Exploring montelukast in dogs: A preliminary pharmacokinetic study following oral administration under fasted and fed conditions

IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES Veterinary journal Pub Date : 2024-08-05 DOI:10.1016/j.tvjl.2024.106210
Charbel Fadel , Beata Łebkowska-Wieruszewska , Andrzej Lisowski , Firas Serih , Amnart Poapolathep , Mario Giorgi
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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 Blood was withdrawn to heparinized tubes at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 24 hr.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.

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探索狗体内的孟鲁司特:在禁食和进食条件下口服后的初步药代动力学研究。
本研究调查了蒙曲司特 (MTK) 的药代动力学 (PK),蒙曲司特是一种半胱氨酰白三烯受体拮抗剂,在兽医领域越来越受到重视。在狗身上,MTK 的适应症主要是治疗特应性皮炎,属于标签外用途。六只雄性拉布拉多犬分别在禁食和进食条件下口服一次MTK(40毫克/只),采用开放式、单剂量、两疗程、两阶段、交叉设计,冲洗期为一周。分别在 0、0.25、0.5、0.75、1、1.5、2、4、6、8、10 和 24 小时抽血至肝素化试管。采用经过验证的高效液相色谱法对 MTK 血浆浓度进行定量,并使用 PKanalixTM 软件对数据进行非室分析。在两种条件下,给药后 24 小时的浓度仍可定量。空腹和进食状态下的 PK 参数无明显差异。MTK 的消除速度相对较慢,空腹和进食后的 t1/2 值分别为 8.10 小时和 7.68 小时。达到最大浓度(Cmax)的Tmax为4小时,空腹和进食状态下的平均值分别为1.98μg/mL和2.80μg/mL。鉴于MTK在狗体内的治疗范围尚不明确,也没有对照研究证明其在狗体内的疗效,因此应根据当前的PK数据和确定有效治疗范围(如果存在)的需要,考虑进一步调整和完善剂量。未来的研究应侧重于疗效研究、多剂量调查和药效学评估,以评估 MTK 是否适合在狗体内使用。
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来源期刊
Veterinary journal
Veterinary journal 农林科学-兽医学
CiteScore
4.10
自引率
4.50%
发文量
79
审稿时长
40 days
期刊介绍: The Veterinary Journal (established 1875) publishes worldwide contributions on all aspects of veterinary science and its related subjects. It provides regular book reviews and a short communications section. The journal regularly commissions topical reviews and commentaries on features of major importance. Research areas include infectious diseases, applied biochemistry, parasitology, endocrinology, microbiology, immunology, pathology, pharmacology, physiology, molecular biology, immunogenetics, surgery, ophthalmology, dermatology and oncology.
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