ANALYSIS OF TISSUE RESIDUES AND COMPARATIVE METABOLISM OF ARDACIN IN CATTLE, BROILERS, AND RATS

摘要

Following continuous administration, ardacin residues equilibrated in tissues of cattle and broilers after 13 and 22 days, respectively, with average total residues of <111 ppb in all tissues. Kidney contained the highest residues in cattle, while liver was higher in broilers. Milk residues from treated dairy cows averaged only 2.1 ppb. Extraction of liver and kidney using 50% KOH/ACN removed 23-68% of the total radioactive residues. Balance-excretion studies demonstrated that greater than or equal to 98% of the administered radioactivity was eliminated in the feces of all species studied. Comparative metabolism studies demonstrated that ardacin was not significantly biotransformed as the parent compound was detected in excreta and tissues from cattle, broilers, and rats. Microbiological assays of tissue and fecal extracts confirmed the presence of ardacin as antimicrobial potency results paralleled those obtained by HPLC. The low tissue residues and favorable safety profile has qualified ardacin for 0-day withdrawal in both cattle and broilers.