title: Short communication: Pharmacokinetics of intramammary hetacillin in dairy cattle milked 3 times per day.
abstract: Mastitis remains a critical disease in the dairy industry and the use of intramammary antibiotics plays a critical role in mastitis treatment. Hetacillin is currently approved as an intramammary antibiotic that is used to treat mastitis in dairy cows. It is approved for once a day administration and can be used for a total of 3 d. An increasing number of dairy farms are milking 3 times per day (instead of the traditional 2 times per day) and very little pharmacokinetic data exists on the use of intramammary drugs in a 3×system. The primary purpose of this study was to determine if once a day intramammary infusion of hetacillin is sufficient to maintain therapeutic drug concentrations in cattle milked 3 times per day. Eight Holstein cattle milked 3 times per day were used in this study. After collecting a baseline milk sample, each cow received intramammary infusions of hetacillin in the left front and right rear quarters once a day for 3 d. Milk samples from each of the treated quarters were collected at each milking and frozen until analysis. Milk samples were analyzed for ampicillin concentrations using an ultra-performance liquid chromatography method. All treated quarters had antibiotic concentrations well above the minimum inhibitory concentration (MIC) for gram-positive mastitis pathogens at 8 and 16 h postinfusion. Milk concentrations had fallen well below the MIC by the 24-h period (before the next infusion). All 8 cows in this study consistently had individual quarter milk ampicillin concentrations below the FDA tolerance of 0.01 μg/mL (10 ppb) within 48 h of the last infusion. Based on this study, milk ampicillin concentrations exceed the minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC90) for at least 65% of the dosing interval, which is sufficient for once-daily dosing with most cases of gram-positive mastitis. Therefore, intramammary hetacillin should be an effective treatment for the vast majority of gram-positive mastitis pathogens when used according to label (once per day) in cows milked 3 times per day.
authors.affiliation: Department of Population Health and Pathobiology and the Food Animal Residue Avoidance Depletion Program, College of Veterinary Medicine, North Carolina State University, Raleigh 27607.
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Lindquist
authors.affiliation: Department of Population Health and Pathobiology and the Food Animal Residue Avoidance Depletion Program, College of Veterinary Medicine, North Carolina State University, Raleigh 27607.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Baynes
authors.affiliation: Department of Population Health and Pathobiology and the Food Animal Residue Avoidance Depletion Program, College of Veterinary Medicine, North Carolina State University, Raleigh 27607. Electronic address: Geoffrey_Smith@ncsu.edu.
authors.forename: Geof W
authors.initials: GW
authors.lastname: Smith
mesh_terms: D000667:Ampicillin / Q000032:analysis; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002417:Cattle / Q000378:metabolism*; D003612:Dairying / Q000379:methods; D005260:Female; D007774:Lactation; D008321:Mammary Glands, Animal / Q000187:drug effects; D008414:Mastitis, Bovine / Q000188:drug therapy; D008826:Microbial Sensitivity Tests; D008892:Milk / Q000737:chemistry; D010406:Penicillins / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D010406:Penicillins; D000667:Ampicillin; C100115:hetacillin
keywords: hetacillin; intramammary; mastitis; pharmacokinetics