直腸薬物送達を指向した新規潰よう性大腸炎治療薬ＯＮＯ‐４０５７の生体粘膜付着性Ｅｕｄｉｓｐｅｒｔゲル製剤

Abstract

Eudispert hv hydrogel and xerogel preparations containing ONO-4057(5-[2-carboxyethyl)3-{6-(4-methoxyphenyl)-5E-hexenyl}oxyphenoxy]valeric acid), a new leukotriene B4 antagonist, were prepared, and evaluated in rats following rectal administration of these preparations. For rectal administration of gel preparations, the absolute bioavailability of ONO-4057 was almost the same (approximately 30%) as that for oral administration (31%) and also quite low compared with those of Witepsol H-15 or PEG 2000 suppositories (37% and 56%). The residual amounts in the intestine and rectum tubes and the accumulative amounts in the intestine and rectum tissues of ONO-4057 following oral and rectal administrations of various preparations were measured. The results indicate that the residual and accumulative amounts of ONO-4057 for eudispert hv gel preparations increased 2∼5 folds compared with administration of oral and two conventional suppositories. Accordingly, it is assumed that eudispert hv hydrogel and xerogel preparations have excellent staying properties in the lower part of rectum and can directly act to focus parts of ulcerative colitis by raising ONO-4057 concentrations in rectum and its tissue.