent difference in urinary excretion of furosemide with age.

The influence of age on the time-dependent difference in urinary excretion of furosemide, a loop diuretic agent, was examined in this longitudinal study. Male Wistar rats were maintained under conditions of light from 07:00 to 19:00 h and dark from 19:00 to 07:00 h. Furosemide (30 mg/kg) was given orally at 12:00 h (day trial) or 00:00 h (night trial) to rats at 3 months of age, and urine was collected for 8 h after dosage. Thereafter, the identical protocol was repeated using the same animals at 6, 9, 12, 15, 18, and 21 months of age. The urinary excretion of furosemide was significantly greater in the day than in the night trial at 3 months of age. Such a time-dependent difference was observed for up to 15 months, but disappeared at 18 and 21 months of age. The time-dependent difference in urinary excretion of furosemide (day trial - night trial) decreased gradually throughout the observation period of the study. These results suggest that the time-dependent difference in the urinary excretion of furosemide diminishes during the aging process and disappears by 18 months of age in male Wistar rats.

Administration, Oral↗

PubMed1993

Influence of application site of a new transdermal clonidine, M-5041T, on its pharmacokinetics and pharmacodynamics in healthy subjects.

Influence of application site of a new transdermal clonidine, M-5041T(M), on its pharmacokinetics and pharmacodynamics were evaluated in eight human subjects. One patch of M-6 mg was applied for 3 days on the right chest (first trial), on the left arm (second trial), and on the upper abdomen (third trial). Blood samples for clonidine concentration were taken, and blood pressure (BP) was measured for a 120-hour postapplication period. Plasma concentrations of clonidine increased after application of M in each trial. This parameter in the second trial was significantly greater than that of the first and third trials. The values of maximum plasma concentration and area under the plasma concentration-time curve in the second trial were greater than those of other trials, but the differences did not reach significance. The BP-lowering effect of M in the second trial was significantly greater than that of the third trial. These results suggest that the plasma concentrations of clonidine after application of M and its hypotensive effect are affected by the site of application in human subjects.

Abdomen↗

PubMed1993

Pharmacokinetics and pharmacodynamics of a new transdermal clonidine, M-5041T, in healthy subjects.

The pharmacokinetic as well as the pharmacodynamic properties of a new transdermal clonidine, M-5041T (M), and its safety were evaluated after single and repeated applications. In the single-application study, one patch of M (4 mg-->6 mg-->8 mg) was applied for 3 days in eight healthy subjects. In the repeated-application study, first (0-72 hours), second (72-144 hours), and third (144-216 hours) patches of M 6 mg were applied in seven healthy subjects. In the single-application study, plasma clonidine concentration increased in a dose-dependent manner after application of M. Maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) increased in a dose-dependent manner, but the difference did not reach significance. Time to maximum concentration, elimination half-life, and total and renal clearance did not differ significantly among three trials. Blood pressure (BP) decreased gradually after application of each dose of M. The BP-lowering effect of M 8 mg was greater than that of M 4 mg and 6 mg. Adverse effects such as erythema and drowsiness were reported in some subjects. No subject had to be withdrawn from the study because of the appearance of adverse effects. In the repeated-application study, plasma concentration of clonidine increased up to 48 hours after application of first patch, and thereafter remained within a relatively narrow range until removal of third patch. The Cmax and AUC did not differ significantly among three trials. Blood pressure during an active period decreased significantly during treatment with M, whereas BP at midnight did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

PubMed1993

Effects of diltiazem and cimetidine on theophylline oxidative metabolism.

The effect of diltiazem or cimetidine pretreatment on the inhibition of theophylline oxidative metabolism was investigated in nine healthy male nonsmokers. Diltiazem 60 mg, cimetidine 400 mg, or placebo was given orally three times daily for 3 days in a randomized three-way crossover manner. Both diltiazem and cimetidine pretreatment decreased the mean theophylline clearance (0.702 on placebo versus 0.641 on diltiazem, P < .05, and 0.542 mL/minute/kg on cimetidine, P < .01), resulting in prolonged mean theophylline half-life (7.58 on placebo versus 8.59 on diltiazem, P < .05, and 10.08 hours on cimetidine, P < .01) with no change in volume of distribution. The mean metabolic clearances for three major theophylline metabolites, 1-methyluric acid (1-MU), 1,3-dimethyluric acid (1,3-DMU), and 3-methylxanthine (3-MX), were reduced significantly by cimetidine (28%; P < .05, 32%; P < .01, and 33%; P < .01, respectively). Conversely, diltiazem significantly reduced only the mean metabolic clearance of 1,3-DMU by 21% (P < .05) without changes in that of 1-MU or 3-MX. These results suggest that cimetidine inhibited both N-demethylation and 8-hydroxylation of theophylline, whereas diltiazem exerted little influence on N-demethylation in spite of inhibition in 8-hydroxylation.

Adult↗

PubMed1993

The influence of pretreatment periods with diltiazem on nifedipine kinetics.

The effect of durations of diltiazem pretreatment on nifedipine kinetics was evaluated. Eighteen healthy male subjects were randomly allocated to three groups, 6 subjects each, for single doses of 60 mg diltiazem, and 3 days and 6 days with diltiazem 60 mg three times a day. All subjects received 20 mg nifedipine orally on two occasions using a double-blind cross-over, placebo-controlled method. No significant difference on pharmacokinetic parameters of nifedipine without diltiazem were observed among three groups. The single dose with 60 mg diltiazem significantly increased the area under the plasma concentration-time curve (AUC) for nifedipine compared with that in control an average of 35.1% (P < .05) and decreased the total body clearance (CL) an average of 24.0% (P < .05). Three days and 6 days pretreatment with diltiazem 60 mg three times a day significantly increased mean nifedipine AUC to 151.1% (P < .01), 188.0% (P < .05) of control values, and decreased CL to 58.2% (P < .01), 63.9% (P < .05) of control values, respectively. The elimination half-life (t1/2) of nifedipine were significantly prolonged both after 3 days' and after 6 days' pretreatment of diltiazem. These results suggest that diltiazem affects the nifedipine kinetics rapidly and pretreatment duration dependently. A clinically important drug interaction may occur when both drugs are administered simultaneously.

Administration, Oral↗

PubMed1993

Influence of lisinopril on urinary electrolytes excretion after furosemide in healthy subjects.

It has been reported that the urinary excretions of chloride (Cl), potassium (K), and magnesium (Mg), but not sodium (Na), after furosemide, a loop diuretic, were decreased by pretreatment with lisinopril, an ACE inhibitor in hypertensive subjects. The electrolytes disturbance induced by furosemide might be ameliorated by lisinopril. The present study re-examines this potential drug interaction in healthy subjects. Lisinopril (20 mg) or its matching placebo was given orally using a double-blind, crossover design. Four hours after lisinopril administration, furosemide (20 mg) was injected intravenously and urine was collected during the following intervals: 0-0.5, 0.5-1, 1-1.5, 1.5-2, 2-3, 3-4, and 4-6 hours. Blood samples for plasma furosemide concentration were obtained at 0.5, 1, 1.5, 2, 3, 4, and 6 hours after the agent. There were no significant differences between the two trials in plasma concentrations of furosemide or urinary excretions of the agent. Urine volume and urinary excretions of electrolytes (Na, Cl, K, and Mg) after the furosemide with lisinopril administration were not significantly different from those of placebo at any observation period. These results suggest that the urinary excretions of electrolytes after furosemide administration are not influenced by pretreatment with lisinopril.

Adult↗

PubMed1993

The effect of nifedipine on the pharmacokinetics and dynamics of diltiazem: the preliminary study in normal volunteers.

To evaluate the influence of nifedipine on the pharmacokinetics and the pharmacodynamics of diltiazem, five healthy subjects received 60 mg diltiazem orally on two occasions, diltiazem alone or after nifedipine pretreatment (10 mg three times daily for 3 days). After nifedipine pretreatment, the maximum concentration (Cmax) of diltiazem was increased and the time of Cmax was shortened, and the area under the concentration curve (AUC) tended to be increased. Although heart rate was increased, the corrected PQ interval tended to be prolonged after the nifedipine pretreatment. Both a decreased hepatic clearance and an increased bioavailability of diltiazem probably accounts for the increase in the Cmax and AUC of diltiazem after nifedipine pretreatment, and that might affect the pharmacodynamics of diltiazem.

Administration, Oral↗

PubMed1993

Differences of chronopharmacokinetic profiles between propranolol and atenolol in hypertensive subjects.

Previous studies have shown that the absorption rate of a lipophilic, but not hydrophilic, agent is faster after the night dosage than after the morning dosage in nocturnal rodents. The present study examines whether such a difference in chronopharmacokinetic profiles between lipophilic and hydrophilic agents also exists in humans. Propranolol (20 mg), a lipophilic beta-blocker, or atenolol (50 mg), a hydrophilic beta-blocker, was given orally to 13 hypertensive patients at 9:00 AM (day trial) or 9:00 PM (night trial) by a crossover design. Plasma concentrations of propranolol and its metabolites, 4-hydroxypropranolol and naphthoxylactic acid, and atenolol were determined just before and at 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours after treatment. Maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of propranolol in the day trial were significantly greater than those in the night trial. Time to maximum plasma concentration (tmax) was significantly shorter in the day trial. No significant difference was observed in the elimination half-life between the two trials. There were similar administration time-dependent changes in the Cmax for 4-hydroxypropranolol and naphthoxylactic acid. On the other hand, although the Cmax of atenolol was greater and its tmax was shorter in the day trial, the differences did not reach significance. These results suggest that propranolol, but not atenolol is absorbed more rapidly after the morning dosage than after the night dosage. Based on these findings, the authors speculate that the absorption rate of a lipophilic, but not hydrophilic, agent is faster after the morning dosage than after the night dosage in humans.

Administration, Oral↗