Abstract：
This study investigates the pharmacokinetics (PK) of montelukast (MTK), a cysteinyl leukotriene receptor antagonist increasingly being considered in veterinary medicine. In dogs, MTK has found indications mainly for treating atopic dermatitis as an off-label use. Six male Labrador dogs underwent a single oral administration of MTK (40 mg/dog) in both fasted and fed conditions according to an open, single-dose, two-treatment, two-phase, cross-over design, with a washout period of one week. Blood was withdrawn to heparinized tubes at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 24 hr. MTK plasma concentrations were quantified using a validated HPLC method, and the data were analysed using PKanalix™ software with a non-compartmental approach. Concentrations remained quantifiable at 24 hr after administration, under both conditions. No significant differences were observed in the PK parameters between the fasted and fed states. MTK was relatively eliminated slowly, with t1/2 values of 8.10 and 7.68 hr after fasted and fed states, respectively. The attainment of maximum concentration (Cmax) occurred at a Tmax of 4 hr, with mean values of 1.98 μg/mL and 2.80 μg/mL under fasted and fed conditions, respectively. Given the unknown therapeutic range of MTK in dogs and the absence of controlled studies proving its efficacy in this species, further dosing adjustments and refinements should be considered based on both the current PK data and the need to establish an effective therapeutic range, if present. Future research should focus on efficacy studies, multiple-dose investigations, and pharmacodynamic assessments to evaluate the suitability of MTK use in dogs.
摘要：
本研究调查了孟鲁司特（MTK）的药代动力学（PK），半胱氨酰白三烯受体拮抗剂在兽医学中越来越被考虑。在狗中，MTK已发现适应症主要用于治疗特应性皮炎作为非标签使用。六只雄性拉布拉多犬在禁食和进食条件下进行一次口服MTK（40mg/犬），单剂量,两种治疗，两相，交叉设计，冲洗期为一周。在0、0.25、0.5、0.75、1、1.5、2、4、6、8、10和24小时将血液抽取到肝素化的管中。使用经过验证的HPLC方法对MTK血浆浓度进行定量，并使用PKanalixTM软件与非房室方法分析数据。浓度在给药后24小时保持可量化，在这两种条件下。在禁食状态和进食状态之间的PK参数没有观察到显著差异。MTK的淘汰相对较慢，禁食和进食状态后的t1/2值为8.10和7.68hr，分别。达到最大浓度（Cmax）发生在4小时的Tmax，在禁食和进食条件下的平均值分别为1.98μg/mL和2.80μg/mL，分别。鉴于MTK在狗中的治疗范围未知，并且缺乏对照研究证明其在该物种中的功效，应根据当前的PK数据和建立有效治疗范围的需要考虑进一步的剂量调整和改进。如果存在。未来的研究应该集中在疗效研究上，多剂量调查,和药效学评估，以评估MTK在狗中使用的适用性。
