Pharmacokinetics of Hetacillin in Dairy Cattle Following 3X Milking

Recipient Organization
NORTH CAROLINA STATE UNIV
(N/A)
RALEIGH,NC 27695

Performing Department
Population Health and Pathobiology

Non Technical Summary
Hetacin-K is currently approved as a once a day intramammary treatment for cows with mastitis and can be used for a total of 3 days. Although this drug has been marketed for quite a few years, there is very little scientific data published on hetacillin. More and more dairy farms are milking 3 times per day and we have very little pharmacokinetic data on the use of intramammary drugs in a 3X system. Particularly with a drug like Hetacin-K that is dosed only once per day - it needs to be verified that therapeutic concentrations can be maintained for a 24-hour period. We believe the data from this part of the study will be relevant to the dairy industry and will help the BIVI veterinary staff better council veterinarians on the proper use of Hetacin-K on farms milking three times per day. In addition - we have been unable to find any published pharmacokinetic data on the pharmacokinetics of hetacillin in dairy cows. Surely studies were done for the original approval of the drug - however this data is old and very difficult to locate. The data generated in this study will also be helpful to dairy farms milking twice a day as we will get a better idea of ampicillin concentrations remaining in the quarter at 8, 16 and 24 hours after drug administration.

Animal Health Component

50%

Research Effort Categories

Basic

50%

Applied

50%

Developmental

(N/A)

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
712	3440	1180	100%

Knowledge Area
712 - Protect Food from Contamination by Pathogenic Microorganisms, Parasites, and Naturally Occurring Toxins;

Subject Of Investigation
3440 - Meat, dairy cattle;

Field Of Science
1180 - Pharmacology;

Keywords

Goals / Objectives
To determine if once a day intramammary infusion of Hetacin-K is sufficient to maintain therapeutic drug concentrations in cattle milked 3 times per day.

Project Methods
This study will be done at the North Carolina State University Dairy, a modern dairy that milks approximately 200 cows. Cows will not have been treated for mastitis during their present lactation to be eligible for the study. After collecting a baseline milk sample, 8 Holstein cows will receive intramammary infusions of Hetacin-K® in the left front and right rear quarters once a day for 3 days (following label instructions). Each of these cows will be milked 3 times per day throughout the study period. Composite samples representing milk from each of the treated quarters will be collected at each milking (using a quarter sampling system) and frozen until analysis. We will collect milk for an additional 3 days following completion of the intramammary infusions in order to model the elimination phase of hetacillin excretion. Milk samples from treated quarters will be analyzed for ampicillin concentrations using a UPLC method (we will not analyze milk samples from untreated quarters). Hetacllin is prepared by a reaction of hetacillin with acetone. When administered as an aqueous solution, hetacillin is rapidly converted back to ampicillin and acetone. Therefore by measuring milk amipicillin concentrations, we should get an accurate representation of antimicrobial concentrations in the milk resulting from Hetacin-K® administration. The primary purpose of this study is to determine whether once a day dosing of hetacillin is sufficient to maintain therapeutic drug concentrations in milk for a 24-hour period in cows that are being milked three times per day. By infusing hetacillin into 2 quarters in 8 different cows, this will allow us to model data from 16 different treatments - thus significantly increasing the power of the study as compared to infusing only one quarter per cow.

Progress 09/26/13 to 06/30/14

Outputs
Target Audience: Industry Sponsor- Boehringer Ingelhelm Vetmedica, Inc.; Dairy Cattle Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Provided research supplies and services. The student was mentored by Dr. Geof Smith in setting up the experimental design, ampicillin assay, and reporting the results to the sponsor. How have the results been disseminated to communities of interest? Final report was submitted to BIVI. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Study Conclusions Hetacin-K 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 three times per day. There is no reason the drug should be administered at more frequent intervals. The approved withdrawal time of 72 hours would still apply for cows milked 3 times per day. However our data would suggest cows milked more frequently are eliminating ampicillin at a faster rate than traditional cows milked twice/day.

Publications