Pharmacokinetics and tissue residues of colistin following intravenous, and single and repeated oral dosing in domestic geese (Anser anser domesticus)

Abstract

Colistin, also known as polymyxin E, is a member of the polymyxin group of antibiotics. It is approved in Europe to treat enteric infections caused by Gram-negative bacteria, such as Escherichia coli, in poultry, although the similarity of infections between species make it likely used off-label in geese as well.This study investigated the pharmacokinetics and tissue residues of colistin in geese through in vivo experiments. The study involved longitudinal open studies on 16 healthy adult male geese, divided into three phases separated by one-month washout period. Geese were administered colistin via intravenous (IV, 1 mg/kg), single oral (PO, 30 mg/kg), and multiple oral (SID, 2.5 mg/kg for five consecutive days) routes, with blood samples drawn at specific intervals. Tissue samples were also collected at pre-assigned times for subsequent analysis. Colistin levels in geese plasma were quantified using a fully validated UHPLC-MS/MS method.

Plasma concentrations could be quantified up to 24 h for the single PO (n= 2) and IV (n= 4) routes, and up to 10 h (n= 6) from the last dose administered for the multiple PO route (n=6). The bioavailability was significantly low, averaging 3 %. The terminal half-life in geese was 2.18 h following IV administration, similar to values found in other avian species. Following IV administration, clearance and volume of distribution values were 0.11 mL⋅h⁻¹⋅g⁻¹ and 0.41 mL⋅g⁻¹, respectively. The body extraction ratio was low at 0.2 %, indicating minimal hepatic and renal elimination of colistin. Multiple oral doses showed no plasma accumulation, and tissue levels consistently remained below the maximum residue limit (MRL) set for food-producing animals. This study highlights the minimal systemic bioavailability and tissue penetration of colistin in geese, consistent with findings in other poultry and mammals. Future research should focus on intestinal colistin content in geese to optimize dosing strategies and minimize anti-microbial resistance.