The aim of this study was to determine the pharmacokinetic parameters of doxycycline in dogs and assess the efficacy of an oral drug dosage regimen of 10 mg/kg daily for 28 days through Pharmacokinetic/Pharmacodynamic (PK/PD) target analysis based on Monte Carlo simulation, using previously published data for the zoonotic pathogen Staphylococcus pseudintermedius. After a multiple-dosage regimen, the accumulation index was 1.88 ± 0.82. The Cmax_ss and Cmin_ss values were 5.18 ± 1.81 µg/ml and 1.91 ± 1.35 µg/ml, respectively. There were statistically significant differences for Cmax, Cmin at 24 hr, MRTt, AUCt and AUC∞ between days 1 and 28. The Cmin_ss value was over the MIC of the principal pathogens, and Cmax_ss was higher than the resistance values (>2 μg/ml). For AUC/MIC indices of 12, 25 and 40, the cumulative fraction responses (CFR) were 94.01%, 69.55% and 60.86%, respectively; for an MIC value of 2 µg/ml, the corresponding probability of target attainment (PTA) was 99.94%, 84.78% and 45.16%, respectively. Doxycycline was used against numerous localized infections in different organs and tissues. For the strains with MIC < 1 μg/mL, PTA was close to 100%, even for the most demanding ones, specifically 94.98% for an index of 40% and 99.9% for an index of 25.

中文翻译：

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犬多西环素口服给药后的药代动力学

本研究的目的是确定多西环素在犬体内的药代动力学参数，并通过基于蒙特卡罗模拟的药代动力学/药效学 (PK/PD) 目标分析，评估每天 10 mg/kg 口服药物剂量方案 28 天的疗效。 ，使用先前公布的人畜共患病病原体金黄色葡萄球菌的数据。多次给药后，蓄积指数为 1.88 ± 0.82。Cmax _ss和 Cmin _ss值分别为 5.18 ± 1.81 µg/ml 和 1.91 ± 1.35 µg/ml。第 1 天和第 28 天之间的 Cmax、24 小时时的 Cmin、MRTt、AUCt 和 AUC∞ 存在统计学显着差异。 Cmin _ss值超过主要病原体的 MIC，Cmax _ss高于电阻值 (>2 μg/ml)。对于 12、25 和 40 的 AUC/MIC 指数，累积分数反应 (CFR) 分别为 94.01%、69.55% 和 60.86%；对于 2 µg/ml 的 MIC 值，相应的目标实现概率 (PTA) 分别为 99.94%、84.78% 和 45.16%。多西环素用于治疗不同器官和组织中的多种局部感染。对于 MIC < 1 μg/mL 的菌株，即使是最苛刻的菌株，PTA 也接近 100%，特别是指数为 40% 的菌株为 94.98%，指数为 25 的菌株为 99.9%。