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Y Tomono

Publications and source records attributed to Y Tomono.

At least 55 records · Page 3Linked to original sources
PubMed1994

Phase I study of E1077, a novel parenteral cephem antibiotic.

The safety and pharmacokinetics of E1077, a new injectable cephem antibiotic, were evaluated in healthy male adult volunteers. In the single-dose studies, 100, 250, 500, 1,000, and 2,000 mg of E1077 were administered by intravenous infusion at a constant rate for 60 minutes, then 1,000 mg of the drug by intravenous infusion at a constant rate for 5 minutes. The Cmax were 6.4, 15.7 +/- 12.0, 34.7 +/- 4.6, 63.2 +/- 4.6, 142.7 +/- 5.6, and 131.6 +/- 36.0 (means +/- SD) micrograms/mL, respectively, and the Cmax and AUC increased linearly with the dose. Plasma concentration-time curves were well described by a two-compartment open model. The plasma elimination half life of the drug was 1.88 +/- 0.15 hours. The mean urinary recovery within the first 24 hours was 94.1 +/- 5.1% of the dose. In the multiple-dose study, 2,000 mg of E1077 was intravenously administered at a constant rate over 60 minutes every 12 hours for 4.5 days (a total of nine times). The Cmax after the first and ninth doses were 134.0 +/- 17.4 and 135.5 +/- 15.5 micrograms/mL, respectively, and trough levels in day 1 and day 5 (at 12 hours after the first and ninth administration, respectively) were 2.2 +/- 0.8 and 1.9 +/- 0.4 micrograms/mL, respectively. No accumulation of the drug in plasma was observed. There were no significant differences in plasma levels or in the urinary recoveries between the single- and multiple-dose regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Pharmacokinetic properties of E3810, a new proton pump inhibitor, in healthy male volunteers.

E3810 is a new H+,K(+)-ATPase inhibitor with a substituted benzimidazole, which is under clinical investigation for peptic ulcer treatment in Japan and the USA. Three separate studies were conducted to evaluate the safety and to establish the pharmacokinetic profile of E3810 after oral administration to healthy male subjects. E3810 was administered as: single oral doses (1, 3, 10, 20, 40 and 80 mg) in fasting conditions, a single oral dose (20 mg) after a meal and repeated oral doses (20 and 40 mg) once daily for 7 days. The concentrations of E3810 and its metabolites in plasma and urine were determined by HPLC methods with UV detection. E3810 was generally well tolerated by all subjects. In the single-dose study, Cmax and AUC increased with increasing doses in the dose range examined. The mean plasma half-life was about 1.0 hour and was dose-independent. The apparent oral clearance of E3810 ranged from 4.37 to 8.40 ml/min/kg. No significant deviation from linear pharmacokinetics was observed. Approximately, 30% of a dose was excreted into the urine as thioether carboxylic acid-E3810 and its glucuronide. The mean serum protein binding was 96.3%. No effect of food intake on the Cmax and AUC was observed while tmax after a meal was 1.7 hours longer than that in the fasting conditions. No appreciable change in drug pharmacokinetics was observed during repeated oral dosing of E3810.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

Aquaretic effect of the stable dynorphin-A analog E2078 in the human.

Dynorphin-A is an endogenously released hormone that is now recognized as a kappa-opioid receptor agonist. Because kappa-agonists have been reported to induce water diuresis through negative modulation of antidiuretic hormone release and/or action, in the present study we investigated the aquaretic effects and safety of E2078, a metabolically stable dynorphin-A analog, in 21 healthy subjects after single (1.0, 2.0, 3.0, 5.0, 7.5 and 10.0 mg, i.m.) and repeated (5.0 mg t.i.d. for 4 and 1/3 days) administration. E2078 dose-dependently increased the 0 to 4-hr urine volume, which plateaued between 1032.4 +/- 130.1 and 1286.2 +/- 113.0 ml/4 hr (mean +/- S.E.M.) at doses of between 5.0 and 10.0 mg. The drug decreased urine osmolality (Uosm) markedly, by 17 to 27%, and the free-water clearance (CH2O) became positive, changing from -1.8 +/- 0.2 (placebo) to 0.8 +/- 0.3-2.8 +/- 0.4 ml/min after a single E2078 administration (P < .01). In the repeated-dose study, the first dose of E2078 increased the 0 to 5-hr urine output (1256 +/- 164.9 ml/5 h), lowered Uosm (151.8 +/- 13.3 mOsm/kg) and brought about a positive CH2O (1.9 +/- 0.2 ml/min). These values were similar to those seen after the single dose, but after the subsequent doses these aquaretic effects were attenuated, although the ranges of these same parameters were still significantly greater (P < .01-0.05) (441.4 +/- 102.4-585.3 +/- 131.9 ml/5 hr, 322.8 +/- 21.9-378.2 +/- 47.7 mOsm/kg and -0.2 +/- 0.2-(-)0.6 +/- 0.2 ml/min, respectively) than the day -1 base line (164.1 +/- 41.3 ml/5 hr, 992.0 +/- 80.6 mOsm/kg and -1.2 +/- 0.2 ml/min, respectively). Urinary excretion of electrolytes (Na, K and Cl) was not altered during either study period. A single E2078 administration reduced plasma antidiuretic hormone dose-dependently. On repeated dosing, the plasma concentration had rebounded to approximately 3 pg/ml by the time of the first dose on days 3 and 5, which lowered it again. The present results suggest that E2078 is a safe and effective aquaretic and could be a useful therapeutic tool for patients with water-retaining diseases.

Adult↗
PubMed1993

Comparison of the pharmacokinetics of E2020, a new compound for Alzheimer's disease, in healthy young and elderly subjects.

E2020, a central-acting cholinesterase inhibitor, is now under clinical development as a potential therapeutic agent for senile dementia of Alzheimer type. In the current study, the authors compared the pharmacokinetics of this drug after single oral administration in 12 healthy young volunteers (20-27 years of age) and 6 elderly volunteers (65-82 years of age). The subjects received a single 2-mg oral dose of E2020 after a meal. Blood samples for determination of the drug level were collected over 168 hours after drug administration and were measured by specific high-pressure liquid chromatography methods with ultraviolet detection. E2020 was generally well tolerated by all subjects of both groups. The plasma elimination half-life of the beta-phase (t 1/2 beta) and time to maximum peak plasma concentration (tmax) were significantly longer in the elderly than in the young: t 1/2 beta, 103.8 +/- 40.6 versus 59.7 +/- 16.1 hours; and tmax, 5.2 +/- 2.8 versus 3.4 +/- 1.5 hours, respectively. There were no statistically significant differences in maximum peak plasma concentration and area under the curve between the two groups. The mean (+/- standard deviation) oral clearance (Cl/F) in the elderly (9.1 +/- 2.4 L/h) was similar to that in the young (10.6 +/- 2.7 L/h). The volume of distribution in the steady state (Vdss/F) was significantly larger in the elderly than that in the young: 1217.2 +/- 223.2 versus 852.5 +/- 147.7 L, respectively. These results suggested that the drug was absorbed more slowly and distributed more widely and thoroughly, but that its clearance from the body is essentially unaffected by age.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Pharmacokinetics of E2020, a new compound for Alzheimer's disease, in healthy male volunteers.

E2020 is a new cholinesterase inhibitor with a novel chemical structure, which is under clinical investigation for use in Alzheimer's disease in Japan and the USA. Three separate studies were conducted to evaluate the safety and to establish the pharmacokinetic profile of E2020 after oral administration to healthy male subjects. E2020 was administered as: (1) single oral doses (0.3 mg, 1 mg, 2 mg, 5 mg, 8 mg and 10 mg) in a fasting condition, (2) a single oral dose (2 mg) after a meal and (3) repeated oral doses (2 mg once daily for 21 days). The concentrations of E2020 and its metabolites in plasma, serum, urine and feces were determined by HPLC methods with UV detection. E2020 was generally well tolerated by all subjects. In the single-dose study, there was a linear relationship between dose and mean AUC. The mean plasma half-life was about 50 hours and was dose-independent. The total clearance and renal clearance of E2020 were also dose-independent and the mean values after 10 mg dosing were 9.7 l/hour and 0.86 l/hour, respectively. The cumulative total urinary and fecal excretion of the sum of unchanged E2020 and its metabolites at 264 hours after the administration of the single 10-mg-dose was 36.1% and 8.6% of the dose, respectively. The mean serum protein binding was 92.6%. No effect of food intake on the pharmacokinetics was observed. Evaluation of the mean trough levels and AUC0-24 of E2020 indicated that a steady-state was achieved after approximately 2 weeks of daily dosing.

Adult↗
PubMed1991

Aspergillus mycotic aneurysm--case report.

A 61-year-old female developed subarachnoid hemorrhage after trans-sphenoidal surgery for Rathke's cleft cyst. Neuroradiological examination revealed a large aneurysm at the C1 portion of the right internal carotid artery. Autopsy revealed marked proliferation of aspergillus hyphae in the wall of the aneurysm. A review of previously reported cases of fungal aneurysm proposes two developmental processes. Aneurysms secondary to fungal meningitis tend to be large in size and located in the major cerebral artery trunk, but aneurysms following fungal sepsis tend to be small and in peripheral branches. The former aneurysms are probably caused by fungus invasion into the intracranium, usually from the paranasal sinus, and the latter may be due to fungal emboli like bacterial emboli in bacterial endocarditis. Ruptured fungal aneurysms are difficult to treat, so fungal meningitis or sepsis must be eradicated before an aneurysm develops.

Aneurysm, Infected↗
PubMed1990

High-performance liquid affinity chromatography and in situ fluorescent labeling on thin-layer chromatography of glycosphingolipids.

A method combining high-performance liquid affinity chromatography and in situ fluorescent labeling on thin-layer chromatography is introduced for determination of glycosphingolipids. Glycolipids in crude extract from rat liver were separated quantitatively from neutral lipids and phospholipids with a phenylboronic acid-derivatized silica gel column. Glycolipids were eluted quantitatively with approximately 98% of crude extract recovered. This column is useful for selective cleanup of glycosphingolipids in crude extract from tissue. Simultaneously, a fluorometric determination of glycosphingolipids with 7-amino-4-methylcoumarin after NaIO4 oxidation on a TLC plate was introduced and its condition was optimized. Glycolipids in amounts ranging from 1 to 100 pmol are easily detectable and give linear responses over the respective ranges. The method is fast and useful for the determination of glycolipids from small amounts of biological samples and requires a minimum amount of about 1 mg of biological specimen for determination of glycolipids.

Animals↗
PubMed1990

Suprasellar ectopic pituitary adenoma: case report and review of the literature.

The occurrence of a totally suprasellar ectopic pituitary adenoma in a 71-year-old man is described. The tumor was attached to the pituitary stalk, extending upward toward the third ventricle. No intrasellar lesion was observed. Histological examination revealed a pituitary adenoma with large numbers of eosinophilic cells with moderate nuclear polymorphism and rare mitosis. Immunohistochemical staining revealed that the tumor cells were strongly positive for anti-adrenocorticotropic hormone antibody. A review of five previously reported intracranial ectopic pituitary adenomas revealed that two were silent corticotropic tumors and two occurred with Cushing's syndrome.

Adenoma↗
PubMed1989

Phase I study of E1040, a new parenteral cephem antibiotic.

The safety and pharmacokinetics of E1040, a new injectable cephem antibiotic, were evaluated in healthy volunteers. In single-dose studies, 125, 250, 500, 1000 and 2000 mg of E1040 were administered by I.V. infusion over 1 hour. Results of 5 minutes I.V. infusions of 500, 1000 and 2000 mg of the drug were also studied. Plasma concentration-time profiles were well suited to a two-compartment open model. The half-life of elimination from plasma was 1.85 +/- 0.16 hours, and the Cmax and AUC paralleled the doses given. The mean urinary recovery within the first 24 hours was 85.7 +/- 6.43% of the dose. In a multiple-dose study, 2000 mg of E1040 (I.V. over 1 hour) was administered every 12 hours (total 9 times) and no abnormal accumulation of the drug in plasma was observed. There were no significant differences in plasma levels or in urinary recoveries between single- and multiple-dose regimens. There were no subjective or objective abnormal findings definitely attributable to the drug except that one subject given 250 mg over 1 hour reported diarrhea, and another complained of nausea during the infusion of 2000 mg over 5 minutes. From these results E1040 was concluded to be safe and well tolerated.

Adult↗
PubMed1988

[Functional and morphological analysis on GH producing adenomas with quantitative immunohistochemical method].

We studied functioning cells of GH-producing pituitary adenoma quantitatively by the immunohistochemical method using anti GH antibody and compared the result with clinical hormonal data by discussing a clinical significance of the immunohistochemical study of pituitary adenoma. Fifteen acromegalics with pituitary adenoma, who underwent surgical operation followed by immunohistochemical study, were subjected. Volume of the adenoma was calculated on the basis of thin coronal cut CT scanning. The specimen was stained after PAP method. The quantitative analysis was done by investigating the ratio of anti GH antibody positive area in 30 fields (SAR). Using the value obtained, stained volume (SV) was calculated by multiplying total volume by SAR. The SV was regarded as total volume of GH positive cells. These values were compared to the preoperative serum GH levels. The results were as follows: (1) Immunohistochemically, the adenomas were classified into two types, the sporadic type and the diffuse type, by incidence of GH positive cells. SAR ranged from 0.2% to 52.4%, and means of the types were 3.0% and 24.8%, respectively. (2) All the eosinophilic adenomas demonstrated to be the diffuse type and the mean SAR was 23.7%. On the contrary, 75% of chromophobe adenomas were the sporadic type and the mean SAR was 4.9%. (3) There was no significant correlation between the serum GH level and the volume of the adenoma. There was an especially high correlation between the serum GH level and SV with a correlation constant of 0.971. (4) In fibrous adenomas the serum GH level was extremely low for their total volume.

Adenoma↗
PubMed1987

Pituitary adenoma composed of two compartments each secreting prolactin or growth hormone.

We report a case of pituitary adenoma with two compartments, i.e. a part within the sella turcica and a part infiltrating the sphenoid bone beneath the sella, producing growth hormone (GH) and prolactin. The patient had the amenorrhea-galactorrhea syndrome, but not acromegalic symptoms. Although the two compartments were united through a small dural perforation, immunohistochemical studies demonstrated that GH and prolactin were separately secreted from the intrasellar and extrasellar components, respectively. Somatotropic adenomas frequently produce prolactin, but it is unusual for these hormones to be secreted from distinctly different parts of the same lesion.

Adenoma↗
PubMed1986

Estimation of growth fraction with bromodeoxyuridine in human central nervous system tumors.

Twenty-five patients with tumors of the central nervous system received bromodeoxyuridine (BUdR), 200 mg/sq m, by intravenous infusion every 8 hours for 3 days before surgery. Excised tumor specimens were fixed in chilled 70% ethanol, embedded in paraffin, and cut into 6-micron sections. Each section was reacted with monoclonal antibodies against BUdR and stained with immunoperoxidase to identify nuclei that had incorporated BUdR. The growth fraction of each tumor was estimated by calculating the ratio of BUdR-positive nuclei to the total number of tumor cells in three to six microscopic fields in viable areas of the tumor. In seven cases, the tumor doubling time was measured from the serial computerized tomography scans and an attempt was made to estimate the cell cycle time. The growth fractions ranged from 9.1% to 46.5% in malignant gliomas, 2.0% to 6.7% in low-grade gliomas, 11.2% to 43.2% in metastatic brain tumors, 0.8% to 1.9% in pituitary adenomas, 3.9% to 4.6% in acoustic neurinomas, and 6.2% to 8.2% in meningiomas and cerebellar hemangioblastomas. The estimated cell cycle time was 5 to 12 days in most malignant gliomas and brain metastases; however, the actual cell cycle time should be substantially shorter because cell loss was not considered in the calculation. Although the growth fraction appeared to correlate with the biological malignancy of each tumor, the tumor doubling time did not reflect growth potential. It is possible that unpredictable cell loss plays an important role in tumor growth at certain sizes. Therefore, the cell cycle times calculated in this study are considerably overestimated and should be interpreted with caution.

Bromodeoxyuridine↗
PubMed1986

Pharmacokinetic study of deuterium-labelled coenzyme Q10 in man.

The pharmacokinetics of coenzyme Q10 (CoQ10) in man was studied by utilizing deuterium-labelled coenzyme Q10 (d5-CoQ10). The absence of an isotope effect in the disposition of d5-CoQ10 in man was confirmed from the plasma concentration time curves after simultaneous oral dosing of d5-CoQ10 and unlabelled CoQ10. After oral administration of 100 mg of d5-CoQ10 to 16 healthy male subjects, the mean plasma CoQ10 level attained a peak of 1.004 +/- 0.370 micrograms/ml at 6.5 +/- 1.5 h after administration, and the terminal elimination half-life was 33.19 +/- 5.32 h. In most of the subjects, plasma d5-CoQ10 showed a second peak at 24 h after dosing. This unusual plasma level curve was well described by a newly proposed compartment model based upon the assumption that absorbed CoQ10 is taken up by the liver and then transferred mainly to VLDL and redistributed from the liver to the systemic blood.

Administration, Oral↗
PubMed1985

Plasma concentrations of lidocaine and its principal metabolites during intermittent epidural anesthesia.

Plasma concentration-time courses of lidocaine and its principal metabolites (monoethylglycinexylidide, MEGX, and glycinexylidide, GX) were studied during intermittent epidural injections of lidocaine HCl in eight female patients (ASA status 1). The initial dose (320-400 mg without epinephrine) followed by top-up injections of about 60% of the mean initial dose every 35-55 min resulted in a plasma accumulation of lidocaine: the peak concentration increased from 2.30 +/- 0.46 (mean +/- SD) microgram/ml following the first injection and 3.34 +/- 0.76 microgram/ml after the second, to 4.11 +/- 0.72 microgram/ml following the third. The maximum concentrations of MEGX and GX were 0.66 +/- 0.22 and 0.28 +/- 0.08 microgram/ml, respectively. A pharmacokinetic model could successfully fit the entire plasma concentration-time profile of lidocaine during repeated epidural injections (r2 = 0.886 to 0.983). Such pharmacokinetic variables as elimination half-life (t1/2, 2.33 +/- 0.43 h), apparent volume of distribution divided by bioavailability (Vd/F, 2.51 +/- 0.61 l/kg), and clearance divided by bioavailability (Cl/F, 11.65 +/- 1.21 ml X kg-1 X min-1) obtained from the female patients were in reasonable agreement with those reported from healthy females receiving the intravenous lidocaine HCl. A computer-aided simulation generated from using the mean kinetic data in a 50-kg woman predicted that plasma lidocaine concentration would reach the postulated toxic range (approximately equal to 6 microgram/ml) after the fourth supplementary dose under a similar dosing scheme as performed in this study. In conclusion, an accumulation of lidocaine in plasma occurs during a usual intermittent epidural dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Glycosphingolipid patterns of rat kidney. Dependence on age and sex.

The composition and quantity of glycosphingolipids in kidney from 3-50-week-old male and female rats have been investigated. Glycosphingolipids were separated by high-performance liquid chromatography on a diethylaminoethyl-porous glass and porous glass column followed by high-performance thin-layer chromatography. The quantity of neutral glycolipids in male rat kidney decreased significantly between 3 and 25 weeks; the quantity in 25-week-old kidney became half the quantity found in 3-week-old kidney and remained constant thereafter. The quantity of neutral glycolipids in female rat kidney did not show age-dependent changes. The composition of neutral glycolipids revealed by high-performance thin-layer chromatography was constant, regardless of age and sex. Monoglycosylceramide and tetraglycosylceramide were the major compoments at all ages in both sexes. In contrast to the patterns of neutral glycolipids, ganglioside content was higher in female rats than males, and total ganglioside content increased in both sexes with increasing age. The most remarkable change was an increase of disialoganglioside in female rat kidney between 5 and 25 weeks. The ratio of disialogangliosides to monosialogangliosides (D/M value) in female rat kidney increased 4-fold during this period. The ganglioside pattern in female rat kidney was affected by spaying. The quantity of disialogangliosides decreased rapidly on the 7th day after spaying, but the level went back to normal on the 14th day after spaying. The data strongly suggest that sex hormones influence glycosphingolipid synthesis in rat kidney.

Aging↗