当前位置: X-MOL 学术Microb. Pathog. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
The dose regimen formulation of tilmicosin against Lawsonia intracellularis in pigs by pharmacokinetic-pharmacodynamic (PK-PD) model.
Microbial Pathogenesis ( IF 3.3 ) Pub Date : 2020-07-21 , DOI: 10.1016/j.micpath.2020.104389
Wanhe Luo 1 , Hua Qin 2 , Dongmei Chen 3 , Mengru Wu 1 , Kuiyu Meng 1 , Aoxue Zhang 1 , Yunahu Pan 1 , Wei Qu 1 , Shuyu Xie 1
Affiliation  

In this study, the rational dose regimens of tilmicosin against Lawsonia intracellularis (L. intracellularis) were studied using pharmacokinetic-pharmacodynamic (PK-PD) model approach to provide a maximal efficacy. The healthy and infected pigs were orally administrated the tilmicosin premix at a single dose of 10 mg/kg, and then the plasma and ileum content were collected at different time points. The time to peak (Tmax), the peak concentration (Cmax), the area under concentration time curve (AUC0–24h), the apparent volume of distribution by bioavailability (V/F), the body clearance rate by bioavailability (CL/F) and the mean residence time (MRT) of tilmicosin premix for plasma were 2.00 h, 1.08 ± 0.04 μg/mL, 9.61 ± 1.47 μg h/mL, 34.43 ± 1.02 L/kg, 0.71 ± 0.03 L/h/kg and 15.03 ± 0.04 h in healthy pigs, and 2.00 h, 0.99 ± 0.03 μg/mL, 9.30 ± 1.43 μg h/mL, 58.59 ± 1.81 L/kg, 0.44 ± 0.02 L/h/kg and 15.75 ± 0.03 h in infected pigs, respectively. The Tmax, Cmax, AUC0–24h, V/F, CL/F and MRT of tilmicosin premix for ileum content were 2.00 h, 3.78 ± 0.03 μg/mL, 20.41 ± 1.64 μg h/mL, 11.29 ± 0.97 L/kg, 0.44 ± 0.02 L/h/kg and 11.29 ± 0.09 h in healthy pigs, and 2.00 h, 3.41 ± 0.06 μg/mL, 22.65 ± 1.32 μg h/mL, 8.16 ± 1.51 L/kg, 0.41 ± 0.01 L/h/kg and 11.44 ± 0.05 h in infected pigs, respectively. Based on the intracellular minimum inhibitory concentration (MIC) of L. intracellularis isolate was 2 μg/mL, the results of the mutant prevention concentration (MPC), the post-antibiotic effect (PAE) and time-killing curves all showed strong concentration-dependenttendencies. Integrating the in vivo pharmacokinetic data of infected pigs and ex vivo pharmacodynamic data using the sigmoid Emax (Hill) equation to obtain the ileum content AUC0–24h/MIC values of 6.87, 26.80, and 36.02 h to achieve the bacteriostatic activity, bactericidal activity, and virtual eradication of bacteria, respectively. Based on these results, a dosage regimen of daily 14.39 mg/kg for 3 d could be sufficient in the treatment of L. intracellularis. This study will provide a guidance of dosage regimen formulation for drug against animal intracellular bacterial infections.



中文翻译:

通过药代动力学-药效学(PK-PD)模型,对猪中的替莫米星针对猪胞内劳森菌的剂量方案进行配制。

在这项研究中,使用药代动力学-药效学(PK-PD)模型方法研究了替米克星对胞内劳森菌L. intracellularis)的合理剂量方案,以提供最大的疗效。健康和感染的猪以10 mg / kg的单剂量口服替米考星预混物,然后在不同时间点收集血浆和回肠含量。达到峰值的时间(T max),峰值浓度(C max),浓度时间曲线下的面积(AUC 0-24h),替米考星预混物在血浆中的生物利用度(V / F)分布的表观分布量,生物利用度(CL / F)的清除率和平均停留时间(MRT)为2.00 h,1.08±0.04μg/ mL,健康猪为9.61±1.47μgh / mL,34.43±1.02 L / kg,0.71±0.03 L / h / kg和15.03±0.04 h,2.00 h,0.99±0.03μg/ mL,9.30±1.43μgh / mL在感染猪中分别为58.59±1.81 L / kg,0.44±0.02 L / h / kg和15.75±0.03 h。T max,C max,AUC 0-24h,回肠含量的替米考星预混物的V / F,CL / F和MRT为2.00 h,3.78±0.03μg/ mL,20.41±1.64μgh / mL,11.29±0.97 L / kg,0.44±0.02 L / h / kg和健康猪为11.29±0.09 h,感染猪为2.00 h,3.41±0.06μg/ mL,22.65±1.32μgh / mL,8.16±1.51 L / kg,0.41±0.01 L / h / kg和11.44±0.05 h , 分别。根据细胞内劳森氏菌分离物的细胞内最低抑菌浓度(MIC)为2μg/ mL,突变预防浓度(MPC),抗生素后效果(PAE)和时间杀灭曲线的结果均显示强浓度-相依倾向。整合体内感染猪和药代动力学数据体外使用乙状结肠Ë药效学数据最大值(Hill)方程获得回肠含量AUC 0-24h / MIC值分别为6.87、26.80和36.02 h,以实现抑菌活性,杀菌活性和虚拟消灭细菌。根据这些结果,每日剂量14.39 mg / kg连续3 d足以治疗胞内劳森氏菌。这项研究将提供针对动物细胞内细菌感染的药物剂量方案的指导。

更新日期:2020-07-21
down
wechat
bug