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T Inaba

Publications and source records attributed to T Inaba.

At least 451 records · Page 25Linked to original sources
PubMed1978

Effects of anesthetics on diphenylhydantoin metabolism in the rat: possible inhibition by diethyl ether.

The effects of diethyl ether and urethane on the elimination of diphenylhydantoin (DPH) in the rat were compared. The apparent half-life of DPH following a dose of 10 mg/kg, iv, under continuous ether anesthesia was 284 +/- 47 min, while the half-life under urethane anesthesia was 25.5 +/- 6.3 min. The latter was in agreement with the literature value for DPH half-life without anesthesia. The effects of both anesthetic agents on bile flow and indocyanine green clearance were not different. Following intravenous administration of DPH (1 mg/kg), DPH metabolites excreted in bile at 2 h were 75.3 +/- 4.8% of the dose with urethane anesthesia and 25.0 +/- 5.0% of the dose with continuous ether anesthesia. The data suggest that ether may inhibit the DPH metabolism in vivo, most likely at the hydroxylation step, while urethane does not.

Anesthetics↗
PubMed1977

A case of deficiency of N-hydroxylation of amobarbital.

It has been shown recently that the overall metabolism of amobarbital in man is essentially under genetic control. The drug normally undergoes two hydroxylation reactions, leading to 3'-hydroxyamobarbital (C-OH) and N-hydroxyamobarbital (N-OH). This paper describes a sibship in which two mothers who are identical twins show a gross deficiency on N-OH elimination in urine. The whole set of sibship data suggests that this deficiency represents a recessive trait controlled by a single pair of allelic autosomal genes which regulate N-OH formation. Several methodical approaches to assess an individual's capacity for N-OH formation are illustrated. There was no evidence of compensatory or concordant regulation of the two hydroxylation reactions. The case of this family illustrates that the functional lack of a biotransformation reaction is almost certain to be overlooked if one measures only the disappearance of a multimetabolized drug and not the appearance of metabolites.

Adolescent↗
PubMed1977

Metabolism of flurazepam by the small intestine.

The metabolism of flurazepam-5-14C has been studied in man following catheterization of the portal and hepatic veins. Flurazepam was administered through a tube into the stomach in one patient and into the duodenum in two patients. Thin-layer chromatographs of portal vein blood showed that there was a rapid and early appearance of metabolites of flurazepam consistent with the metabolism of the flurazepam by the intestinal mucosa and at times when the concentrations in the hepatic vein and peripheral blood were very much lower than those in the portal vein. The major metabolites identified in portal vein blood were the mono- and didesetyl metabolies of flurazepam. Considerable hepatic uptake of flurazepam and its metabolites occurred, as evidenced by the lower concentrations of the parent compound and metabolites in the hepatic vein. Thus, "first-pass" metabolism of flurazepam following oral administration occurs in the small bowel mucosa of man as well as in the liver.

Adult↗
PubMed1976

Biliary elimination of diazepam in man.

The metabolism of 14C-5-diazepam has been studied in 5 patients with T tube biliary drainage. A single bolus of 40 to 50 muCi was given intravenously and blood, urine, and bile were analyzed from 5 to 14 days. The mean half-life of elimination from blood was 93.2 hr; the major metabolite noted in blood was N-desmethyl-diazepam. In urine the average recovery of radioactivity was 48.9% and consisted of 3 OH-diazepam, 4'OH-diazepam, and oxazepam. In bile the average recovery of radioactivity was 5.35% (corrected to a bile flow of 700 ml was 15.0%) and consisted of the same metabolites as in the urine. Essentially no diazepam or N-desmethyl-diazepam was found, and therefore an enterohepatic circulation cannot be held to account for the prolonged half-life of these substances in man.

Adult↗
PubMed1976

Disposition kinetics of two oral forms of quinidine.

There are relatively few studies on the disposition properties of quinidine. We have studied in 10 normal subjects conventional quinidine sulfate and a slow-release quinidine bisulfate. Single and repetitive doses were given; blood and urine concentrations were measured by the method of Cramer and Isaakson. After a single dose of two tablets of quinidine sulfate (400 mg), the average peak concentration was 2.13 +/-0.22 mug/ml (+/-SEM); following two tablets of the slow-release form, the average peak concentration was 1.17 +/-0.12 mug/ml. T-max was approximately 2 hr with quinidine sulfate and 4 hr with quinidine bisulfate. One fourth of both forms of the drug was recovered in the urine. Total body clearance was 0.36 L/kg-hr and renal clearance was 117 +/-22ml/min for both. With multiple dosing the serum quinidine concentration was higher than these predicted from the results of the single-dose study. Based on the mean estimates of quinidine half-life of 6 hr, a rapid method for achieving steady-state levels of quinidine would be to give an initial dose twice that of the maintenance dose. With the slow-release product if an equivalent dose was given every 12 hr, the mean steady-state quinidine serum concentration would be approximately the same.

Adult↗
PubMed1976

Amobarbital--a probe of hepatic drug oxidation in man.

Some aspects of the fate of amobarbital were investigated since this drug is being used as a probe to gauge drug oxidation in man. The mean ratio of orally available over intravenously injected amobarbital was established as 0.99 +/- 0.11 (SD), by comparing integrated concentration-time curves, indicating complete absorption and absence of a first-pass effect. One subject ingested 200 mg of amobarbital sodium, and amobarbital concentrations in serum were monitored for 5 days thereafter. Elimination of amobarbital under these conditions followed first-order kinetics. One subject ingested amobarbital 7 times over a period of 3 yr; plasma clearances (32.1 +/- 1.8 [SD]ml/min) exhibited remarkable constancy, while biologic half-lives (26.5 +/- 3.1 hr) and distribution volumes (73.6 +/- 8.0 L) showed some fluctuation. The distribution of parameters of amobarbital elimination was investigated in 36 unrelated subjects. Amobarbital half-lives (23.8 +/- 6.7 hr) appeared to be normally distributed, while the clearances (36.7 +/- 10.0 ml/min) might not follow a normal distribution.

Adolescent↗
PubMed1976

Genetic study of amobarbital elimination based on its kinetics in twins.

Following the intravenous administration of 125 mg amobarbital sodium in 7 pairs of dizygotic and 7 pairs of monozygotic twins, the time-course of plasma concentrations was observed. The number of detectable compartments varied from subject to subject but was consistently 1 or 2 or 3 within a given individual. The terminal slope of the semilogarithmic concentration-time plot (corresponding to biologic half-life of 22.8 hr) did not represent the elimination rate constant even in persons with apparently single-compartmental characteristics. The redistribution of amobarbital was rapid in comparison with its elimination. The rate of the latter (characterized by kel = 0.051 hr-1, plasma clearance = 37.7 ml/min) could be closely identified with the rate of metabolism. The twin data showed that genetic control was exerted on kinetic parameters characterizing the rate of amobarbital elimination and, therfore, the rate of its metabolism. Correlation analysis suggested that this control was independent of size factors, which were themselves substantially heritable. The genetic analysis of twin data included, in addition to intracelass correlations and Holzinger's H factors, newly developed lower (and upper) bounds of the broad-sense heritability. In pharmacogenetic studies, assessment of model-independent kinetic parameters, such as plasma clearance with or without adjustment for body weight, is recommended.

Administration, Oral↗
PubMed1975

Comparative drug elimination in man-diphenylhydantoin and amobarbital.

The concentration of 5,5-diphenylhydantoin (DPH) in serum was determined at selected time intervals in seven healthy male volunteers starting 10 h after an oral dose of 400 mg sodium DPH was given. The data were analyzed according to a one-compartment model assuming first-order kinetics. The mean serum half-life was 19.28 h +/- 5.87 (SD). A positive correlation coefficient (r=0.84, p less than 0.05) was found between the serum DPH half-life and the serum amobarbital half-life in the seven subjects. The urinary levels of free plus conjugated 5-(p-hydroxyphenyl)-5-phenyl-hydantoin were determined for 12 h periods over a minimum of two days following the 400 mg oral dose of sodium DPH. Subjects with a short DPH half-life tended to excrete in urine a greater amount of p-HPPH as compared to subjects with a long DPH half-life. In the case of one subject, the urinary excretion of p-HPPH plateaued five days after DPH administration and the apparent elimination half-life determined from the p-HPPH urinary excretion data was 19.16 h as compared to the value of 19.53 h calculated from the DPH serum levels.

Adult↗