Estimation of the Withdrawal Time of Levamisole in Eggs after Oral Administration to Laying Hens

Abstract

This study was conducted to evaluate withdrawal time of levamisole in eggs after oral administration in laying hens at different doses. Sampling of eggs was conducted for 37 days after the end of treatment, and levamisole concentrations were measured by liquid chromatography-tandem mass spectrometry validated according to the Commission Decision 2002/657/EC. Estimated validation parameters were as follows: decision limit, 0.54 μg/kg; detection capability, 0.56 μg/kg; limit of detection, 0.04 μg/kg; limit of quantification, 0.15 μg/kg; accuracy (recovery), between 92.9 and 102.3%; precision (relative standard deviation), ≤4.62%; and within-laboratory precision (relative standard deviation), ≤5.19%. Levamisole residue levels were significantly higher in egg yolks than in egg whites. The highest levels of levamisole were detected on day 2 posttreatment in groups receiving 50 mg/kg of body weight (556.2 μg/kg in egg yolks and 166.5 μg/kg in egg whites). Significant elimination occurred within 5 days after the cessation of treatment in all groups, with an elimination half-life of 1.3 days. Levamisole was still detectable on day 30 after the end of treatment in egg whites (0.06 μg/kg) and on day 37 in egg yolks (0.06 μg/kg). The longest withdrawal time for levamisole in eggs (14.9 days) was determined in a group treated with 25 mg of levamisole per kg of body weight for two consecutive days. According to the results, oral treatment of laying hens with levamisole may result in noncompliant egg samples even 14 days after treatment.

Pharmacokinetic profiles and egg residue patterns of levamisole in laying hens at two dosing rates and two routes of administration

“…Kolanović et al suggest 17.2 d of withdrawal time for LEV in eggs after 25 mg/kg of PO LEV administration for 2 consecutive days under below the limit (0.025 mg/kg), which is 2.5 times higher than the PLS (0.01 mg/kg), and El-Kholy and Kemppainen report a 9-d withdrawal period for eggs after 40 mg/kg of single PO LEV under 0.1 mg/kg limit, which is 10 times higher than the PLS standard ( El-Kholy and Kemppainen, 2005 ; Kolanović et al, 2018 ). Several factors may affect withdrawal period determination, including the type of analytical device, treatment dose, and MRL level designated.…”

“…LEV is recognized as a biopharmaceutical classification system ( BCS ) class 1 drug that is readily absorbed from the gastrointestinal tract and excreted in urine after being metabolized by the liver ( Kouassi et al, 1986 ; Kolanović et al, 2018 ; del Moral-Sanchez et al, 2019 ).…”

“…LEV is highly effective in controlling gastrointestinal and pulmonary nematodes ( Sahagún et al, 2000 ). In poultry, it is used to treat ascariasis, one of the most prevalent parasitic diseases and about 30 mg/kg reported to be effective in chicken ( Kolanović et al, 2018 ; Feyera et al, 2021 ). However, it has not been approved by the FDA for use in poultry and the limited data on pharmacokinetics and withdrawal time available ( El-Kholy et al, 2006 ).…”

“…However, it has not been approved by the FDA for use in poultry and the limited data on pharmacokinetics and withdrawal time available ( El-Kholy et al, 2006 ). Moreover, the use of LEV in egg-laying hens for human consumption is prohibited ( Kolanović et al, 2018 ).…”

Anthelmintics for drug repurposing: Opportunities and challenges

“…Levamisole is metabolized in the liver and kidney into several components, such as aminorex, and mostly excreted via the kidneys. Depending on the animal species, it has a plasma elimination half-life of 5–6 h ( Handley et al, 2019 , Kolanović et al, 2018 ). Pyrantel is mostly metabolized into metabolites with higher polarity in various animals through different metabolic pathways, including the oxidation of the thiophene ring, the oxidation of the tetra-pyrimidine ring, and conjugation to mercapturic acid.…”