Elimination kinetics of cephapirin sodium in milk after an 8-day extended therapy program of daily intramammary infusion in healthy lactating Holstein-Friesian cows

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 (200 mg) 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.