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ARS Home » Plains Area » Fargo, North Dakota » Red River Valley Agricultural Research Center » Animal Metabolism-Agricultural Chemicals Research » Research » Publications at this Location » Publication #322146

Research Project: METABOLIC FATE OF CHEMICAL AND BIOLOGICAL CONTAMINANTS

Location: Animal Metabolism-Agricultural Chemicals Research

Title: Distribution of animal drugs between skim milk and milk fat fractions in spiked whole milk: Understanding the potential impact on commercial milk products

Author
item Hakk, Heldur
item Shappell, Nancy
item Lupton, Sara
item Shelver, Weilin
item Fanaselle, Wendy - U.s. Food & Drug Administration (FDA)
item Oryang, David - U.s. Food & Drug Administration (FDA)
item Yeung, Chi Yuen - U.s. Food & Drug Administration (FDA)
item Hoelzer, Karin - U.s. Food & Drug Administration (FDA)
item Ma, Yinqing - U.s. Food & Drug Administration (FDA)
item Gaalswyk, Dennis - U.s. Food & Drug Administration (FDA)
item Pouillot, Regis - U.s. Food & Drug Administration (FDA)
item Van Doren, Jane - U.s. Food & Drug Administration (FDA)

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/10/2015
Publication Date: 1/1/2016
Publication URL: http://handle.nal.usda.gov/10113/61801
Citation: Hakk, H., Shappell, N.W., Lupton, S.J., Shelver, W.L., Fanaselle, W., Oryang, D., Yeung, C., Hoelzer, K., Ma, Y., Gaalswyk, D., Pouillot, R., Van Doren, J.M. 2016. Distribution of animal drugs between skim milk and milk fat fractions in spiked whole milk: Understanding the potential impact on commercial milk products. Journal of Agricultural and Food Chemistry. 64(1):326-335.

Interpretive Summary: Seven veterinary drugs, representing a broad range of antibiotic, NSAIDs, anthelmintics were used to evaluate the drug distribution between milk fat and skim milk fractions of cow’s-milk. We hypothesized that drugs would distribute into milk fat based on their fat solubility. The drugs that were highly fat soluble did indeed largely concentrate into milk fat to a greater degree than those with a lower fat solubility. However, the relationship between the drug fat solubility and drug distribution suggested that additional factors influence this relationship, such as the presence of proteins. The ultimate intent of this research was the development of an experimental data-based model. This research provided candidate models that can be used to predict the distribution of other drugs and drug metabolites in milk and milk products.

Technical Abstract: Seven animal drugs [penicillin G (PENG), sulfadimethoxine (SDMX), oxytetracycline (OTET), erythromycin (ERY), ketoprofen (KETO), thiabendazole (THIA) and ivermectin (IVR)] were used to evaluate drug distribution between milk fat and skim milk fractions of cow milk. Greater than 90% of radioactivity was distributed into the skim milk fraction for ERY, KETO, OTET, PENG, and SDMX, approximately 80% for THIA, and 13% for IVR. The distribution of drug between milk fat and skim milk fractions was significantly correlated to the drug’s lipophilicity (partition coefficient, log P or distribution coefficient, log D, which includes ionization). Data were fit with linear mixed effects models; best fit was obtained within this dataset with log D versus observed drug distribution ratios. These candidate empirical models serve for assisting to predict the distribution and concentration of these drugs in a variety of milk and milk products.