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Biomedical subjects

N Kaniwa

Publications and source records attributed to N Kaniwa.

43 records · Page 3Linked to original sources
PubMed1982

Effect of food on the bioavailability of griseofulvin from microsize and PEG ultramicrosize (GRIS-PEG) plain tablets.

Effect of food on the bioavailability of griseofulvin from its two plain tablets, a commercial microsize product and a PEG ultramicrosize (GRIS-PEGR) one, was investigated. The drug was dissolved at a slower rate from ultramicrosize formulation than from microsize one in 18 1 of pH 7.2 buffer but at a little faster rate in 40% dimethylformamide. When administered to fasting subjects, the microsize product showed higher serum levels and peak serum level than ultramicrosize one but the extent of the bioavailability was nearly the same. A standard breakfast enhanced the rate of absorption of the drug from both the products, especially from ultramicrosize one, and those products were equivalent in the rate and extent of bioavailability after food ingestion. The peak serum level of ultramicrosize product in nonfasting was about twice higher than that in fasting subjects. The different intensities of food effect on the bioavailabilities from two dosage forms suggest that formulation factors should be considered for the evaluation of food effect.

Adult↗
PubMed1982

The bioavailability of flufenamic acid from aluminum flufenamate tablet and flufenamic acid capsule, and the influence of food and aluminum hydroxide gel.

The bioavailabilities of flufenamic acid (I) from a commercial aluminum flufenamate (II) tablet and I capsule were estimated by measuring urinary excretion of I and its metabolites fluorometrically. The dissolution rates of I from both dosage forms were also determined. The effects of concomitant intake of food or antacid on the bioavailabilities from the II tablet and the I capsule were investigated. The extent on I bioavailability from the II tablet was less than 30% of that from the I capsule. Dissolution tests suggested that the low bioavailability of I from II tablet resulted from the extremely slow release of I from the II complex. Intake of a standard meal retarded I absorption from I capsule, but did not affect that from the II tablet. Ingestion of dried aluminum hydroxide gel granules had little effect on I bioavailability from the I capsule.

Adult↗
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↗
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↗