Abstract：
Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor that has shown promising results as a drug for the treatment of insulin dysregulation in horses. Even though CFZ is used clinically, no pharmacokinetic data has previously been published. In this study, the pharmacokinetics of CFZ after administration of a single oral dose of 1.8 mg/kg in eight healthy Icelandic horses was examined. Additionally, the effect of treatment on glucose and insulin levels in response to a graded glucose infusion was investigated. Plasma samples for CFZ quantification were taken at 0, 0.33, 0.66, 1, 1.33, 1.66, 2, 2.33, 2.66, 3, 3.5, 4, 5, 6, 8, 12, 24, 32, and 48 h post administration. CFZ was quantified using UHPLC coupled to tandem quadrupole mass spectrometry (UHPLC-MS/MS). A non-compartmental analysis revealed key pharmacokinetic parameters, including a median Tmax of 7 h, a Cmax of 2350 ng/mL, and a t1/2Z of 28.5 h. CFZ treatment reduced glucose (AUCGLU, p = 0.001) and insulin (AUCINS, p = 0.04) response to a graded glucose infusion administered 5 h after treatment. This indicates a rapid onset of action following a single dose in healthy Icelandic horses. No obvious adverse effects related to the treatment were observed.
摘要：
Canagliflozin（CFZ）是一种钠-葡萄糖协同转运蛋白2抑制剂，已显示出有望作为治疗马胰岛素失调的药物的结果。即使CFZ在临床上使用，以前没有发表药代动力学数据.在这项研究中,研究了8匹健康的冰岛马匹单次口服剂量1.8mg/kg后CFZ的药代动力学。此外,研究了分级葡萄糖输注对葡萄糖和胰岛素水平的影响.在给药后0、0.33、0.66、1、1.33、1.66、2、2.33、2.66、3、3.5、4、5、6、8、12、24、32和48小时采集用于CFZ定量的血浆样品。使用与串联四极杆质谱联用的UHPLC(UHPLC-MS/MS)定量CFZ。非房室分析揭示了关键的药代动力学参数，包括7h的中值Tmax，aCmax为2350ng/mL，和28.5h的t1/2Z。CFZ处理降低了葡萄糖(AUCGLU，p=0.001）和胰岛素（AUCINS，p=0.04）对治疗后5小时给予的分级葡萄糖输注的反应。这表明在健康的冰岛马中单次剂量后迅速开始作用。未观察到与治疗相关的明显不良反应。
