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T Inaba

Publications and source records attributed to T Inaba.

At least 433 records · Page 24Linked to original sources
PubMed1981

Antipyrine metabolites in two populations.

After ingestion of 1 g antipyrine by healthy subjects of either Caucasian (n = 32) or Oriental (n = 18) background, urine was collected for 48 hr. and three major metabolites of antipyrine were determined. 21.8 +/- 1.1 (S.E.)% of the dose was excreted as 4-hydroxyantipyrine (4OHA), 12.7 +/- 0.6% as norantipyrine (NORA) and 5.9 +/- 0.3% as 3-hydroxy-methylantipyrine (3HMA). Oriental and Caucasian subjects showed similar mean recovery of each metabolite. The range of variation (F-test) of metabolite excretions between the 2 groups was again similar except for 3HMA which showed greater variation (p less than 0.01) in Orientals than in Caucasians. The fundamental similarity in antipyrine metabolism in the two populations is remarkable, because metabolite patterns of antipyrine differed significantly between subjects, and because the same two populations are known to differ much in their capacity for other drug oxidations.

Adult↗
PubMed1981

Identification of p(4')-hydroxyantipyrine as a metabolite of antipyrine in man.

Several metabolites of antipyrine have been known for many years, but their recovery does not fully account for the drug in man. During the development of a HPLC assay of 3-hydroxymethylantipyrine, a major metabolite of antipyrine, the presence of another metabolite was noted. Its structure was postulated to be p(4')-hydroxyantipyrine (pOHA) on the basis of chemical derivatization and of mass spectrometry. The structure was confirmed by physicochemical comparison with a synthetic compound. The amount of pOHA in man is small, representing about 2-4% of the dose and less than 1% in the rat.

Acetylation↗
PubMed1981

[Analysis of RIA standard curve by log-logistic and cubic log-logit models (author's transl)].

In order to improve goodness-of-fit in RIA standard analysis, programs for computing log-logistic and cubic log-logit were written in BASIC using personal computer P-6060 (Olivetti). Iterative least square method of Taylor series was applied for non-linear estimation of logistic and log-logistic. Here "log-logistic" represents Y = (a--d)/(1+log(X)/c)b)+d As weights either 1, 1/var(Y) or 1/sigma 2 were used in logistic or log-logistic and either Y2(1--Y)2, Y2(1-Y)2/var(Y), or Y2(1--Y)2/sigma 2 were used in logistic or log-logistic and either Y2(1--Y)2, Y2(1--Y)2/var(Y), or Y2(1--Y)2/sigma 2 were used in quadratic or cubic log-logit. The term var(Y) represents squares of pure error and sigma 2 represents estimated variance calculated using a following equation log(sigma 2 + 1) = log(A)+J log(y). As indicators for goodness-of-fit, MSL/Se2, CMD% and WRV (see text) were used. Better regression was obtained in case of alpha-fetoprotein by log-logistic than by logistic. Cortisol standard curve was much better fitted with cubic log-logit than quadratic log-logit. Predicted precision of AFP standard curve was below 5% in log-logistic instead of 8% in logistic analysis. Predicted precision obtained using cubic log-logit was about five times lower than that with quadratic log-logit. Importance of selecting good models in RIA data processing was stressed in conjunction with intrinsic precision of radioimmunoassay system indicated by predicted precision.

Computers↗
PubMed1980

Deficient metabolism of debrisoquine and sparteine.

Genetic deficiencies of alicyclic hydroxylation of debrisoquine and of sparteine oxidation are independently discovered entities, each of clinical significance in its sphere. This paper reports evidence to indicate that these 2 deficiencies have the same cause. Previous investigation of one of the affected subjects had revealed normal oxidative metabolism of amobarbital and antipyrine in terms of both metabolic rates and urinary metabolite patterns. Thus the genetic defect in the metabolism of sparteine and debrisoquine is not a generalized deficiency of drug oxidation or of the cytochrome P450 system.

Amobarbital↗
PubMed1979

Cocaine metabolism: cocaine and norcocaine hydrolysis by liver and serum esterases.

The hydrolysis of cocaine and its N-demethylated product, norcocaine, by esterases was examined in liver and serum. Both liver and serum enzymatically formed ecgonine methyl ester from cocaine. The liver enzyme had a much lower affinity for cocaine than that of serum, indicating that a different form of esterase was present in liver. The liver enzyme had a similar affinity for both norcocaine and cocaine. Likewise, the serum enzyme showed similar affinities for both substrates. The Vmax estimates, however, were consistently higher for norcocaine than cocaine in both liver and serum. Benzoyl ecgonine, a major metabolite of cocaine formed by hydrolysis, was not produced enzymatically in either serum or liver; the rate of spontaneous formation at physiological pH suggests that this metabolite may arise nonenzymatically in the body.

Carboxylic Ester Hydrolases↗
PubMed1979

Radioimmunoassay of serum and ovarian pregnenolone in immature rats.

Antiserum was generated in a rabbit against pregnenolone-16 alpha-carboxyethyl thioether conjugated to bovine serum albumin. The antibody, used for the assay of pregnenolone in extracts of serum and tissue homogenates, proved sufficiently specific to allow direct assay of extracts without chromatography. Sensitivity, defined as that point on the standard inhibition curve equal to the lower value 2 SD from the mean radioactivity bound to antibody in the buffer control (zero hormone) tubes, was 0.02 ng. The accuracy was confirmed by the recovery of known amounts of pregnenolone added to serum and aqueous buffer medium. The inter- and intra-assay coefficients of variation were respectively 10.6% and 9.1%. Specificity was confirmed by checking cross reactivity of various steroids and by finding comparable pregnenolone levels in samples before and after chromatography. The administration of aminoglutethimide to rats resulted in the reduction of ovarian and serum pregnenolone levels. Administration of isoxazole, on the other hand, caused an increase in both serum and tissue pregnenolone levels. These findings are in agreement with accepted views of the action of these two metabolic blocking agents.

Animals↗
PubMed1979

Preferential binding of radiolabeled zearalenone to a protein fraction of Fusarium roseum graminearum.

Zearalenone [6-(10-hydroxy-6-oxo-trans-1-undecenyl)beta-resorcyclic acid lactone] is a hormone produced by Fusarium spp. which regulates the sexual stage in F. roseum. 3H- and 14C-labeled zearalenone were found to bind preferentially to one of two peaks containing uncharacterized proteins obtained from the cytosol of young mycelium and resolved by gel column chromatography. The proteins were partially purified by successive resolution on Sephadex G-100, Sephadex G-200, and BioGel P-300. Free zearalenone (37%) was reisolated from the purified proteins after resolution by thin-layer chromatography or partitioning with ethyl acetate.

Fungal Proteins↗
PubMed1979

Phenacetin concentrations in portal and hepatic venous blood in man.

After intra-gastric or intra-duodenal administration of phenacetin (200 mg in solution), concentrations of phenacetin and its 0-dealkylated metabolite, acetaminophen, in portal and hepatic veins and in peripheral blood were monitored. A sharp increase in the portal concentration of phenacetin indicated rapid absorption. The concentration ratio of acetaminophen to phenacetin in early portal blood was 0.01--0.11 and lower than the ratio in hepatic vein. The hepatic extraction ratio of phenacetin was calculated to be 0.59--0.78. It is concluded that 0-dealkylation occurs mainly in the liver and only to a limited extent in the gastrointestinal wall.

Acetaminophen↗
PubMed1978

Metabolism of cocaine in man.

Following ingestion of [N-14CH3]cocaine (10 mg, 2.3 muCi) by 2 healthy subjects, breath, saliva, serum, and urine samples were collected serially. Labeled CO2 production was monitored as a measure of N-demethylation of cocaine. The cumulative excretion of 14CO2 in 5 hr was 2.4% and 6.2% of the administered dose with half-lives of 2.3 and 1.4 hr, respectively. The greater N-demethylation was found in a subject with lower plasma cholinesterase activity. Radioactivity excreted in 0 to 28 hr urine reached 65% to 75% of the dose. Ecgonine methyl ester, a product of cocaine hydrolysis by plasma cholinesterase, was identified as a major metabolite in the urine of both subjects and accounted for 32% to 49% of the urinary metabolites.

Adult↗
PubMed1978

Distinctive patterns of amobarbital metabolites.

This paper establishes that the relative proportion of amobarbital metabolites in urine is highly variable from person to person and that observations of plasma half-life give no indication of this variability, but it shows that a valid estimate of a given person's metabolite pattern can be obtained by studying a single urine specimen in the postdistributive phase. The two metabolites which were measured in urine accounted on the average of 9 subjects for 80% +/- 3% of the dose with a range from 66% to 94%. The two metabolites were the well known 3'-hydroxyamobarbital (COH) as a product of side chain hydroxylation and N-beta-D-glucopyranosyl amobarbital (N-glu), a glucose conjugate which at some earlier time had been mistaken for an N-hydroxylation product. Among 129 volunteer subjects, the metabolite ratio N-glu/COH showed a median value of about 0.5 with a range from 0 to 2.8. A virtual absence of N-glu was observed in one of the 129 subjects and confirmed by a second administration of amobarbital 3 mo later. Of the 14 subjects with predominant N-glu excretion 4 were of Chinese origin, while there were 6 Chinese among the 115 other subjects (p less than 0.02).

Amobarbital↗
PubMed1978

Enzyme induction following a single dose of amobarbital in dogs.

The elimination of amobarbital in dogs was investigated by injecting various doses of amobarbital into a given animal. At low doses (3 mg/kg) serum levels declined in a first-order fashion. Superficially, at high doses (20 mg/kg) the relationship between serum concentration and time could be quantitatively characterized by simple one-compartment saturable kinetics. Indeed, qualitatively, saturation of the amobarbital-metabolizing enzymes was indicated by a shallower initial slope of the semilogarithmic concentration--time profile at the high than at the low dose. However, in addition, an acute enzyme induction phenomenon was observed which was indicated by a shorter terminal half-life of amobarbital at the high dose than after the low dose and also by a shortening in antipyrine half-life.

Amobarbital↗