Altan Feray, Corum Orhan, Yildiz Ramazan, Eser Faki Hatice, Ider Merve, Ok Mahmut, Uney Kamil
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Dicle, Diyarbakir, Turkey.
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Kastamonu, Kastamonu, Turkey.
J Vet Pharmacol Ther. 2020 Mar;43(2):108-114. doi: 10.1111/jvp.12841. Epub 2020 Feb 11.
In this study, the pharmacokinetics of moxifloxacin (5 mg/kg) was determined following a single intravenous administration of moxifloxacin alone and co-administration with diclofenac (2.5 mg/kg) or flunixin meglumine (2.2 mg/kg) in sheep. Six healthy Akkaraman sheep (2 ± 0.3 years and 53.5 ± 5 kg of body weight) were used. A longitudinal design with a 15-day washout period was used in three periods. In the first period, moxifloxacin was administered by an intravenous (IV) injection. In the second and third periods, moxifloxacin was co-administered with IV administration of diclofenac and flunixin meglumine, respectively. The plasma concentration of moxifloxacin was assayed by high-performance liquid chromatography. The pharmacokinetic parameters were calculated using a two-compartment open pharmacokinetic model. Following IV administration of moxifloxacin alone, the mean elimination half-life (t ), total body clearance (Cl ), volume of distribution at steady state (V ) and area under the curve (AUC) of moxifloxacin were 2.27 hr, 0.56 L h kg , 1.66 L/kg and 8.91 hr*µg/ml, respectively. While diclofenac and flunixin meglumine significantly increased the t and AUC of moxifloxacin, they significantly reduced the Cl and V . These results suggest that anti-inflammatory drugs could increase the therapeutic efficacy of moxifloxacin by altering its pharmacokinetics.
在本研究中,测定了莫西沙星(5毫克/千克)在绵羊体内单次静脉注射后的药代动力学,分别是单独注射莫西沙星以及与双氯芬酸(2.5毫克/千克)或氟尼辛葡甲胺(2.2毫克/千克)联合给药后的药代动力学。使用了6只健康的阿克卡拉曼绵羊(年龄2±0.3岁,体重53.5±5千克)。在三个阶段采用了具有15天洗脱期的纵向设计。在第一阶段,通过静脉注射给予莫西沙星。在第二和第三阶段,莫西沙星分别与静脉注射的双氯芬酸和氟尼辛葡甲胺联合给药。通过高效液相色谱法测定莫西沙星的血浆浓度。使用二室开放药代动力学模型计算药代动力学参数。单独静脉注射莫西沙星后,莫西沙星的平均消除半衰期(t)、总体清除率(Cl)、稳态分布容积(V)和曲线下面积(AUC)分别为2.27小时、0.56升/小时·千克、1.66升/千克和8.91小时·微克/毫升。虽然双氯芬酸和氟尼辛葡甲胺显著增加了莫西沙星的t和AUC,但它们显著降低了Cl和V。这些结果表明,抗炎药物可通过改变莫西沙星的药代动力学来提高其治疗效果。