Hayashi T, Okada J, Kondo S, Yamazaki T
Animal Health Research Laboratory, Takeda Chemical Industries, Ltd., Osaka, Japan.
Antimicrob Agents Chemother. 1991 Aug;35(8):1601-4. doi: 10.1128/AAC.35.8.1601.
The therapeutic effects of subcutaneously administered sedecamycin on experimental Treponema hyodysenteriae infection in mice were evaluated. Sedecamycin was more active than tiamulin and lincomycin. The efficacy of sedecamycin upon subcutaneous administration was similar to that upon oral administration. Sedecamycin given subcutaneously provided similar degrees of protection in bile duct-ligated and intact mice. Pharmacokinetic studies utilizing a liquid chromatographic technique were carried out to determine the concentration of sedecamycin in the cecum, the site of T. hyodysenteriae infection in mice. Little sedecamycin was found; however, lankacidinol, a major metabolite of sedecamycin, was found in the cecal contents of intact mice after subcutaneous or oral administration of sedecamycin. Lankacidinol was also found in the cecal contents of bile duct-ligated mice, although the concentration found after subcutaneous administration of sedecamycin was much lower than that found after subcutaneous or oral administration to intact mice. These results indicate that sedecamycin is excreted directly into the intestinal tract as an active metabolite by a route other than the bile duct. It is suggested that this intestinal excretion plays an important role in the efficacy of subcutaneously administered sedecamycin against cecal infection of mice by T. hyodysenteriae.
评估了皮下注射塞地卡霉素对小鼠实验性猪痢疾密螺旋体感染的治疗效果。塞地卡霉素比泰妙菌素和林可霉素更具活性。皮下给药时塞地卡霉素的疗效与口服给药相似。皮下注射塞地卡霉素在胆管结扎小鼠和未结扎小鼠中提供了相似程度的保护。利用液相色谱技术进行了药代动力学研究,以测定塞地卡霉素在小鼠盲肠(猪痢疾密螺旋体感染部位)中的浓度。未发现多少塞地卡霉素;然而,在皮下或口服塞地卡霉素后,在未结扎小鼠的盲肠内容物中发现了塞地卡霉素的主要代谢产物兰卡地醇。在胆管结扎小鼠的盲肠内容物中也发现了兰卡地醇,尽管皮下注射塞地卡霉素后发现的浓度远低于对未结扎小鼠皮下或口服给药后发现的浓度。这些结果表明,塞地卡霉素以活性代谢产物的形式通过胆管以外的途径直接排泄到肠道中。有人认为,这种肠道排泄在皮下注射塞地卡霉素对小鼠盲肠猪痢疾密螺旋体感染的疗效中起重要作用。