The Impact of Ketoprofen on the Pharmacokinetics of Marbofloxacin at Variable Intravenous Doses in Sheep

The objective of this study was to determine the effect of ketoprofen (3 mg/kg, IV) on the pharmacokinetics of marbofloxacin administered intravenously at 2 and 10 mg/kg in sheep, and to identify possible changes in key pharmacokinetic parameters when combined. Twelve healthy Merino sheep were enrolled in a two‐stage crossover pharmacokinetic study. Each animal received intravenous marbofloxacin at 2 and 10 mg/kg, administered either alone or in combination with ketoprofen (3 mg/kg, IV). Blood samples were collected over 48 h, and plasma marbofloxacin levels were measured using HPLC‐UV. Pharmacokinetic parameters were calculated by non‐compartmental analysis. Compared to the 2 mg/kg dose, the AUC and t 1/2ʎz increased and Cl T decreased at the 10 mg/kg dose of marbofloxacin ( p < 0.05). Combination administration with ketoprofen decreased Cl T and Vd ss values in both dose groups, and increased AUC and t 1/2ʎz values ( p < 0.05). Ketoprofen significantly alters marbofloxacin's pharmacokinetic parameters, increasing its systemic exposure. It is thought that the increased AUC, especially with high‐dose or combined administration, may enhance antibacterial efficacy by raising the AUC/MIC ratio. Potential drug interactions should be considered in clinical practice.