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Biomedical subjects

N Kaniwa

Publications and source records attributed to N Kaniwa.

At least 19 recordsLinked to original sources
PubMed1998

Accumulation, Metabolism, and Depuration of Organotin Compounds in the Marine Mussels Mytilus graynus and Mytilus edulis under Natural Conditions.

The accumulation, transformation, and depuration of tri-n-butyltin (TBT) were studied over periods of approximately 60-70 days using marine mussels, Mytilus graynus and Mytilus edulis, under natural conditions. M. graynus collected at a lightly polluted site were transplanted to a highly polluted site and M. edulis collected at a highly polluted site were transplanted to a lightly polluted site. TBT taken up in M. graynus showed a bioconcentration factor of 10 500 in the accumulation phase. Di-n-butyl(3-oxobutyl)tin, which is a main metabolite of TBT in M. edulis, showed a longer half-life (8.13 days) than that of the parent compound (4.82 days) in the depuration phase. On the other hand, another metabolite, di-n-butyl(3-hydroxybutyl)tin, showed a shorter half-life (3.98 days) than that of the parent compound. The different half-lives among TBT and its metabolites are responsible for the different metabolic patterns in blue mussels at each sampling time.

Journal Article↗
PubMed1998

[Validation of dissolution testing: evaluation of vibration levels of dissolution apparatuses].

The collaborative study participated by seven laboratories was carried out to develop a dissolution standard for evaluating vibration levels of dissolution apparatuses using enteric-coated granules of cefalexin (EG). Dissolution apparatuses could be divided into two groups according to their vibration levels and the dissolution test results of EG by the rotating basket method at 50 rpm. The critical value of acceleration was about 0.05 m/s2. The upper limit of normal dissolution rates of EG was calculated from the results of the rotating basket method at 50 rpm obtained from low vibration apparatuses. All high vibration apparatuses used in this study were distinguished by the limit from low vibration apparatuses, although most of them were not distinguished by current USP calibrators. These results suggest that EG would be useful as a calibrator for detection of apparatuses on high vibration levels.

Calibration↗
PubMed1993

[Analytical validation in compendium methods].

Well validated analytical methods should be used in official tests in order to eliminate the type I and II errors. The analytical validation is the process to confirm that the performance characteristics of a proposed analytical method is adequate for its intended use. The performance characteristics of an analytical method are validated by evaluating that observed analytical performance parameters of the analytical method meet the criteria required by a test to which the analytical method is applied. Basic rules in analytical validation were described in this report. The more strict rules for determination of the limit of detection and the test of precision than usually applied were proposed.

Chemistry Techniques, Analytical↗
PubMed1992

Gastric emptying of tablets and granules in humans, dogs, pigs, and stomach-emptying-controlled rabbits.

Rates of gastric emptying of nondigestible tablets and granules in humans were compared with those in three animal models: dogs, minipigs, and stomach-emptying-controlled rabbits. The rates of gastric emptying of both dosage forms in dogs tended to be faster than or similar to those in humans, whereas the rates in pigs were slower. In stomach-emptying-controlled rabbits, no tablets were emptied from the stomach because of their large size. The rate of gastric emptying of granules in rabbits was slow and variable. Food delayed gastric emptying in dogs, especially for tablets. In rabbits, the rate of gastric emptying of granules was faster when the granules were given before feeding, in comparison with that after feeding or under fasting conditions. We concluded that the dog is a better animal model for bioavailability studies under fasting conditions than the pig and the rabbit.

Adult↗
PubMed1992

Gastric emptying rate of drug preparations. III. Effects of size of enteric micro-capsules with mean diameters ranging from 0.1 to 1.1 mm in man.

The gastric emptying rates of three enteric micro-capsule preparations with mean diameters of 1.1 mm and less (1.1, 0.5 and 0.1 mm) were compared. The gastric emptying rate was evaluated by determining the pharmacokinetic parameters of pyridoxic acid, including Vmax (peak excretion rate) and Tmax (time to reach peak excretion rate) after oral administration of micro-capsules containing pyridoxal phosphate as a marker drug to five healthy subjects. When given under fasting conditions, the gastric emptying rates of these preparations, according to Tmax, differed significantly; the preparations with smaller particle sizes were emptied from the stomach at a faster rate than those with larger particle sizes. However, under non-fasting conditions the gastric emptying rates were virtually the same, regardless of particle size, and all the preparations were emptied from the stomach at a much slower rate than when administered under fasting conditions.

Adult↗
PubMed1991

Effect of food on the bioavailability of cyclandelate from commercial capsules.

The bioavailability of five capsules of cyclandelate that are commercially available in Japan was determined in ten healthy volunteers by measuring mandelic acid (a main metabolite of cyclandelate) excreted in the urine. Bioinequivalence among the five capsules was demonstrated. The relative cumulative excretion of mandelic acid of the most poorly bioavailable capsule was 38% of the most highly bioavailable capsule. The effect of food on the bioavailability of these two capsules was investigated by use of two different kinds of food, one containing fat and one containing high carbohydrates but very low fat. The bioavailability of the two capsules was increased when subjects consumed both types of food before drug administration, although there was a greater effect on bioavailability with food containing fat. This suggests that the absorption of cyclandelate was incomplete in fasting subjects, even from the capsule with the highest bioavailability. Bioinequivalence between the two capsules remained after postprandial drug administration.

Administration, Oral↗
PubMed1991

Bioavailability of cyclandelate from capsules in beagle dogs and dissolution rate: correlations with bioavailability in humans.

The bioavailability in beagle dogs and the dissolution rates of cyclandelate from five capsule preparations commercially available in Japan were measured. One of the capsules that showed an extremely low bioavailability in humans also showed the lowest bioavailability in beagle dogs, although the difference in bioavailability with the highest preparation was smaller than in humans. A significant correlation was obtained between the results of the studies in humans and beagles. However, the power of the test using beagles was extremely low in comparison with that in the human study. Food enhanced the bioavailability of cyclandelate from the capsules having the highest and lowest bioavailability in the fasted state in beagles as observed in the human study previously. The bioinequivalence of the cyclandelate capsules detected in the fasted state disappeared in the fed state in the beagle dog study, while the bioinequivalence still remained in the non-fasted state in human subjects. Thus bioequivalence testing in the fed state led to different results in both species. The most poorly bioavailable capsule in both species in the fasted state showed a slow dissolution rate by several dissolution methods with moderate stirring. In order to obtain a good correlation with in vivo bioavailability, a large volume of test solution and addition of Tween 80 were required. Extensive growth of whiskers (needle-like crystals) was observed in the entire capsule mass having the lowest bioavailability.

Animals↗
PubMed1990

Application of the NONMEM method to evaluation of the bioavailability of drug products.

The NONMEM method, one of the methods used for analysis of population pharmacokinetics, was applied to the evaluation of the relative bioavailability of drug products. The data of 2 x 2 crossover studies of several drugs and a 3 x 3 crossover study of phenytoin using healthy volunteers were analyzed by the NONMEM method, as well as by the confidence interval procedure, which is a standard approach to the bioequivalence test data using model-independent parameters. Very close confidence intervals for the relative difference in bioavailability were estimated by the NONMEM method and the standard approach, both in cases where products were bioequivalent and where they were not. The NONMEM method could also correctly estimate the relative bioavailability of the products using simulated clinical data obtained by randomly reducing the sampling points of the phenytoin data mentioned above, which cannot be analyzed by the standard approach. Thus, the usefulness of the NONMEM method was confirmed for evaluation of bioavailability using clinical or experimental data.

Administration, Oral↗
PubMed1990

Effects of food on bioavailability of two indomethacin capsules containing different sizes of particles.

Two different indomethacin capsules, a commercial one containing fine drug particles and an experimental capsule containing 125-177 microns particles, were employed in this study. The commercial preparation showed faster in vitro dissolution than the experimental one. When administered to humans having normal acidity of the gastric juices, the commercial capsule exhibited higher Cmax and smaller Tmax and mean residence time (MRT) than the experimental one both in fasting and nonfasting states, although the two capsules were equivalent in area under the serum concentration-time curve (AUC). The ingestion of a breakfast delayed the gastrointestinal absorption from both preparations, which resulted in larger Tmax's and MRT's and smaller Cmax's in the nonfasting state. Food, however, did not have any significant effect on the AUC's of the preparations.

Adult↗
PubMed1989

Power analyses of moment analysis parameter in bioequivalence tests.

Simulated and experimental data were used to evaluate the mean residence time (MRT) as a parameter for estimating the rate of bioavailability in bioequivalence tests and to compare MRT with tmax (the time of peak drug concentration), both pharmaceutically and statistically. Although the values of MRT were more dependent on the elimination rate constant than tmax, MRTs were sufficiently sensitive to variations in the absorption rate. The statistical power of MRT infinity obtained by an extrapolation method was lower (especially when the flip-flop phenomenon occurred) than that of MRTt (calculated using data from zero time through the last sampling time). However, the power of MRTt was shown to be comparable to or higher than that of either AUCt or Cmax (the peak drug concentration) from simulated data. These results were also confirmed experimentally using previously obtained data. The effect of variances of plasma concentrations on the power of these parameters was also studied using a simulation technique. Even large variances near the last sampling time did not substantially affect the power of MRTt. Thus MRTt can be used as a parameter for estimating the rate of bioavailability from dosage forms in place of tmax in bioequivalence tests.

Biological Availability↗
PubMed1988

Gastric emptying rates of drug preparations. I. Effects of size of dosage forms, food and species on gastric emptying rates.

The gastric emptying rates of oral dosage forms of different sizes were studied in humans and beagle dogs measuring of marker drugs such as acetaminophen, aspirin and pyridoxal phosphate in plasma or urine. The marker drugs, except acetaminophen, were contained in enteric-coated granules or tablets which did not dissolve in the stomach but dissolved rapidly in the upper intestine. The gastric emptying rate of a dosage form of smaller size was faster than that of a larger size. The gastric emptying rates of dosage forms with different sizes did not correlate with each other inter-individually. The gastric emptying rates of dosage forms of any size were delayed when drugs were administered after taking a meal. The gastric emptying rates of dosage forms were extremely prolonged in beagle dogs after drug administration postprandially, and this restricted the use of beagle dogs as an animal model in bioavailability tests.

Acetaminophen↗
PubMed1988

Gastric emptying rates of drug preparations. II. Effects of size and density of enteric-coated drug preparations and food on gastric emptying rates in humans.

Enteric-coated granules with different densities and tablets of different sizes were prepared in order to study the effect of these physical properties of dosage forms on the gastric emptying rates in humans. The effect of food on the gastric emptying rate was also studied. Aspirin contained in an enteric-coated product as a marker drug was used to determine the gastric emptying rate by measuring salicylates excreted into the urine. The larger the size of the dosage form, the larger were the values of parameters for estimating the gastric emptying rate such as tlag, tmax and the mean absorption time. There was a significant correlation between the gastric emptying rates and sizes of dosage forms. On the other hand, no effects of density of enteric-coated granules on the gastric emptying rate were observed. The gastric emptying of dosage forms of various sizes or densities tested were prolonged by food. However, the gastric emptying rate of granules was less affected by food than that of tablets.

Aspirin↗
PubMed1986

Effect of food on bioavailability of metronidazole from sugar-coated tablets having different dissolution rates in subjects with low gastric acidity.

The effect of food on the bioavailability of metronidazole from three commercial sugar-coated tablets varying markedly in drug dissolution behavior relative to pH was determined after oral administration in healthy male subjects with low gastric acidity. Four subjects, whose gastric acidities were evaluated as low (hypo- or anacidity) by using a non-intubation method (Gastrotest tablets administration method), received, in a cross-over fashion, a single 250 mg dose in sugar-coated tablet during periods of fasting and non-fasting. The tablet having the fastest and most pH-independent dissolution rate gave significantly higher Cmax and AUC0-32 than the other tablets having extremely slow dissolution at pH 5 or 7.2, when the drug was administered in the fasting state. However, there were no statistically significant differences in the above parameters among the tablets tested when they were administered postprandially. The improvement of the bioavailability of the tablets exhibiting poorer dissolution in the pH range of 5 to 7.2 is ascribed to suggestible vigorous agitation in the digestive tract stimulated by food intake.

Adult↗