In this study, the pharmacokinetics of ceftriaxone (40 mg/kg) was determined following a single intravenous (IV) administration of ceftriaxone alone and co-administration with ketoprofen (3 mg/kg) or tolfenamic acid (2 mg/kg) in sheep. Eight healthy Akkaraman sheep (2.4 ± 0.3 years and 44 ± 4 kg of body weight) were used. The study was carried out according to the longitudinal design in three periods with a 15-day washout period between administrations. In the first period, sheep received ceftriaxone alone via an IV injection. In the second and third periods, the same sheep received ceftriaxone in combination with ketoprofen and tolfenamic acid, respectively. Plasma concentrations of ceftriaxone were assayed by high-performance liquid chromatography and analyzed using non-compartmental analysis. Following the administration of ceftriaxone alone, the elimination half-life (t_1/2ʎz), area under the plasma concentration–time curve from zero (0) hours to infinity (∞) (AUC_0-∞), total clearance (Cl_T), and volume of distribution at steady state were 1.42 h, 182.41 h*µg/ml, 0.22 L/h/kg, and 0.17 L/kg, respectively. While ketoprofen and tolfenamic acid significantly increased the t_1/2ʎz and AUC_0-∞ of ceftriaxone, they significantly reduced the Cl_T. Ceftriaxone (40 mg/kg, IV) in concurrent use with ketoprofen and tolfenamic acid can be administrated at the 12 h dosing intervals to maintain T> minimum inhibitory concentration (MIC) values above 60% in the treatment of infections caused by susceptible pathogens with the MIC value of ≤0.75 and ≤1 μg/mL, respectively, in sheep with an inflammatory condition.

中文翻译：

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酮洛芬和托芬那酸对头孢曲松在绵羊静脉内药代动力学的影响

在这项研究中，头孢曲松 (40 mg/kg) 的药代动力学是在头孢曲松单独静脉 (IV) 给药并与酮洛芬 (3 mg/kg) 或托芬那酸 (2 mg/kg) 共同给药后在绵羊身上测定的. 使用了八只健康的 Akkaraman 绵羊（2.4 ± 0.3 岁和 44 ± 4 kg 体重）。该研究是根据纵向设计分三个时期进行的，给药之间有 15 天的清除期。在第一阶段，绵羊通过静脉注射单独接受头孢曲松。在第二和第三阶段，同一只羊分别接受了头孢曲松联合酮洛芬和托芬那酸。通过高效液相色谱法测定头孢曲松的血浆浓度并使用非房室分析进行分析。单独服用头孢曲松后，t _1/2ʎz )、血浆浓度-时间曲线下面积从零 (0) 小时到无穷大 (∞) (AUC _0-∞ )、总清除率 (Cl _T ) 和稳态分布容积为 1.42 h，分别为 182.41 h*µg/ml、0.22 L/h/kg 和 0.17 L/kg。虽然酮洛芬和托芬那酸显着增加了头孢曲松的 t _1/2ʎz和 AUC _0-∞，但它们显着降低了 Cl _T. 头孢曲松 (40 mg/kg, IV) 与酮洛芬和托芬那酸同时使用，可在 12 小时给药间隔内给药，以维持 T> 最小抑制浓度 (MIC) 值高于 60%，用于治疗敏感病原体引起的感染炎症状态绵羊的MIC值分别≤0.75和≤1 μg/mL。