Kumakura S, Mishima M, Kobayashi S, Shirota H, Abe S, Yamada K, Tsurufuji S
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Agents Actions. 1990 Mar;29(3-4):286-91. doi: 10.1007/BF01966459.
Antiinflammatory effects of indomethacin farnesil (IMF), a novel prodrug of indomethacin, was examined after both oral and local administration. In the air pouch carrageenin-induced inflammation, an oral dose of IMF exerted dose dependent inhibitory effects on the accumulation of inflammatory exudate fluid and the migration of leukocytes into the exudate. Both the increased vascular permeability and the prostaglandin E2 levels in the exudate fluid were reduced by IMF. Significant levels of free indomethacin were detected in the pouch fluid. In spite of the inability of IMF to inhibit prostaglandin synthesis in a cell free cyclooxygenase system, IMF injected locally inhibited carrageenin paw edema, and the inhibitory effect was comparable to that of indomethacin itself. When injected locally into the paw together with carrageenin, 14C-IMF was effectively converted to its active metabolite, indomethacin. The indomethacin concentration in the paw tissue was comparable to that of indomethacin injected paws with the same molar dose of free indomethacin.
对新型吲哚美辛前药法尼醇吲哚美辛（IMF）在口服和局部给药后的抗炎作用进行了研究。在气囊角叉菜胶诱导的炎症中，口服剂量的IMF对炎性渗出液的积聚以及白细胞向渗出液中的迁移具有剂量依赖性抑制作用。IMF降低了渗出液中增加的血管通透性和前列腺素E2水平。在囊液中检测到显著水平的游离吲哚美辛。尽管IMF在无细胞环氧化酶系统中无法抑制前列腺素合成，但局部注射IMF可抑制角叉菜胶诱导的爪肿胀，其抑制作用与吲哚美辛本身相当。当与角叉菜胶一起局部注射到爪中时，14C-IMF可有效转化为其活性代谢产物吲哚美辛。爪组织中的吲哚美辛浓度与以相同摩尔剂量的游离吲哚美辛注射到爪中的浓度相当。
