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.

Development and Validation of a UPLC-MS/MS Method to Monitor Cephapirin Excretion in Dairy Cows following Intramammary Infusion

“…Also, with time, conversion of cephapirin to its major metabolite desacetyl cephapirin is likely. Within 24 h of intramammary infusion of cephapirin in lactating cows >50% of infused cephapirin was converted to desacetyl cephapirin [3], [48].…”

Short communication: Pharmacokinetics of intramammary hetacillin in dairy cattle milked 3 times per day

“…According to data from the 2007 NAHMS survey, more than 92.5% of dairy operations milk cows twice a day (USDA-APHIS, 2008). However, a growing number of dairy producers are increasing their milking frequency from twice to 3 times per day (3×) to improve milk production (Pearson et al, 1979;Smith et al, 2002;Hale et al, 2003). When producers treat mastitis in cows milked 3×, it is difficult to know what the proper dosing interval for intramammary antibiotics should be to maintain adequate therapeutic drug concentrations in the mammary gland.…”

“…Therefore, from a clinical view, it is critical to generate pharmacokinetic data on intramammary antibiotics in cattle milked 3× to help determine appropriate dosing intervals for producers. Past studies demonstrated that milking frequency did not affect the length of time that milk drug concentrations exceeded the MIC values when intramammary cephapirin was administered to dairy cows (Stockler et al, 2009a;Gorden et al, 2013). However, no data exist on the pharmacokinetics of intramammary hetacillin in dairy cattle.…”

Elimination kinetics of ceftiofur hydrochloride in milk after an 8-day extended intramammary administration in healthy and infected cows

“…For bovine mastitis episodes caused by highly contagious staphylococci or streptococci, an intramammary infusion (IMM) of antimicrobial agents is usually used to treat clinical mastitis[ 4 , 5 ]. This treatment has been confirmed as having a good therapeutic effect as an antimicrobial agent, and it can attain and maintain an adequate and effective drug concentration at the site of infection in mammary tissue [ 6 , 7 ]. Ceftiofur is a broad-spectrum, third-generation cephalosporin antibiotic for veterinary use.…”