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Biomedical subjects

M Kanamaru

Publications and source records attributed to M Kanamaru.

At least 37 records · Page 2Linked to original sources
PubMed1994

Pharmacokinetics and safety of intravenous recombinant human superoxide dismutase (NK341) in healthy subjects.

Recombinant human superoxide dismutase (rhSOD), NK341, was intravenously administered to healthy male volunteers at doses of 1750-35000 U/kg, and the safety and pharmacokinetic properties were evaluated. There were no abnormal findings attributable to the test drug throughout the study, showing that NK341 was well tolerated in healthy subjects. Tri-exponential elimination of the drug from blood was observed with half-lives of about 20 minutes (alpha phase), 80 minutes (beta phase), and 6 hours (gamma phase). The values of the maximal plasma concentration and the areas under the plasma concentration curves linearly increased with the doses given. On the other hand, the urinary recovery of the drug also increased with the dose, ranging approximately from 3%-45% of the dose. The plasma concentration of the drug measured by an enzyme immunoassay was quite comparable to SOD activity measured by electron spin resonance, suggesting that NK341 was present in blood as the active form of SOD.

Adult↗
PubMed1993

Aldose reductase inhibitory and uricosuric activities of FK366 in healthy volunteers.

The pharmacokinetics, and aldose reductase (AR) inhibitory and uricosuric activities of FK366 were studied in healthy volunteers given a single oral dose of 150, 300, or 600 mg after fasting, 600 mg after a meal, or 300 mg twice a day for 8 days after meals. The AR inhibition was assessed by the percent reduction from the predrug dulcitol values in red blood cells converted from exogenous galactose by AR. Aldose reductase inhibition paralleled the plasma concentrations of FK366, with maximum inhibitions of 31.6, 48.0, and 56.9% at doses of 150, 300, and 600 mg, respectively. With multiple dosing, the inhibition scarcely differed between the first (41.8%) and last doses (41.5%). Serum uric acid decreased dose dependently, with a minimum concentration of 4.0 mg/dL (predrug: 5.5 mg/dL) 8 hours after receiving 600 mg. With multiple dosing, serum uric acid levels declined rapidly and remained at a concentration of 3.1 mg/dL beginning at day 3. Urinary excretion of uric acid was high on day 1 (879 mg/day), but decreased significantly to 654 mg/day on day 2 and then stabilized. The pharmacokinetics of FK366 were linear over the dose range studied, with an elimination half-life of 8.2 hours and urinary recovery of 27.2% as unchanged drug. FK366 was well tolerated by all subjects.

Adult↗
PubMed1993

Phase I study of DQ-2556, a new parenteral 3-quaternary ammonium cephalosporin antibiotic.

The safety and pharmacokinetic properties of DQ-2556, a new parenteral cephalosporin, were evaluated using healthy volunteers after 5-minute intravenous infusion of doses of 250, 500, 1000, or 2000 mg and a 1-hour infusion of 2000 mg, and an intramuscular dose of 500 mg. The half-lives of DQ-2556 ranged from 1.64 to 2.15 hours. The peak serum concentrations and area under the curve values were linearly correlated to the doses. The mean urinary recoveries were 80.0 to 85.5% of a dose within 24 hours. Salivary concentrations of the drug were low. There was no accumulation of DQ-2556 after 9 administrations every 12 hours. DQ-2556 was well tolerated.

Adult↗
PubMed1993

The pharmacokinetics of the beta 2-adrenoceptor agonist, tulobuterol, given transdermally and by inhalation.

We have studied the pharmacokinetics of tulobuterol given transdermally or by aerosol inhalation in healthy male volunteers. Tulobuterol was rapidly absorbed after inhalation, with a tmax of 0.8-1.5 h. The Cmax and the AUC increased linearly with dose. Tulobuterol was well absorbed after transdermal administration, with an absorption lag-time of about 4 h. The Cmax and AUC increased linearly with dose and the tmax was about 9-12 h. The mean percentage of drug absorbed during the application of a patch for 24 h was 82-90% after a single dose and 82-85% during repeated dosing. The mean urinary recoveries as unchanged drug after a single inhalation and patch application were 3-4% and 5-6% respectively. Tulobuterol did not accumulate during repeated inhalation or transdermal application. It was well tolerated, except for an increase in heart rate of 10-20 beats.min-1 after five repeated applications of a 4 mg patch.

Administration, Cutaneous↗
PubMed1992

Pilot study of the uricosuric effect of DuP-753, a new angiotensin II receptor antagonist, in healthy subjects.

The uricosuric effect of DuP-753, a novel, specific angiotensin II receptor antagonist, has been explored in a healthy male Japanese volunteers, given single oral doses of 25, 50, 100 or 200 mg (n = 6), or 100 mg (n = 6) or placebo (n = 3) once daily for 7 consecutive days. In the single-dose study, serum uric acid measured at 4 h after dosing showed a dose dependent decrease; the reductions from the corresponding pre-dose values were: 0.32 (25 mg), 0.77 (50 mg), 1.25 (100 mg) and 1.33 mg.dl-1 (200 mg). The urinary excretion of uric acid within the first 4 h after treatment was also increased in a dose-dependent manner, whereas the urinary excretion of creatinine remained unchanged. In the multiple-dose study, DuP-753 significantly decreased the serum uric acid concentration measured 4 h both after the first (pre-dose value: 5.68 vs 4 h after: 4.48 mg.dl-1) and last administrations (4.42 mg.dl-1). Simultaneously, the ratio of urinary uric acid to creatinine excretion was significantly increased within the first 4 h both after the first (DuP-753: 1.190 vs placebo: 0.576) and last administrations (1.02 vs 0.576). The findings suggest that DuP-753 possesses a uricosuric effect both after single and multiple doses in healthy subjects. The effect should be further examined in hypertensive patients.

Adult↗
PubMed1992

Multiple endocrine neoplasia type 2A.

A 40-year-old woman was admitted with complaints of headache, palpitation and diaphoresis. She had undergone right hemithyroidectomy 12 years previously. Histological reexamination of the operative specimen revealed a medullary thyroid carcinoma. Abdominal ultrasonography, CT scan and angiography showed bilateral adrenal tumors. Serum catecholamine levels in both adrenal veins were high. Based on these data, bilateral adrenalectomy was performed. Histological examination confirmed the diagnosis of pheochromocytomas. After operation, serum calcitonin and urinary noradrenaline levels were still high. Further examination by 131I-metaiodobenzylguanidine (MIBG) scintigraphy is planned.

Adrenal Gland Neoplasms↗
PubMed1992

Two cases of oral-stings by sperm bag of squid.

Two patients after eating raw squid complained of severe pain and foreign body sensation in their oral cavity. On consultation of a doctor, several small spindle-shaped stings stuck on the surface of the tongue and mucous membrane of the oral cavity were found. After all stings were pulled out, the pain was allayed and the wounds eventually healed. The foreign bodies were tentatively determined to be the sperm bag of Tadorodes pacificus. These cases suggest that fresh squids should be carefully prepared before eating them raw or "sashimi".

Adult↗
PubMed1992

[Clinico-pharmacological evaluation of omeprazole, as a proton pump inhibitor, compared with H2-blockers].

We evaluated the safety, tolerance, pharmacokinetics and pharmacodynamics of omeprazole, a new anti-ulcer agent chiefly on the basis of our studies in healthy male volunteers. The type and incidence of side effects of omeprazole have been reported to be similar to those of H2-antagonists, and in our studies too, omeprazole was estimated to be safe and tolerable. Following single doses, the increase in AUC was not proportional to the increase in dosage. In the multiple-dose study, the AUC was greater on day 7 than on day 1. This finding may be due to a partial saturation of first pass elimination. Repeated omeprazole treatment (20 mg once daily for 4 days) inhibited the basal and stimulated acid secretion. Though H2-blockers inhibit the basal and stimulated pepsin secretion, omeprazole inhibited the stimulated pepsin secretion only.

Adenosine Triphosphatases↗
PubMed1992

Pharmacokinetics of the new antiplatelet agent 2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine in human subjects.

The pharmacokinetics of KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine, CAS 94457-09-7) was studied in healthy male adult volunteers after single ascending oral dose and multiple dosing for 7 days. Serum KC-764 concentration attained the peak in 1 h and declined with a half-life of about 2 h at a single oral dose of 5, 10, 20 and 40 mg. No dose dependent pharmacokinetics of KC-764 was demonstrated. Three metabolites were detected in serum, but their concentrations were lower than that of KC-764. 48-h urinary recoveries after single doses were 41.6-46.6% of dose, not being dose-dependent. Urinary recovery of unchanged KC-764 was 1.1-1.6% of dose. Three metabolites were present in greater amount in urine than unchanged KC-764 and two metabolites were less than KC-764. There was little daily variation of serum concentrations and urinary excretion of KC-764 and its metabolites in the multiple dosing (20 mg twice a day) study. The daily and total urinary recovery were same as those after single doses. Food reduced Cmax and tended to delay tmax, but did not influence AUC0----infinity and urinary recovery. Serum protein binding of KC-764 was about 60%, being not dependent on total serum concentration.

Adult↗
PubMed1990

[IgA-lambda type myeloma complicating with autoimmune hemolytic anemia].

A 66-year-old female was admitted to our hospital with lumbago. On admission, laboratory examination revealed hemolytic anemia. Direct Coombs' test was positive, and also direct monospecific-Coombs' test by anti-C3d serum was positive. Immunoelectrophoresis showed IgA-lambda type M proteins in serum. Bone marrow aspiration disclosed increased atypical plasma cells. X-ray of skull showed punched-out lesion. From these findings, she was diagnosed as IgA (lambda) myeloma complicating with autoimmune hemolytic anemia. Hemolysis was improved by chemotherapy. It was thought that IgA and C3 were related well to hemolysis in this case.

Aged↗
PubMed1990

[A diffuse, pleural, malignant mesothelioma kept in long remission by chemotherapy combining pirarubicin and cisplatin].

Reported is the case of a 66-year-old male with a diffuse, pleural, malignant mesothelioma that has been successfully treated by combining cisplatin and doxorubicin. The patient received 100 mg of cisplatin and 50 mg of doxorubicin every 5 weeks, after which a regression of the tumor and a pleural effusion decrease was observed. After partial remission was achieved, the dosage was changed to 50 mg of cisplatin and 50 mg of pirarubicin on a five-week cycle. This led to a partial remission of two-years duration and the abatement of a doxorubicin-induced alopecia. The authors thus have concluded that a combined therapy of doxorubicin and cisplatin is effective for treating a malignant mesothelioma, and that pirarubicin is superior to doxorubicin with reference to side effects.

Aged↗
PubMed1989

Phase I study of Y-20811, a new long-acting thromboxane synthetase inhibitor by intravenous administration.

The safety, pharmacological action and pharmacokinetics of Y-20811, a thromboxane (TX) synthetase inhibitor, were investigated by single intravenous administration of 5, 10, and 25 mg each to six healthy adult male volunteers. Throughout the entire test period, no abnormality attributable to the test drug was found in subjective and objective symptoms, routine laboratory tests, physical tests, or bleeding time; and the drug was well tolerated by subjects. Inhibition of serum TXB2 production and an increase in 6-keto-prostaglandin (PG) F1 alpha production during whole-blood coagulation exhibited a dose-dependent change from 0.5 hours after administration. In addition, arachidonic acid (AA)-induced platelet aggregation was inhibited, and adenosine diphosphate (ADP)-induced secondary aggregation was also inhibited. The duration of these actions was long; inhibition of serum TXB2 production and the increase in 6-keto-PGF1 alpha production lasted for 168 hours after administration , and inhibition of platelet aggregation lasted for more than 48 h after administration. The initial phase half-life (t1/2 alpha) and final phase half-life (t1/2 beta) of Y-20811, calculated from the change in plasma concentration, were 0.1-0.3 hours and 1.9-3.1 hours, respectively. The area under the plasma concentration-time curve (AUC) increased in a dose-dependent manner, but the values of volume of distribution (Vss) and total clearance (CLt) were almost constant in any dose group. At each of the three doses, 60-64% of the dose was excreted in unchanged form, and 8-10% in conjugated form in the urine, within 48 hours after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1989

Phase I study of Y-20811, a new long-acting thromboxane synthetase inhibitor by oral administration.

The safety, pharmacological action and pharmacokinetics of the thromboxane (TX) synthetase inhibitor Y-20811, a prospective medication for ischemic vascular disorder, were investigated in Phase I clinical trials in which single and repeated doses were administered orally to 32 healthy adult male volunteers. In the single-dose study, subjects were given single doses of 2.5, 5, 10, 25, 50, and 100 mg; in the repeated-dose study, a single dose of 50 mg was administered daily for 5 days. In the repeated-dose study, slight elevation of liver function test parameters in 1 subject was observed, but throughout the trials, no abnormality attributable to the test drug was found in other routine laboratory tests, subjective and objective findings, vital signs (blood pressure, pulse rate, body temperature, respiration rate), ECG, or bleeding time; nor did any finding indicate a problem concerning the safety of Y-20811. In both single- and repeated-dose studies, inhibition of the serum TXB2 production and an increase in the 6-keto-prostaglandin F1 alpha production during whole-blood coagulation, and inhibition of arachidonic acid-induced platelet aggregation were observed from 1 hour after administration of Y-20811. The duration of these actions was long, the former two lasting 168 hours (1 week) and the latter 48-72 hours or more. Slight inhibition of adenosine diphosphate-induced secondary platelet aggregation was also observed. The maximum plasma concentration time (tmax) of Y-20811 was 0.5-1.1 hours. The initial-phase half-life (t1/2 alpha) was 0.8-1.1 hours and the final-phase half-life (t1/2 beta) was 4.7-9.2 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Gas chromatographic assay and disposition of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, in healthy volunteers.

Quantitative determinations of plasma concentrations of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, and its urinary metabolite, 6-chloro-2-pyridinecarboxylic acid (metabolite 1), were obtained using GC with a 63Ni electron-capture detector. 6-Chloro-2-pyridylmethyl nitrate was extracted from plasma with n-pentane. Metabolite 1 was extracted from acidic urine with ethylacetate, back extracted with 0.1 M NaHCO3, and methylated with boron trifluoride methanol reagent. The internal standard for metabolite 1 determination was prepared by propylation of metabolite 1 with boron trifluoride n-propanol reagent. The formation of the esters was confirmed by the GC-MS results. These methods proved to be sensitive and reproducible. A single dose of 6-chloro-2-pyridylmethyl nitrate (5, 10, 20, 40, or 60 mg) was given perorally to healthy volunteers. From the data, a large interindividual variability in the apparent plasma clearance was apparent (85.5 +/- 123 L/min; CV 144%). However, metabolite 1 was the main metabolite in human urine, and the interindividual variation was slight (CV 13%).

Administration, Oral↗
PubMed1989

Arterial-venous plasma concentration differences of 6-chloro-2-pyridylmethyl nitrate in humans after sublingual administration.

The plasma concentrations of 6-chloro-2-pyridylmethyl nitrate after sublingual administration were determined in six healthy male volunteers (venous plasma) and eleven patients (arterial plasma) with ischemic heart failure. The pharmacokinetics of the compound was investigated in volunteers. Plasma concentration-time data in each volunteer were found to fit a two-compartment open model with zero-order absorption. The pharmacokinetic parameters estimated from curve-fitting the plasma concentration-time data were as follow: Tmax 10 +/- 2.8 min, Cmax 8.16 +/- 2.48 ng/mL and CLP 6.16 +/- 1.79 L/min (means +/- S.D.). The arterial plasma concentrations (11.9 +/- 5.14 ng/mL) 7 min after sublingual administration were significantly higher (p less than 0.05) than those in venous samples (6.86 +/- 2.80 ng/mL). These results support that the arterial-venous gradient exists after administration of 6-chloro-2-pyridylmethyl nitrate in humans.

Administration, Sublingual↗
PubMed1989

[A case of remission induced in diffuse pleural malignant mesothelioma by the treatment with cisplatin and doxorubicin].

A 66-year-old male patient with diffuse pleural malignant mesothelioma was successfully treated with cisplatin and doxorubicin. He was admitted to our hospital because of massive pleural effusion. The diagnosis was made by pleural needle biopsy. He received 100 mg of cisplatin and 50 mg of doxorubicin every 5 weeks. Regression of the tumor and decrease of pleural effusion were observed after the treatment. A partial remission of 10 months duration was achieved. Cisplatin and doxorubicin were thought to be the most active cytotoxic agents in the treatment of malignant mesothelioma.

Aged↗
PubMed1988

Clinical pharmacokinetics and tolerance of fleroxacin in healthy male volunteers.

The tolerance and pharmacokinetics of fleroxacin were studied in healthy male adult volunteers. The peak serum concentrations of unchanged fleroxacin were about 1.5, 3 and 5 mg/l at 1-2 h after single oral doses of 100, 200 and 400 mg, respectively. The apparent serum elimination half-life was about 10 h, independent of the dose. Fleroxacin, demethyl fleroxacin and fleroxacin N-oxide excreted in urine over 3 days accounted for about 75%, 5% and 5%, respectively, of the doses. The urine concentrations of unchanged drug were dose-related; the mean concentrations, sustained over 24 h, were about 50, 100 and 150 mg/l after 100, 200 and 400 mg doses, respectively. Food intake did not significantly influence the serum concentration and urinary excretion. Steady state serum concentrations were achieved from day 3 onwards by repeated doses of twice-a-day dosage regimen and were 2-4 and 5-9 mg/l after 200 and 400 mg bid, respectively. The mean concentrations of unchanged drug in urine were about 200 and 300 mg/l at the respective dosages. The pattern of urinary metabolites was not changed by repeated doses and 90% of repeat doses was recovered in urine, including metabolites. The serum protein binding of fleroxacin was 32%. The saliva concentration was 40% of the total serum concentration or 60% of the free serum concentration. The faecal recovery over 3 days was 3% of the dose following a single 200 mg dose after a meal. The unchanged drug concentrations in faeces during 400 mg repeated dosing were 100-150 mg/kg. No severe dose-related side-effects were observed during the study.

Adult↗