Search PubMed⌕ Search

Biomedical subjects

F Hirayama

Publications and source records attributed to F Hirayama.

143 records · Page 8Linked to original sources

[Phase II study of mitoxantrone for acute leukemia].

A total of seventeen patients with acute leukemia were treated with mitoxantrone for induction therapy. Nine out of 17 patients were previously untreated, while the other eight patients were previously treated. All of the previously treated cases had received chemotherapy including anthracycline derivatives. Bolus infusion of Mitoxantrone for three to ten days was employed. The daily and total doses of mitoxantrone ranged from 1.8 mg/m2 to 4.3 mg/m2 and from 7.5 mg/m2 to 40 mg/m2, respectively. CR was achieved in three (33%) previously untreated and two (25%) in previously treated cases. PR occurred in five previously untreated and in two previously treated patients. The other five failed to respond the agent. The most serious adverse effect of the drug was myelosuppression, but it was reversible in all cases. In one patient irreversible EKG change was observed. All other adverse effects such as nausea and vomiting, anorexia and diarrhea, were not serious and reversible. In conclusion, Mitoxantrone is effective in some cases with acute leukemia.

Acute Disease↗

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↗

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↗

Improvements of dissolution characteristics and chemical stability of 16,16-dimethyl-trans-delta 2-prostaglandin E1 methyl ester by cyclodextrin complexation.

Inclusion complexation of 16,16-dimethyl-trans-delta 2-prostaglandin E1 methyl ester (I), which is effective in early pregnancy termination, with cyclodextrins in water was ascertained by a solubility study. A solid complex of I-beta-cyclodextrin in a 1:2 molar ratio was obtained, and its dissolution behavior and chemical stability were examined. The results indicated that the complex may have great utility as a rapidly dissolving form of I with prolonged storage time.

Biopharmaceutics↗

Utilization of cyclodextrin complexation for separation of E, A, and B prostaglandins by ion-exchange liquid chromatography.

Application of cyclodextrin complexation to the separation of E-, A-, and B-type prostaglandins by ion-exchange liquid chromatography is demonstrated. The addition of alpha-or beta-cyclodextrin into the mobile phase on an anion-exchange support decreased the retention times of the prostaglandins significantly because of soluble complex formation. Chromatographic separation behavior is discussed on the basis of the stability of the inclusion complex. A rapid and sensitive method for the separation and quantification of the prostaglandins, using beta-cyclodextrin in the mobile phase, is described.

Chemical Phenomena↗

Enhancement of gene expression by polyamidoamine dendrimer conjugates with alpha-, beta-, and gamma-cyclodextrins.

To improve the transfection efficiency of nonviral vector, we synthesized the starburst polyamidoamine dendrimer conjugates with alpha-, beta-, and gamma-cyclodextrins (CDE conjugates), expecting the synergistic effect of dendrimer and cyclodextrins (CyDs). The (1)H NMR spectroscopic data indicated that alpha-, beta-, and gamma-CyDs are covalently bound to dendrimer in a molar ratio of 1:1. The agarose gel electrophoretic studies revealed that CDE conjugates formed the complexes with plasmid DNA (pDNA) and protected the degradation of pDNA by DNase I in the same manner as dendrimer. CDE conjugates showed a potent luciferase gene expression, especially in the dendrimer conjugate with alpha-CyD (alpha-CDE conjugate) which provided the greatest transfection activity (approximately 100 times higher than those of dendrimer alone and of the physical mixture of dendrimer and alpha-CyD) in NIH3T3 and RAW264.7 cells. In addition, the gene transfer activity of alpha-CDE conjugate was superior to that of Lipofectin. The enhancing gene transfer effect of alpha-CDE conjugate may be attributable to not only increasing the cellular association, but also changing the intracellular trafficking of pDNA. These findings suggest that alpha-CDE conjugate could be a new preferable nonviral vector of pDNA.

3T3 Cells↗