Pharmacokinetics of veterinary drugs in laying hens and residues in eggs: a review of the literature V. GOETTING K. A. LEE & L. A. TELL Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, USA Goetting, V., Lee, K. A., Tell, L. A. Pharmacokinetics of veterinary drugs in laying hens and residues in eggs: a review of the literature. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2011.01287.x. Poultry treated with pharmaceutical products can produce eggs contaminated with drug residues. Such residues could pose a risk to consumer health. The following is a review of the information available in the literature regarding drug pharmacokinetics in laying hens, and the deposition of drugs into eggs of poultry species, primarily chickens. The available data suggest that, when administered to laying hens, a wide variety of drugs leave detectable residues in eggs laid days to weeks after the cessation of treatment. (Paper received 10 September 2010; accepted for publication 12 February 2011) Lisa A. Tell, Department of Medicine and Epidemiology, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA. E-mail: latell@ucdavis INTRODUCTION In poultry, antibiotics and antiparasitics are used extensively for disease prevention and treatment. In the United States, antibiotics are also used for growth promotion, although this type of use has been prohibited in the European Union since 2006 (Donoghue, 2003; Castanon, 2007; Companyo et al., 2009). Edible tissues containing veterinary drug residues can pose risks to human health, including direct toxic effects, allergic reactions and increased bacterial resistance to common antibiotics (Botsoglou & Fletouris, 2001; Donoghue, 2003; Companyo et al., 2009). Drug residues in chicken eggs are of concern because relatively few drugs are labelled for laying hens, although several medications are approved for other production classes of poultry (Hofacre, 2006; Castanon, 2007). Drug residues in eggs may arise when laying hens are mistakenly given medicated feed, when feed is contaminated at the mill during mixing, or when drugs are given off-label (Kennedy et al., 2000; Donoghue, 2003). While a chicken lays an egg roughly every 24 h, each egg takes several days to develop in vivo, and some egg components are in existence months before the fully developed and shelled egg containing them is laid (Etches, 1996; Whittow, 2000). Because of the protracted nature of egg development, many weeks may be required following treatment or exposure before eggs are free of drug residues. It should be noted that some drugs included in this review are prohibited from use in some or all food animals in the US and ⁄ or the EU. In the US, extra-label use of fluoroquinolones is prohibited in food animals, and any use of these drugs in a manner not explicitly approved is illegal. If an animal is mistakenly or intentionally treated with a drug that is prohibited from extra-label drug use, then the exposed animal(s) should not enter the food chain unless permission is granted from the proper authorities. In both the US and EU, other drugs, including chloramphenicol, the nitroimidazoles, and nitrofurans, are completely prohibited from use in food animals (Davis et al., 2009; EMEA, 2009). A summary of drugs approved in the US for game bird species has been published (Needham et al., 2007), and a recent update on drugs prohibited from extra-label drug use in the US is available (Davis et al., 2009). EU approval statuses and maximum residue limits for veterinary drugs used in food-producing animals are described in the European Commission Regulation 37 ⁄ 2010 (European Commission, 2009). Of the three main egg components (yolk, albumen, and shell), the yolk has the longest development time. Precursors to yolk lipoproteins are produced in the liver and transported through circulation to the yolk follicles in the ovary. In an actively laying hen, several follicles at varying developmental stages reside simultaneously in the ovary. Before an egg is laid, the yolk undergoes a stage of rapid growth, in which it increases in size exponentially over 10 days (Etches, 1996). Drugs that deposit in the yolk will rapidly accumulate during this time and can be present in successive eggs for 10 or more days following treatment. Following yolk maturation, the albumen or ‘egg white’ is laid down over a period of 2–3 h (Whittow, 2000) and can also serve as a residue accumulation site. The egg shell is added after albumen proteins are deposited and diluted with water (Etches, 1996). The egg development process is similar across species of poultry and game birds, although the rates of development vary (Whittow, 2000). A detailed diagram of a chicken egg is shown in Fig. 1. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2011.01287.x REVIEW ARTICLE Ó 2011 Blackwell Publishing Ltd 1