Pharmacokinetics and pharmacodynamics of single and multiple-dose levamisole in belugas (Huso huso): Main focus on immunity responses.

The pharmacokinetics of levamisole were determined in the belugas after single intravascular (IV), and single and multiple-dose oral by feed administrations. Also, the effect of levamisole (LVM) on the stress and immune responses of belugas were assessed. One hundred-fourteen healthy belugas in 4 different groups received single LVM administration at the doses of 50 and 100 mg/kg via IV and oral routes. A separate group of 24 belugas were administered oral LVM at the dose of 100 mg/kg for 5 days. Blood samples were collected at different time points after administrations to measure plasma concentrations of LVM by a validated high-performance liquid chromatography (HPLC) assay. For immunological evaluations, a total of 126 belugas received 50 and 100 mg/kg LVM via medicated feed for 5 days or served as the control without any medication; blood samples were recovered on day 0, 1, 3, 5, 7, 10, and 14 to measure hemolytic activity of the complement system (HAC), serum lysozyme activity, serum antibacterial activity, glucose, cortisol, total protein, albumin and C3 contents. In the single-dose administration, quantified LVM concentrations were dose-dependent and the oral bioavailability was in the range of 43.2-49.6%. In the multiple-dose administration, the peak plasma concentration at the steady state was 45.2 mg/ml, and accumulation ratio was calculated as 3.6. In the immunological study, LVM especially at the dose of 100 mg/kg increased HAC, lysozyme and antibacterial activity in the sera of treated fish. No significant effect of LVM on glucose and albumin content was observed, but cortisol levels decreased and C content was increased, more significantly by LVM at the dose of 100 mg/kg. Our results indicate that LVM is well absorbed after oral administration and reached to concentrations that can affect stress indicators and improve immune responses in belugas.