title: Elimination kinetics of cephapirin sodium in milk after an 8-day extended therapy program of daily intramammary infusion in healthy lactating Holstein-Friesian cows.
abstract: The objective of this study was to determine the elimination kinetics of extended therapy with intramammary (IMM) cephapirin in lactating dairy cattle. Eight healthy Holstein-Friesian cows were administered cephapirin (200mg) into all 4 mammary glands every 24 h after milking. Cows were milked 3 times per day and concentrations of cephapirin and desacetyl cephapirin were determined in bucket milk using liquid chromatography-mass spectrometry. Milk concentration-time data after the last of the 8 IMM infusions were fitted using compartment and noncompartmental models. The maximum cephapirin concentration was 128±57 µg/mL (mean ± SD), the elimination rate constant from the central compartment was 0.278±0.046 (h(-1)), clearance was 0.053±0.023 L/h, the half time for elimination was 2.55±0.40 h, and the mean residence time was 2.65±0.79 h. The cephapirin concentration was below the approved tolerance in all cows by 96 h after the last infusion, which is the labeled withholding time for the preparation used. Extended therapy for 8 d provided milk cephapirin concentrations above the minimum inhibitory concentration for common gram-positive mastitis pathogens (0.1 to 1.0 µg/mL) for the duration of therapy and for an additional 16 to 32 h after the end of treatment. Our findings suggest that this IMM cephapirin sodium formulation, which is labeled for 2 doses 12 h apart, could be administered at a 24-h interval for up to 8 d in cows milked 3 times per day, with no significant effect on residue levels by 96 h after the last treatment. Longer withdrawal times would be prudent for cows with low milk production.
authors.affiliation: Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, Iowa 50011-1250, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Gorden
authors.forename: M
authors.initials: M
authors.lastname: van der List
authors.forename: F D
authors.initials: FD
authors.lastname: Lehman
authors.forename: R K
authors.initials: RK
authors.lastname: Lantz
authors.forename: P D
authors.initials: PD
authors.lastname: Constable
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002417:Cattle / Q000378:metabolism*; D002514:Cephapirin / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D005260:Female; D007700:Kinetics; D007774:Lactation; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism; D008414:Mastitis, Bovine / Q000188:drug therapy / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D008892:Milk / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D002514:Cephapirin