title: Use of tissue-fluid correlations to estimate gentamicin residues in kidney tissue of Holstein steers.
abstract: Gentamicin continues to be one of the most effective antibiotics for the treatment of gram-negative infections. Greater than 90% of the drug is rapidly eliminated from the body in <2 days, however, a small residue remains bound to the kidney cortex tissue for many months. In beef steers, the gentamicin residue is unacceptable and its presence is monitored by the FAST (Fast Antimicrobial Screen Test) applied to the kidney at the time of slaughter. The sensitivity of the FAST to gentamicin in the kidney cortex is reported to be 100 ng/g, therefore, this level of gentamicin defines the acceptable limit of gentamicin drug residue in the bovine kidney. In the present study, three doses of 4 mg/kg gentamicin was administered intramuscularly to eight steers. Gentamicin was allowed to deplete from the kidneys for a range of times from 7 to 10 months. At slaughter the level of gentamicin in the kidney cortex varied from 91 to 193 ng/g, but a total of 160 FAST tests performed on the kidneys were negative. Blood and urine samples were collected at varying times following the last dose of gentamicin. Kidney tissue samples were collected by laparoscopic surgery in the live steers as well as the final sample obtained at slaughter. Plasma levels of gentamicin declined rapidly to nondetectable within 3 days, while measurable urine persisted for 75 days before the concentration of gentamicin declined to levels too low to quantitate by the available liquid chromatography tandem mass spectrometry (LC/MS/MS) technique. An estimated correlation between an extrapolation of urine gentamicin concentration to the corresponding kidney tissue sample suggests a urine to kidney tissue relationship of 1:100. A test system sufficiently sensitive to a urine gentamicin concentration of 1 ng/mL will correlate with the estimated 100 ng/g gentamicin limit of the FAST applied to the fresh kidney of the recently slaughtered bovine.
authors.affiliation: Division of Residue Chemistry, Center for Veterinary Medicine, Office of Research, Food and Drug Administration, Laurel, MD 20708, USA. ochiesa@cvm.fda.gov
authors.forename: O A
authors.initials: OA
authors.lastname: Chiesa
authors.forename: J
authors.initials: J
authors.lastname: von Bredow
authors.forename: D
authors.initials: D
authors.lastname: Heller
authors.forename: C
authors.initials: C
authors.lastname: Nochetto
authors.forename: M
authors.initials: M
authors.lastname: Smith
authors.forename: K
authors.initials: K
authors.lastname: Moulton
authors.forename: M
authors.initials: M
authors.lastname: Thomas
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000032:analysis* / Q000097:blood / Q000652:urine; D002417:Cattle; D004350:Drug Residues / Q000378:metabolism*; D005839:Gentamicins / Q000032:analysis* / Q000097:blood / Q000652:urine; D007668:Kidney / Q000737:chemistry*; D008297:Male; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins