Does anatomical location affect the pattern of drug residues in muscle? Evaluation of ivermectin (sheep) and doramectin (cattle) residues in muscular tissue

MORENO, L; CEBALLOS, L; ALVAREZ, L; SANCHEZ BRUNI, S; LANUSSE, C

Torino, Italia

Congreso; 10th International Congress of the European Association for Veterinary Pharmacology and Toxicology; 2006

Does anatomical location affect the pattern of drug residues in muscle? Evaluation of ivermectin (sheep) and doramectin (cattle) residues in muscular tissue L. Moreno; L. Ceballos; L. Alvarez; S. Sánchez Bruni and C. Lanusse Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro, Tandil, Argentina.   Introduction: Veterinary drugs are widely used to protect animal health, prevent production loss and to ensure a safe food supply. The fate of chemical residues from veterinary drugs in animal tissues destined to human consumption is a pivotal issue for food safety. To reach the required food protection level, reliable data must be available to permit adequate risk evaluation and subsequent action. Ivermectin (IVM) and doramectin (DRM) are lipophilic avermectin compounds extensively used for broad-spectrum parasite control in food-producing animals. Both molecules are extensively distributed from the bloodstream to different body tissues, including fat, muscle and liver tissues (1). Adipose and other edible fat-containing tissues are important tissue reservoir for the avermectin and related compounds in ruminants, which accounts for their extended persistence antiparasitic activity. Muscular tissue in food-producing animals may present different fat infiltration grade, with variable blood supply according to its anatomical location and physiological role. Thus, the pattern of residues distribution for highly lipophilic drugs could be variable in muscular tissue from different anatomical areas. Considering that meat is the main edible tissue destined to human consumption, the current work provides some tissue residue kinetic data for widely livestock used compounds, which may result useful to assure food safety. The trial presented here characterized the comparative drug residual concentrations in muscular tissue obtained from different anatomical locations after subcutaneous administration of IVM (sheep) and topical treatment with DRM (calves) at recommended therapeutic dose rates.   Materials and Methods: Two parallel experiments were carried out. Animals received food and water ad libitum during the whole experimental period. Exp. 1 “Residues in sheep”: Twelve (12) adult male Corriedale sheep (49.4 ± 7.93 kg) were subcutaneously treated with a commercial formulation of IVM at 200 µg/kg. Exp 2 “Residues in Cattle”: Twelve (12) Holstein calves (180 ± 30.9 kg) were treated with a commercial formulation of DRM by topical (pour-on) administration at the recommended dose rate (500 µg/kg). In both experiments, four animals were randomly assigned for sacrifice at: 15, 20 and 30 days post-treatment (Exp 1) and at 2, 5 and 10 days post-treatment (Exp 2). Animals were sacrificed according to ethic animal euthanasia guidelines (2). Muscle samples from the following anatomical regions were collected at the above indicated sampling times: neck, shoulder, thigh (semitendinosus), rump, loin, inter-costal and diaphragm. They were collected and processed (1 g) as previously reported (1). DRM and IVM were determined by HPLC using fully validated analytical techniques (1). ANOVA plus Tuckey Test was used for statistical comparisons. Results: The highest IVM residual concentrations in all the muscle locations were found at 15 days post-treatment in   sheep. Although the highest IVM mean concentrations were measured at 15 (16.8±10.3 ng/g) and 20 (10.5±7.0 ng/g) days post-administration at the intercostals muscles, the highest IVM residues (4.91±5.2 ng/g) at 30 days post-administration were measured at the diaphragmatic area. DRM residual concentrations were quantified in muscular tissue from all the anatomical locations after the topical administration to calves (Table 1). The maximum residue level was determined at 10 days post-treatment in all the anatomical sites. The diaphragm area showed the highest DRM reside levels at 2, 5 and 10 days post-treatment in calves.   Discussion and Conclusions: While the highest IVM residual levels were measured in the inter-costal muscles in sheep, the diaphragm was the muscle where the highest DRM residues were recovered in topically-treated cattle. The observed tendency on differential residue patterns among anatomical sites for both molecules did not reached statistically significant differences (P>0.05) due to large individual variability in the concentration values. However, the pattern of IVM and DRM residues depletion from the muscular tissue seems to differ according to the anatomical location and/or physiological role. Regardless the preliminary data shown here, this work is part of a broader study in which several conflictive issues related to chemical residues in edible tissues are under evaluation: a) assessment of tissue residues at the site of injection, including criteria for sample collection and drug diffusion into the hypodermic and muscular tissue surrounding the injection area, and b) the use of tissue biopsy as a technique to obtain valid information on residue profiles in treated animals.