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N Aoyagi

Publications and source records attributed to N Aoyagi.

104 records · Page 6Linked to original sources
PubMed1982

Correlation of the bioavailability of diazepam from uncoated tablets in beagle dogs with its dissolution rate and bioavailability in humans.

The bioavailability of diazepam (I) in uncoated tablets in beagles was tested using tablets tested previously in humans. The correlations of the dissolution rates and bioavailabilities of these tablets in humans and beagles were examined. The plasma level of N-desmethyldiazepam (II), the main metabolite of I, was used as an index of bioavailability after p.o. administration of uncoated tablets of I, because I is rapidly metabolized. Thus the plasma level of I is very low, and AUCs (areas under plasma level-time curves) calculated from plasma levels of II were related to the dose of I (2-10 mg). With different tablets, the rates and extents of bioavailability of I differed significantly in beagles, but only the rate of bioavailability showed significant differences in humans. The rank orders of tablets, based on the blood levels of II soon after p.o. administration of the tablets were the same, but other parameters of bioavailability of I in the tablets were quite different in beagles and humans. Consequently, there was no significant correlation between the bioavailabilities of I in beagles and humans. The gastric fluid of beagles is almost neutral, and the bioavailabilities of the tablets in beagles correlated well with the dissolution rates of I determined at pH 4.6, but not at pH 1.2. The differences in the bioavailabilities of I in humans and beagles were attributed to differences in transit time in the gastrointestinal tract and/or in the volume of the gastrointestinal fluid.

Animals↗
PubMed1982

The bioavailability of diazepam from uncoated tablets in humans--Part I: correlation with the dissolution rates of the tablets.

Dissolution studies of 15 preparations of commercial uncoated tablets of diazepam (5 mg) were performed by six methods (beaker, rotating basket, oscillating basket, solubility simulator, rotating flask, and single basket). Diazepam dissolved rapidly at pH 1.2; the T50 (the time of 50% dissolution) values were less than 5 min. But at pH 4.6, T50 estimated by rotating basket method lasted 3-120 min. Four different tablets of diazepam were chosen for the bioavailability tests in humans. The bioavailabilities of the four tablet preparations were estimated by serum level measurements after a single dose to 12 adult male volunteers. Statistical analysis of the data showed significant differences in the rate of bioavailability (peak concentrations and serum concentrations at 1, 2, and 3 h after administration), but not in the amount of available (AUC). The mean peak concentration and serum concentration at 1 h showed significant correlation with T50 and T70 determined by the rotating flask method at pH 4.6 in log-log regression. The peak concentration and serum concentration at 1 h were also correlated with T70 determined by the rotating flask method at pH 4.6 and T70 determined by the rotating basket method at pH 4.6 on normal-normal regression. In contrast, the dissolution rates determined at pH 1.2 did not show a good correlation with in vitro parameters.

Adult↗
PubMed1982

The bioavailability of diazepam from uncoated tablets in humans--Part II: effect of gastric fluid acidity.

The healthy male volunteers participating in bioavailability tests of diazepam tablets were classified into two groups, high and low acidity groups, on the basis of the acidity of their gastric fluid. This was estimated by the Gastrotest method. The bioavailability parameters of four tablet preparations of diazepam (5 mg) after single administration were compared statistically between the two groups. Subjects with low acidity showed significantly lower diazepam serum levels than subjects with high acidity at 1 and/or 2 h after administration of tablets B, C, and D, which showed slower rates of dissolution at pH 4.6. Tablet B gave a significantly lower peak concentration than the other tablets in the high acidity group, whereas in the low acidity group tablet A gave a higher level than the other tablets. The peak concentration in the low acidity group correlated well with the dissolution rates represented as 1/T70 (time of 70% dissolution) at pH 4.6, but we could not find a good method for determining the dissolution rates except for T50 values with the rotating flask method at pH 4.6; these values significantly correlated with the peak concentrations of the high acidity group. From our results we conclude that the acidity of the gastric fluid affects the bioavailability of a drug such as diazepam, which has a pH-dependent dissolution rate and an especially slow rate of dissolution at pH 3-7.

Adult↗
PubMed1982

[Compliance of brain--Part 2 Approach from the local elastic and viscous moduli (author's transl)].

It is important to have information about physical property of the brain in order to elucidate both the physical changes of the morbid brain and the physical mechanism of the traumatic brain injury. Under the hypothesis that reaction of the active brain to the dynamic load can be compared to the Maxwell-Voigt three dimensional model, elastic property of the brain was obtained as the Young's modulus (E: 10(-2) Kgf/cm2) of which error was less than 10%, and viscous property of the brain as the Viscous modulus (eta: 10(-2) Kgf.sec/cm2). And it was confirmed that the reactive pressure of the brain to dynamic load came from the surface to about 15 mm depth of the brain. In this report, experiments were done on the alive normal brains, the edematous ones nd necrotic ones which were produced by the cold injury (dry ice-aceton) in dogs (9.0--16.0 Kg). In the normal brain, E = 3.24 +/- 0.25, eta = 1.10 +/- 0.37 and these moduli were also stable when the physical conditions of the brain were stable. Under the dehydration by 20% mannitol, E increased in its value (p less than 0.01). But under the hydration by 5% glucose, E did not change at all. In the edematous brain, E = 3.28 +/- 0.44, eta = 1.74 +/- 0.06 and E of the edematous brain was almost same as that of normal ones, but under the dehydration, E of the edematous brain decreased (p less than 0.10), on the other hand it increased in its value under the hydration (p less than 0.05). In the necrotic brain, E = 1.60 +/- 0.14, eta = 0.82 +/- 0.28. Both moduli were of lower values and moreover they did not change its values at all under dehydration and hydration. As Young's modulus is the elastic index of the brain, the converse (1/E) should be compliance of the brain, that is to say, buffer effect of the brain. As for the compliance, the necrotic brain has maximum buffer effect and the over-hydrated edematous brain and the dehydrated normal ones have minimum buffer effect. From analysing the changes of the viscous moduli, it became clear that the viscous moduli took quite different functions in alive brains and in fatal ones, and it was suspected that the alive brain might not be so simple in its viscoelastic property.

Animals↗
PubMed1981

The bioavailabilities of aspirin from an aspirin aluminum and an aspirin tablet and the effects of food and aluminum hydroxide gel.

The bioavailability of aspirin from an aspirin aluminum tablet was compared with that from an aspirin tablet in humans by determining total salicylate excreted in the urine. The effects of concomitant intakes of antacid or food on the bioavailability of aspirin were also investigated. The bioavailability of aspirin from an aspirin aluminum tablet was nearly 60% of that from an aspirin tablet. The low bioavailability of aspirin from an aspirin aluminum tablet was caused by slow release of aspirin from the aluminum complex, and not increased by concomitant intake of food. Intake of food, however, reduced both rate and extent of bioavailability of aspirin from an aspirin tablet, but dried aluminum hydroxide gel granules had no effect on the bioavailability of it.

Adult↗
PubMed1976

[Experience with radio isotope myelography from neurosurgical aspects (author's transl)].

Experience with Radio Isotope Myelography is reported here. 169Yb-DTPA as a tracer was intrathecally injected at lumbar region in twenty three patients with various spinal cord lesions. The first scanning is perfomed after comfirming by gamma-camera that the tracer reaches to the lesion, the second and the third scannings are done according to the ascending rate of the tracer. (I) Normal scintimyelogram (A) In normal case, the shape of the Radio Isotope Myelogram well corresponds the shape of anatomical subarachnoid space. (B) In normal adult cases, the tracer comes up to the cisterna magna in 20-25 minutes after the lumbar injection. Therefore, the scintimyelographic diagnosis should be made not only by the shape but also by the ascending rapidity of the tracer. (II) Abnormal scintimyelogram Abnormal scintimyelograms could be summarized as following three categories. (A) "Delay": It means delay of the ascending of the tracer. Besides, "Transient delay" found in a case of Arnord-Chiari's malformation was proposed. (B) "Partial block": It meas a defect at the level of the lesion. This "Partial block" were observed in cases of spinal cord angioma, cervical spondylosis and spinal cord tumor etc. (C) "Complete block": It means the stagnation of the tracer below the lesion. To sum up, Rario Isotope Myelography, especially in partial block, can more easily and more sensitively represent the maximum extent of the spinal cord lesion than other myelographic study or angiographic one. On the other hand, we can not qualitatively diagnose about the lesions by its indistinct border.

Adolescent↗
PubMedDate not supplied

Japanese guidance on bioavailability and bioequivalence.

The guideline of bioequivalence tests for generic drugs in our country was recently revised (1), and guidelines for formulation change and different strengths were published in February 2000. This paper describes those guidelines briefly.

Biological Availability↗