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Biomedical subjects

Y Utsui

Publications and source records attributed to Y Utsui.

29 records · Page 2Linked to original sources
PubMed1981

Evidence for a synergistic interaction between phenytoin and phenobarbital in experimental animals.

Combined anticonvulsant effects of phenytoin and phenobarbital in mice and rabbits were studied using the isobolographic method which was based on the plasma concentrations of these drugs. Anticonvulsant activity of test drugs alone or in combination was determined by the method of maximal electroshock seizure test. Response of each animal to drug action was recorded as abolition of the tonic hindlimb extensor component of maximal electroshock seizure. It was demonstrated that the minimal effective plasma concentrations of phenytoin and phenobarbital alone for protection against maximal electroshock seizure was 5.9 +/- 0.2 and 18.1 +/- 0.4 microgram/ml (+/- SE) in mice and 14.7 +/- 0.5 and 17.5 +/- 0.6 microgram/ml (+/-SE) in rabbits, respectively. Isobolograms for mice and rabbits were constructed by identifying and plotting each responder and nonresponder for its corresponding plasma phenytoin and phenobarbital concentrations when these drugs were given in combination. The isoboles in mice and rabbits were concave bowing toward the origin, indicated synergism (potentiation). The apparent synergism between phenytoin and phenobarbital cannot be explained by changes in the amount of these drugs entering into the brain from the blood, since the relationship between brain and plasma concentrations of either drug was not altered by the presence of the other. These results, therefore, suggest that the synergistic action between these two anticonvulsants occurs within the central nervous system; this provides experimental support for the combined use of phenytoin and phenobarbital in the clinical treatment of epilepsy.

Animals↗
PubMed1980

Determination of haloperidol in human serum by radioimmunoassay.

A radioimmunoassay has been developed which enables accurate determination of haloperidol in human serum. Antiserum was prepared by immunizing guinea pigs with haloperidol (O-carboxymethyl)oxime derivative (III) coupled with bovine serum albumin. With the antiserum, 3H-haloperidol and dextran-coated charcoal, the assay of haloperidol in serum was possible over a concentration range of 1 to 50 ng/ml, using 0.1 ml of human serum without the need of an extraction procedure. Data obtained by radioimmunoassay are in good agreement with those obtained by gas chromatography. No appreciable cross-reactivity was observed neither with haloperidol metabolites nor with other butyrophenone neuroleptics. Serum levels of haloperidol in schizophrenic patients receiving single oral dosing (6 mg/subject) have also been determined.

Antibodies↗
PubMed1979

Relationships between plasma concentrations of diphenylhydantoin, phenobarbital, carbamazepine, and 3-sulfamoylmethyl-1,2-benzisoxazole (AD-810), a new anticonvulsant agent, and their anticonvulsant or neurotoxic effects in experimental animals.

The relationships between plasma concentrations of diphenylhydantoin (DPH), phenobarbital (PB), carbamazepine (CBZ), and 3-sulfamoylmethyl-1,2-benzisoxazole (AD-810), a new anticonvulsant agent, and their anticonvulsant and neurotoxic effects were studied in various species of animals. Anticonvulsant activities of test drugs were examined by the maximal electroshock seizure (MES) test. Neurotoxicities were determined by the rotorod performance test in mice and rats and by behavioral observations in rabbits, dogs, and monkeys. It was demonstrated that both the anticonvulsant effects and the neurotoxic effects of the drugs tested were more closely correlated with their plasma concentrations than with the dosages administered. There was a critical plasma concentration for each drug to show an anticonvulsant effect or to cause a neurotoxic effect in an individual animal. The critical plasma concentrations for anticonvulsant and neurotoxic effects of each drug were relatively constant among different species, with the exception of DPH in rabbits, which had twice the value in other species. The therapeutic ranges of plasma concentrations of DPH, PB, and CBZ determined in various species of animals coincided well with those recommended clinically. AD-810 was found to be effective against MES without signs of neurological toxicity in the ranges of plasma concentrations of 9.8 to 74.0, 10.8 to 95.0, 9.6 to 117.0, and 12.6 to 96.2 microgram/ml in mice, rats, rabbits, and dogs, respectively. These results seem to suggest that AD-810 may be effective clinically at plasma concentrations above 10 microgram/ml, with a therapeutic range up to 70 microgram/ml, which is much wider than the therapeutic ranges of DPH (10--20 microgram/ml), PB (10--30 microgram/ml), and CBZ (4--10 microgram/ml).

Animals↗
PubMed1978

Determination of 7-chloro-3-(4-methyl-1-piperazinyl)-4h-1,2,4-benzothiadiazine-1,1-dioxide (DU-717) in plasma using electron-capture gas chromatography.

A gas chromatographic method has been developed which enables accurate determination of a new antihypertensive agent, DU-717, in plasma. DU-717 is first extracted with ethyl acetate and, after a clean-up procedure, derivatized with peracetic acid followed by diazomethane to form 2-methyl DU-717 N-oxide (direct methylation leads to mixtures). The N-oxide is then pyrolyzed to 2-methyl DU-717 on a gas chromatograph equipped with electron-capture detection. Accurate determinations are possible over a concentration range from 10 to 150 ng/ml of DU-717 in plasma at a relative standard deviation of 6.2%. The minimum detectable concentration is 1 ng/ml. Plasma levels of DU-717 in spontaneously hypertensive and normotensive rats following single oral administrations (10 mg/kg) have also been determined.

Administration, Oral↗
PubMed1978

Determination of 1,2-benzisoxazole-3-acetamidoxime hydrochloride (PE-257) in plasma using electron-capture gas chromatography.

A gas chromatographic method has been developed that permits the accurate and specific determination of a new psychotropic agent, PF-257, in plasma. PF-257 is extracted with ethyl acetate from alkaline plasma and, after a clean-up procedure, derivatized with heptafluorobutyric anhydride to form 3-[(5-n-heptafluoropropyl-1,2, 4-oxadiazol-3-yl)methyl]-1,2-benzisoxazole (HOMB). The HOMB is assayed on a gas chromatograph equipped with an electron-capture detector. Accurate determinations of PF-257 are possible in the concentration range from 1-40 ng/ml with a relative standard deviation of 6.8%. The minimum detectable concentration in plasma is 0.1 ng/ml. Plasma levels of PF-257 in rats receiving intravenous or oral dosing (10 mg/kg) were determined.

Animals↗
PubMedDate not supplied

Studies on disposition and metabolism of tolmetin, a new anti-inflammatory agent, in rats and mice. II. Urinary metabolites.

A new urinary metabolite of tolmetin was found in rat urine and identified as the hydroxymethyl metabolite (tolmetin-OH), an intermediate in the formation of the known carboxy metabolite (tolmetin-COOH). In rats of two strains, the following percentages of the urinary reactivity of [14Ia1tolmetin were found in 24 hr: unchanged tolmetin-COOH (58--60%), tolmetin-OH (18--24 %), and its conjugate 6--14%. Mouse urine contained the unchanged drug (about 20%), its conjugate and tolmetin-COOH (60%). Similarly to mouse urine, human urine contained negligible amounts of tolmetin-OH.

Animals↗