Virginiamycin metabolism in cattle rumen fluid.
The antibiotic virginiamycin (VM) was extensively metabolized in cattle rumen fluid in vitro. The antimicrobial activity of VM decreased rapidly with an initial half-life of approximately 8 hr. In contrast, in buffer at near neutral pH, VM maintained its full activity for at least 24 hr. Four metabolites were isolated and identified using a combination of spectral techniques including FAB MS-MS, LC-MS, and 500 MHz NMR. The metabolites were all derived from reduction of the major component of virginiamycin, factor M. The minor component, factor S, was not metabolized in cattle rumen fluid. The metabolic pathways involved included C = C and C = O reduction as well as dehydroxylation. All metabolites were found to have less antimicrobial activity than the parent factor M. In addition to the metabolites, two factor M decomposition products were isolated after incubation of VM in buffer alone. These two products resulted from the dehydration of factor M and were shown to interconvert at room temperature.
Gottschall
D W
DW
Department of Drug Metabolism and Bioanalytical Services, SmithKline Beckman Animal Health Products, West Chester, PA 19380.
Wang
R
R
Kingston
D G
DG
D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005285:Fermentation; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D012417:Rumen / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D014769:Virginiamycin / Q000378:metabolism*
D014769:Virginiamycin