Pharmacokinetics of colistin sulfate and berberine sulfate following intramuscular injection as single agents or in combination in swine

Abstract With the increasing prevalence of drug resistance from antibiotic abuse, bacterial diseases pose a serious threat to the livestock farming industry and public health. This study aimed to investigate and compare the pharmacokinetic profiles of the combined injection comprising colistin sulfate–berberine sulfate and its individual components (colistin sulfate and berberine sulfate) in swine. The combined injection was administered either intramuscularly at doses of 0.5, 1.0, 2.0, and 4.0 mg/kg or intravenously at a dose of 1.0 mg/kg, while single-agent injections were administered intramuscularly at a dose of 2.0 mg/kg. Colistin sulfate and berberine sulfate concentrations in plasma were quantified via ultra-performance liquid chromatography‒tandem Mass spectrometry, and the pharmacokinetic parameters were analyzed via a noncompartmental analysis model. A Linear mixed-effect model was used for the combined injection within the 0.5–4.0 mg/kg range. At the 2.0 mg/kg intramuscular dose, the combination injection produced higher maximum concentration for colistin sulfate (7.00 ± 2.18 μg/mL) and berberine sulfate (3.36 ± 1.04 μg/mL) than the single-agent injections (4.37 ± 0.72 and 1.44 ± 0.32 μg/mL, respectively). Following the combined injection of 0.5, 1.0, 2.0, or 4.0 mg/kg and the single-agent injections of 2.0 mg/kg, the corresponding absolute bioavailabilities were 48.00%, 52.05%, 79.04%, 82.40%, and 77.52%, respectively, for colistin sulfate and 2.98%, 6.81%, 10.49%, 11.35%, and 8.00%, respectively, for berberine sulfate. Furthermore, the combined injection showed dose proportionality following intramuscular administration across the tested dose range for both colistin sulfate and berberine sulfate. Our research findings provide a theoretical basis for the precise clinical use of this drug combination in veterinary medicine and ensure the safety of animal-derived food and public health. Further research is warranted to explore its efficacy and safety in clinical settings.