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Depletion of moxidectin tissue residues in sheep
A Lifschitz1, F Imperiale, G Virkel
1Laboratorio de Farmacologia, Dpto. de Fisiopatologia, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro, Campus Universitario, 7000 Tandil, Argentina.
Abstract:
The pattern of tissue depletion of moxidectin (MXD) subcutaneously administered to sheep was characterized in this study. MXD concentration profiles were determined in muscle, fat, and liver and at the site of injection following administration of a formulation combining MXD (0.5% w/v) with a standard 6 in 1 clostridial vaccine. Thirty-five (35) parasite-free Lincoln sheep were treated with the MXD injectable formulation at a dose rate of 0.2 mg of MXD/kg of live weight, administered subcutaneously on the inner surface of the thigh. Treated animals were sacrificed in randomly selected groups of six sheep weekly from day 21 until day 49 post-treatment. Three nontreated animals were sacrificed to obtain blank tissue samples to validate the analytical methodology. MXD concentration profiles were determined by a validated HPLC analytical method using fluorescence detection. MXD has an adequate pattern of absorption, based on the low residual concentrations found in the injection site area at all sampling intervals. Muscle samples showed the lowest MXD concentrations throughout the study period. The highest MXD concentrations at all sampling times were measured in the adipose tissue, indicating that fat is a target tissue for MXD. MXD concentrations in all of the tissues analyzed were below the accepted maximum limit of residue at 21 days post-treatment.
Insights
Moxidectin (MXD) administered subcutaneously to sheep showed adequate absorption, with fat as a target tissue. Residual MXD levels in all tissues were below maximum limits by 21 days post-treatment.
Area of Science:
- Veterinary Pharmacology
- Parasitology
- Pharmacokinetics
Background:
- Moxidectin (MXD) is a widely used antiparasitic agent in livestock.
- Understanding tissue distribution and depletion is crucial for establishing withdrawal periods and ensuring food safety.
- Co-administration with vaccines requires evaluation of drug behavior in target animal species.
Purpose of the Study:
- To characterize the tissue depletion pattern of moxidectin (MXD) following subcutaneous administration in sheep.
- To determine MXD concentration profiles in muscle, fat, liver, and injection site tissue.
- To assess the adequacy of absorption and establish residue levels over time.
Main Methods:
- Subcutaneous injection of MXD formulation (0.5% w/v) at 0.2 mg/kg in Lincoln sheep.
- Weekly tissue sampling (muscle, fat, liver, injection site) from day 21 to 49 post-treatment.
- Quantification of MXD concentrations using a validated High-Performance Liquid Chromatography (HPLC) method with fluorescence detection.
Main Results:
- Adequate absorption indicated by low residual concentrations at the injection site.
- Fat tissue exhibited the highest MXD concentrations, identifying it as a target tissue.
- Muscle tissue showed the lowest MXD concentrations throughout the study.
- All analyzed tissues demonstrated MXD concentrations below the maximum residue limit (MRL) by 21 days post-treatment.
Conclusions:
- Subcutaneous moxidectin administration in sheep results in favorable absorption and distribution patterns.
- Adipose tissue serves as a primary reservoir for moxidectin in sheep.
- A 21-day post-treatment interval is sufficient to ensure moxidectin residues are below established safety limits in sheep tissues.