Pharmacokinetics of long-acting cephapirin and cloxacillin after intramammary administration in dairy goats

Abstract

Determining the pharmacokinetics of intramammary antimicrobials in goats can assist in predicting appropriate meat and milk withdrawal intervals for drugs that are effective at treating subclinical mastitis due to non-aureus Staphylococci during the dry period. Twenty-four healthy, lactating does were enrolled in this study. Half were administered 300 mg of cephapirin benzathine (ToMORROW, Boehringer Ingelheim Vetmedica, Duluth, GA) via intramammary infusion into each half of the udder. The remaining does had 500 mg cloxacillin benzathine (Orbenin DC, Merck & Co., Rahway, NJ) administered per half. Plasma was collected before treatment and for 7 days post-treatment followed by analysis via liquid chromatography with tandem mass spectroscopy. Pharmacokinetic parameters were determined using noncompartmental methods via commercial software (MonolixSuite). The mean maximum concentration (C _max) of cephapirin of 0.073 μg/mL was noted at 7.06 h post-administration (T _max). The area under the plasma concentration curve based on the final sampling point (AUC_last) was 1.06 h × μg/mL. The mean residence time until the final sampling point (MRT_last) was 13.55 h. Mean terminal half-life (T _½) of cephapirin was 6.98 h. In CLOX does, C _max was 0.074 μg/mL with a T _max of 18 h, AUC_last was 5.71 h × μg/mL, T _½ was 77.45 h, and MRT_last was 65.36 h. Despite both products being formulated with benzathine salts, marked differences were noted in pharmacokinetic parameters including AUC, T _1/2, and MRT_last. This data will be used to plan sampling schedules for milk and tissue residue depletion studies for both products.