title: Depletion of gentamicin in the milk of Holstein cows after single and repeated intramammary and parenteral treatments.
abstract: Twenty-four healthy Holstein cows, 2.72 +/- 0.64 (mean +/- SD) years old, weighing 603.96 +/- 73.22 kg (mean +/- SD), and representing various levels of milk production, were used to determine the depletion of gentamicin (GT) in milk. The cows had not received antibiotics or other drugs that could interfere with study for at least 60 days before the beginning of the investigation. The cows were divided into six groups (n = 4) and treated with single (treatments A, B and C) or repeated (treatments D, E and F) doses of GT. Cows were acclimated for 7 days before administration of GT and milked twice a day at 12-h intervals (06.00 hours, 18.00 hours) throughout the duration of the study. Control milk samples were obtained after the arrival of the cows and assayed to establish their GT free status. On day 1 of each treatment, a baseline milk sample was collected from the milk produced (06.00 hours) by each cow. A single dose of GT was administered intramammarily (A, i.m.m. left front quarter, 500 mg), intravenously (B, i.v., 5 mg/kg body weight) or intramuscularly (C, i.m., 5 mg/kg body weight). Cows in treatments D (i.m.m., 500 mg), E (i.v., 5 mg/kg body weight) and F (simultaneous i.m.m. 500 mg plus i.v. 5 mg/kg body weight) were treated twice a day for 5 consecutive days just after the morning and evening milkings. Milk samples from individual cows were collected every day after each milking during and after dosing until GT concentration in the milk was below the safe level of < or = 30 ng/mL. The concentration of GT in milk was determined by a high-performance liquid chromatographic procedure. Depletion of GT to a concentration < or = 30 ng/mL occurred at the seventh (84 h), third (36 h), third (36 h), eleventh (132 h) third (36 h) and nineteenth (228 h) post-dosing milking, for cows in treatments A, B, C, D, E and F respectively. The highest mean +/- SEM) concentrations of GT were 14 710 +/- 1213.89, 167.87 +/- 46.94 and 91.62 +/- 14.55 ng/mL measured in the first milking post dosing (12 h) for cows in treatment A, B and C respectively; for cows in treatments D, E and F, during the dosing period, they were 14067.50 +/- 2989.09, 446.07 +/- 100.92, and 22900 +/- 2843.66 ng/mL and occurred at the seventh, third and eighth milking respectively. Because GT is not approved for use in dairy cattle and because of the long depletion time associated with some possible treatments, illegal and extra-label use is likely to cause residues in milk.
authors.affiliation: Division of Animal Research, FDA-CVM, Beltsville, Maryland 20705, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Pedersoli
authors.forename: J
authors.initials: J
authors.lastname: Jackson
authors.forename: R A
authors.initials: RA
authors.lastname: Frobish
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D002417:Cattle / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004305:Dose-Response Relationship, Drug; D004350:Drug Residues / Q000032:analysis / Q000493:pharmacokinetics*; D005260:Female; D005506:Food Contamination; D005839:Gentamicins / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D008321:Mammary Glands, Animal / Q000378:metabolism*; D008892:Milk / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins