Role of intestinal excretion in the effect of subcutaneously administered sedecamycin on cecal infection caused by Treponema hyodysenteriae in mice.
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.
Hayashi
T
T
Animal Health Research Laboratory, Takeda Chemical Industries, Ltd., Osaka, Japan.
Okada
J
J
Kondo
S
S
Yamazaki
T
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D001652:Bile Ducts / Q000502:physiology; D002429:Cecal Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D002432:Cecum / Q000378:metabolism; D005260:Female; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000378:metabolism*; D008026:Ligation; D018942:Macrolides; D051379:Mice; D014211:Treponemal Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology
D000900:Anti-Bacterial Agents; D018942:Macrolides; C054134:sedecamycin