ABSTRACT Objective The purpose of this study was to investigate the pharmacokinetic alterations of flunixin and tolfenamic acid in experimental endotoxemic sheep. Methods 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. Results 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. Conclusions 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.
Altınok-Yi̇pel et al. (Fri,) studied this question.