Pharmacokinetics of Flunixin and Tolfenamic Acid in Experimental Endotoxemic Awassi Sheep

The purpose of this study was to investigate the pharmacokinetic alterations of flunixin and tolfenamic acid in experimental endotoxemic sheep.

The study was conducted on 12 healthy Awassi sheep. The sheep were divided into two equal groups, tolfenamic acid (n = 6) and flunixin (n = 6), and the study in each group was carried out in two stages. The initial stage involved the intravenous (IV) administration of flunixin and tolfenamic acid to healthy sheep at doses of 2.2 mg/kg and 4 mg/kg, respectively. In the second stage, sheep were administered LPS (E. coli O55:B5, 10 µg/kg) followed by IV administration of tolfenamic acid and flunixin. The analysis of drugs was performed using HPLC-UV, and pharmacokinetic parameters were calculated by non-compartmental analysis.

The t_1/2ʎz, Cl_T, and V_dss values were found to be 3.74 h, 0.17 L/h/kg, and 0.54 L/kg for tolfenamic acid and 3.14 h, 0.04 L/h/kg, and 0.12 L/kg for flunixin in healthy sheep, respectively. Both drugs showed longer t_1/2ʎz and MRT_0-∞, higher AUC_0-∞, and lower Cl_T in endotoxemic sheep compared to healthy sheep. The V_dss values of both drugs were similar between healthy sheep and endotoxemic sheep.

The altered pharmacokinetics of flunixin and tolfenamic acid in endotoxemic sheep suggest that dose adjustments and careful therapeutic monitoring are necessary to maintain efficacy and safety.