DISTRIBUTION AND ANTITUMOR ACTIVITY OF DEPOT BLEOMYCIN:With Special Reference to the Treatment of Experimental Brain Tumor
スポンサーリンク
概要
- 論文の詳細を見る
The uptake and distribution of bleomycin, a kind of watersoluble antibiotic, were previously studied in mice with methylcholanthrene induced glioma by means of biological and radioactive assaywith <SUP>14</SUP>C-bleomycin A<SUB>2</SUB>. The result obtained showed that a relative large amount of bleomycin may be taken up selectively in glioma after intravenous administration, and about two-thirds of bleomycin distributed in glioma may remain in active form with antimicrobial activity. Furthermore, a tendency was clinically noted that the more malignant was the tumor, the higher was the uptake of bleomycin.<BR>In has been thought that administration of drug in depot preparation, permitting slow release of the drug contained from an administration site, may change the distribution and uptake of drug in tumortissue and may change its effectiveness. The present study was designed to study the influence of the vehicles of bleomycin for depot preparations with special reference to the chemotherapy of brain tumor.<BR>As the first step of the experiments, the binding affinity of the drug to serum protein, which is said to be closely related to the distribution and antitumor activity of the drug, was investigated byequilibrium dialysis. Evidence obtained indicated that bleomycin A<SUB>2</SUB>, main component of commercial bleomycin, has low affinity of binding to horse serum proteins and bleomycin A<SUB>5</SUB> has moderate, though mitomycin C, another kind of antitumor antibiotic, has high affinity.<BR>As the next step, the following three kinds of preparations containing bleomycin (supplied by Nippon Kayaku Co., Ltd.) were employed for depot administration ; so called oil bleomycin (suspending vehicle : sesame oil : 99%, aluminum monostearate : 1%), solid bleomycin (sesame oil : 17. 8%, Witepsol E 85 : 80. 8%, Tween 80 : 2. 2%), and paste bleomycin (sesame oil : 54%, bleached beeswax : 24%, polyvinyl pyrrolidone : 22%).<BR>The dissolution curves of active bleomycin from three depot types of vehicles to saline were studied <I>in vitro</I>. Fifty per cent of bleomycin contained was dissolved from depot preparations to placed salinewithin 24 to 96 hours. Then, the distribution and uptake of active bleomycin in the organs and tumor investigated in mice with subcutaneously transplanted glioma. As a result, it was clear that a few hours after administration, the distribution and uptake of active bleomycin in the organs and tumor tissue after oil bleomycin administration usually exceeded those after saline bleomycin administration and maintained considerably high level for longer time.<BR>As the final step, the effects of depot bleomycin on the tumor growth and body weight change were studied in above mentioned experimental animals. Evidence indicated that intramuscular administration of oil bleomycin (15 mg/kg x 5) apparently supressed the transplanted glioma growth, but no significant difference between the effect of oil bleomycin and saline bleomycin on the tumor growth was observed in this trial. Based on these results, it may be concluded that the application of depot preparations for administration of bleomycin changes the distribution and uptake of the drug in the organs and tumor tissue and possibly results in increase of the effectiveness of the drug against tumor and reduction of the systemic toxicity, if the compositions of depot preparations would be improved.
- 公益社団法人 日本化学療法学会の論文
公益社団法人 日本化学療法学会 | 論文
- DISPOSITION OF 7432-8 IN RATS (I)
- CLINICAL STUDIES ON T-1220 IN SURGICAL CASES
- CLINICAL STUDIES OF PIVALOYLOXYMETHYL D-α-AMINOBENZYL-PENICILLINATE HYDROCHLORIDE IN SURGICAL INFECTIONS
- STUDIES ON AC-1370
- Primary treatment with a combination of cyclophosphamide, vincristine, and dacarbazine for recurrent malignant pheochromocytoma: A case report.