Pirlimycin residue in bovine liver--a case of reverse metabolism

Samples of liver obtained from twenty dairy cows treated with pirlimycin hydrochloride (Pirsue) by the intramammary route and slaughtered at five different time intervals out to 28 days were incubated at room temperature and at 37 degrees C and analyzed by two HPLC-MS methods to examine the metabolite profile of the residue and to establish the quantitative relationship of the residue components. The evidence from these experiments suggests that the metabolism of pirlimycin in postmortem bovine liver is somewhat reversible, where the concentration of parent pirlimycin increases in the incubated liver with a concomitant reduction in the concentration of the pirlimycin sulfoxide metabolite. This increased parent-drug residue phenomenon is limited to liver and was not observed in kidney or muscle. The highest relative change in concentration was observed for low level biologically incurred samples and appeared to be a saturable process following Michaelis-Menten kinetics. All of the evidence collected appears to indicate that the phenomenon is the result of residual enzyme activity present in the postmortem liver samples and likely involves some type of reductase enzyme capable of reducing sulfur-oxidized substrates to the sulfide state. No attempts were made to identify specific enzymes responsible for this phenomenon.