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Biomedical subjects

K Uekama

Publications and source records attributed to K Uekama.

At least 127 records · Page 7Linked to original sources
PubMed1983

Improvement of the oral bioavailability of digitalis glycosides by cyclodextrin complexation.

Inclusion complexes of the digitalis glycosides digitoxin, digoxin, and methyl digoxin with three cyclodextrins (alpha-, beta-, gamma-homologues) in water and in the solid state were studied by a solubility method, IR and 1H-NMR spectroscopy, and X-ray diffractometry. Solid complexes (in a molar ratio of 1:4) of the digitalis glycosides with gamma-cyclodextrin were prepared and their in vivo absorption examined. The rapidly dissolving form of the gamma-cyclodextrin complex significantly increased plasma levels of digoxin (approximately 5.4-fold) after oral administration to dogs.

Animals↗
PubMed1983

Improvement of oral bioavailability of prednisolone by beta-cyclodextrin complexation in humans.

Inclusion complex of prednisolone with beta-cyclodextrin (beta-CyD) in 1:2 molar ratio was prepared and its dissolution, membrane permeation and oral absorption behaviors were examined. The rates of dissolution and permeation through a cellophane membrane in water were significantly increased by beta-CyD complexation. A crossover bioavailability study was performed using human subjects with lower doses of prednisolone tablets, where the plasma levels of the drug were determined by radioimmunoassay. The enhanced bioavailability of prednisolone by beta-CyD complexation suggested the possibility of smaller doses and fewer side effects in prednisolone therapy.

Adult↗
PubMed1983

Protective mechanism of beta-cyclodextrin for the hemolysis induced with phenothiazine neuroleptics in vitro.

beta-Cyclodextrin (beta-CyD) was found to protect the human erythrocytes from the hemolysis induced with ten phenothiazine neuroleptics in isotonic solution. The hemolytic activities of the phenothiazine-beta-CyD systems appeared to depend upon the free phenothiazine concentration, suggesting that the complexed form of phenothiazines is essentially inactive to cause hemolysis. The binding abilities and surface activities of the complexed form of phenothiazines were much smaller than those of free phenothiazines. These results indicate that the protective effect of beta-CyD may be due to the decrease in the effective hemolytic concentration of phenothiazines by inclusion complexation rather than the stabilizing effect of beta-CyD on the erythrocyte membrane.

Antipsychotic Agents↗
PubMed1983

Reduction in the local tissue toxicity of chlorpromazine by beta-cyclodextrin complexation.

Effect of beta-cyclodextrin (beta-CyD) on the local tissue toxicity of chlorpromazine (CPZ) was investigated following the intramuscular injection to rabbits. From the gross and histological examinations, beta-CyD was found to alleviate the muscular tissue damage produced by CPZ on M. vastus lateralis in rabbits. The protective effect of beta-CyD may be ascribed to the decrease in affinity of CPZ to the tissue membrane through inclusion complexation. The present data suggest that beta-CyD complexation is particularly useful to reduce the local toxicity of phenothiazine neuroleptics without altering the pharmacological efficacy.

Animals↗
PubMed1982

Effect of cyclodextrins on the acid hydrolysis of digoxin.

The effects of three cyclodextrins (alpha-, beta-, gamma-CyD) on the acid hydrolysis of digoxin were examined. From the high performance liquid chromatographic tracing of each of the four components (digoxin, bisdigitoxoside, monodigitoxoside, digoxigenin) in reaction mixtures, the individual rate constants (K1-K6) were determined by analogue computer simulation. The hydrolysis was suppressed by CyDs in the order of beta-great than gamma-greater than alpha-greater than-CyD, where beta-CyD inhibited the appearance rates of digoxigenin (k3, K5, and K6) significantly. In the dissolution study of digoxin tablets, the increase in dissolution rate and decrease in acid hydrolysis were attained by inclusion complexation. The data are presented suggesting that CyDs are useful for improving the oral bioavailability of digoxin.

Chromatography, High Pressure Liquid↗
PubMed1982

Enhanced oral bioavailability of antiinflammatory drug flurbiprofen in rabbits by tri-O-methyl-beta-cyclodextrin complexation.

Inclusion complex of antiinflammatory drug flurbiprofen with tri-O-methyl-beta-cyclodextrin in 1:1 molar ratio was prepared, and its dissolution and absorption characteristics were compared with those of flurbiprofen. The apparent dissolution rate of flurbiprofen in water was significantly increased by the inclusion complexation. The serum level of flurbiprofen following the oral administration of the complex to rabbits was higher than that of the drug alone. The enhanced bioavailability of flurbiprofen suggests the possible utility of tri-O-methyl-beta-cyclodextrin in pharmaceutical formulation.

Administration, Oral↗