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标题：Preparation and Evaluation of Suppositories for RK-28 (a New Radiosensitizer) Using Rabbits
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作者：NakSeo KIM ; Hiroyuki UMEJIMA ; Kaori MIYATA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1994
卷号：17
期号：5
页码：672-675
DOI：10.1248/bpb.17.672
出版社：The Pharmaceutical Society of Japan
摘要：The pharmacokinetics of RK-28 [1-(4-hydroxy-2-butenoxy) methyl-2-nitroimidazole], a new hypoxic cell radiosensitizer, was studied following intravenous, oral, and rectal administration to rabbits. After an oral administration of RK-28 solution, the plasma concentration of RK-28 was considerably lower than that after intravenous administration through all time periods, and the absolute bioavailability was a mere 4.2%. It was presumed that a specific acid-catalized decomposition of RK-28 progressed in the stomach, and also, the absorbed RK-28 suffered first-pass effects in the liver. In contrast, the absolute bioavailability following the rectal administration of a solidified RK-28 suppository preparation was significantly increased in comparison with that obtained by other administration routes. Also, RK-28 emulsion suppositories were prepared by emulsifying various amounts of the drug with 1-hexadecanol and hydrogenated castor oil (HCO 60) at 80°C, and these were administered into the rabbit rectum. The resulting absolute bioavailability was 91% for the RK-28 emulsion suppository and 86.9% for an RK-28 emulsion suppository containing small amounts of Eudispert hv. These values were better than those in rats. The rectal administration of the RK-28 emulsion suppository containing small amounts of Eudispert hv showed a preferable plasma concentration-time pattern that reflects on radiation therapy.
关键词：RK-28 emulsion suppository;1-hexadecanol;Eudispert hv;hydrogenated castor oil (HCO 60);absolute bioavailability;radiosensitizer