Michanek Peter, Bröjer Johan, Lilliehöök Inger, Fjordbakk Cathrine T, Löwgren Minerva, Hedeland Mikael, Bergquist Jonas, Ekstrand Carl
Department of Animal Biosciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
J Vet Pharmacol Ther. 2025 Jan;48 Suppl 1(Suppl 1):41-49. doi: 10.1111/jvp.13476. Epub 2024 Aug 7.
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 T of 7 h, a C of 2350 ng/mL, and a t of 28.5 h. CFZ treatment reduced glucose (AUC, p = 0.001) and insulin (AUC, 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.
卡格列净（CFZ）是一种钠-葡萄糖协同转运蛋白2抑制剂，已显示出作为治疗马匹胰岛素调节异常药物的良好效果。尽管CFZ已在临床上使用，但此前尚未发表过药代动力学数据。在本研究中，检测了8匹健康冰岛马单次口服1.8 mg/kg剂量后CFZ的药代动力学。此外，还研究了治疗对分级葡萄糖输注后血糖和胰岛素水平的影响。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定量的血浆样本。使用超高效液相色谱-串联四极杆质谱联用仪（UHPLC-MS/MS）对CFZ进行定量。非房室分析揭示了关键的药代动力学参数，包括中位达峰时间为7小时、峰浓度为2350 ng/mL、消除半衰期为28.5小时。CFZ治疗降低了治疗后5小时给予的分级葡萄糖输注后的血糖（曲线下面积，p = 0.001）和胰岛素（曲线下面积，p = 0.04）反应。这表明在健康冰岛马中单次给药后起效迅速。未观察到与治疗相关的明显不良反应。
