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Biomedical subjects

A Ejima

Publications and source records attributed to A Ejima.

At least 19 recordsLinked to original sources
PubMed1992

[Cerebellar atrophy and persistent cerebellar ataxia after acute intoxication of phenytoin].

Chronic intoxication of phenytoin (PHT) is a well known cause of cerebellar atrophy or irreversible cerebellar ataxia. Little attention, on the other hand, is paid for acute PHT intoxication because its clinical signs are believed to be reversible. We here report a patient with acute PHT intoxication, which resulted in irreversible cerebellar ataxia with radiologically definite cerebellar atrophy. A 39-year-old man admitted to our hospital because of cerebellar ataxia and confusional state. He had been treated with PHT for convulsive seizures after receiving craniotomy for left parietal brain abscess 9 years before. The concentration of his serum PHT had been 4 to 7 micrograms/ml because he had frequently omitted taking drug, and the dose of PHT had been increased to 600 mg/day one year before. He had admitted to another hospital 2 months before for left Bell's palsy and had been obliged to take drug regularly. Cerebellar signs and confusion had gradually developed for 7 weeks. On admission to our hospital, he was awake but in severe confusional state with slurred speech and nystagmus. His serum PHT was 86 micrograms/ml, which returned to therapeutic range 2 weeks after the discontinuation of PHT. His consciousness normalized and nystagmus disappeared. However, slurred speech continued and neurological examination revealed postural tremor and severe limb ataxia. During the subsequent 10 months, his cerebellar signs showed minimal improvement. Computed tomographies of his brain on 3rd and 5th month after the onset of his cerebellar dysfunction showed the definite cerebellar atrophy which had not been noted on the CTs 7 months before and 7 weeks after the onset.(ABSTRACT TRUNCATED AT 250 WORDS)

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↗
PubMed1989

Synthesis and antileukemic activity of (+-)-20-deoxyaminocamptothecin analogues.

The camptothecin analogues (+-)-7-ethyl-10-methoxy-20-deoxyaminocamptothecin (2) and (+-)-7-ethyl-10-hydroxy-20-deoxyaminocamptothecin.HCl (3) were synthesized from indolizine compound 4 via Friedländer condensation to construct a pentacyclic ring system, and were tested in a P388 mouse antileukemia assay. Compounds 2 and 3 were more active and less toxic than (+)-camptothecin (1), and therefore had higher therapeutic ratios.

Animals↗
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↗
PubMed1987

Synthesis and antimicrobial activity of cephalosporins with a 1-pyridinium substituent carrying a 5-membered heterocycle at the C-3 position.

A series of potent antimicrobial agents have been prepared. These derivatives are cephalosporins carrying a pyridine ring substituted with a heterocycle in the C-3 position. Some of them showed excellent activity not only against Gram-negative organisms including Pseudomonas aeruginosa but also against Gram-positive ones. In view of their biological and physico-chemical properties, 7 beta-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[4-(2 or 5-oxazolyl)-1-pyridinium]methyl-3-cephem-4-carboxylate 8f (DQ-2522) and 8g (DQ-2556) were chosen as candidates for further evaluation.

Cephalosporins↗
PubMed1986

Semisynthetic beta-lactam antibiotics. I. Synthesis and antibacterial activity of 7 beta-[2-aryl-2-(aminoacetamido)acetamido]-cephalosporins.

The synthesis and in vitro structure-activity relationships of cephalosporins having dipeptides substituted with various aryl groups as the side chain at the C-7 position have been outlined. Of these compounds, 2-aminothiazol derivatives showed a broad spectrum of enhanced antibacterial activity, and 7 beta-[DL-2-(D-aminopropionamido)-2-(2-aminothiazol-4-yl)acet amido]-3- [(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxyli c acid was the most balanced of these active derivatives with respect to both Gram-positive and Gram-negative strains.

Bacteria↗
PubMed1986

Semisynthetic beta-lactam antibiotics. II. Synthesis and antibacterial activity of 7beta-[2-(acylamino)-2- (2-aminothiazol-4-yl)acetamido]cephalosporins.

Cephalosporin derivatives (I) substituted with a neutral, acidic or basic amino acid group as the terminal group attached to the 2-amino-2-(2-aminothiazol-4-yl)acetamido side chain at the C-7 position were synthesized, and the effect of each group on antibacterial activity was examined. The derivatives bearing an amidino or guanidino group showed broad spectra of antibacterial activity similar to those of cefotaxime, but they were relatively sensitive to beta-lactamases.

Bacteria↗
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↗
PubMed1985

Bioavailability of indomethacin capsules in humans. (I): Bioavailability and effects of gastric acidity.

The bioavailabilities of five indomethacin capsules, two commercial and three experimental products, were studied in ten human subjects. The bioavailabilities of the products increased in proportion to their in vitro dissolution rates, although one of the commercial products provided a relatively lower bioavailability than was expected. Comparison of the bioavailabilities between high and low gastric acidity humans revealed that the serum levels of the drug during the absorption phase following oral administration of all the indomethacin products, except for one commercial product, were higher in the low acidity subjects than in the high acidity subjects. Also, the mean peak serum level of the most rapidly dissolving product was 1.6 times higher in the low acidity subjects than in the high acidity ones. These gastric acidity effects indicated enhanced dissolution of indomethacin from the capsules in the stomach of low acidity humans.

Adult↗