Human Food Safety Implications of Variation in Food Animal Drug Metabolism.
Violative drug residues in animal-derived foods are a global food safety concern. The use of a fixed main metabolite to parent drug (M/D) ratio determined in healthy animals to establish drug tolerances and withdrawal times in diseased animals results in frequent residue violations in food-producing animals. We created a general physiologically based pharmacokinetic model for representative drugs (ceftiofur, enrofloxacin, flunixin, and sulfamethazine) in cattle and swine based on extensive published literature. Simulation results showed that the M/D ratio was not a fixed value, but a time-dependent range. Disease changed M/D ratios substantially and extended withdrawal times; these effects exhibited drug- and species-specificity. These results challenge the interpretation of violative residues based on the use of the M/D ratio to establish tolerances for metabolized drugs.
Institute of Computational Comparative Medicine (ICCM), Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
Zhoumeng
Z
Lin
Department of Statistics, College of Arts and Sciences, Kansas State University, Manhattan, KS 66506, USA.
Christopher I
CI
Vahl
Institute of Computational Comparative Medicine (ICCM), Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
Jim E
JE
Riviere
D000818:Animals; D002138:Calibration; D002417:Cattle; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics; D003002:Clonixin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004350:Drug Residues / Q000032:analysis / Q000493:pharmacokinetics; D000077422:Enrofloxacin; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics; D005506:Food Contamination; D059022:Food Safety; D006801:Humans; D008962:Models, Theoretical; D013045:Species Specificity; D013418:Sulfamethazine / Q000008:administration & dosage / Q000493:pharmacokinetics; D013552:Swine; D019155:Veterinary Drugs / Q000008:administration & dosage / Q000493:pharmacokinetics*
D002511:Cephalosporins; D024841:Fluoroquinolones; D019155:Veterinary Drugs; C014557:flunixin; D000077422:Enrofloxacin; D013418:Sulfamethazine; C053503:ceftiofur; D003002:Clonixin