The pharmacokinetics/pharmacodynamics integration of tilmicosin against Mycoplasma synoviae in vitro and in vivo

IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Journal of veterinary pharmacology and therapeutics Pub Date : 2024-08-12 DOI:10.1111/jvp.13475
Xiu Yan, Jinxin Liu, Weihuo Li, Shuti Song, Zhaofeng Yao, Yixin Jia, Sheng Yuan, Hong Yang, Nan Zhang
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Abstract

Mycoplasma synoviae (MS) infection is a serious threat to poultry industry in China. Tilmicosin is a semisynthetic macrolide antibiotic used only in animals and has shown potential efficacy against MS, but there were no reported articles concerning the pharmacokinetics/pharmacodynamics (PK/PD) interactions of tilmicosin against MS in vitro and vivo. This study aimed to assess the antibacterial activity of tilmicosin against MS in vitro and in vivo using PK/PD model to provide maximal efficacy. The minimum inhibitory concentration (MIC) and killing rates of different drug concentrations were measured using the microdilution method in vitro. Then, tilmicosin was administered orally to the MS-infected chickens at doses of 7.5 and 60 mg/kg, and the PK parameters of tilmicosin in joint dialysates were determined using high-pressure liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) combined with the microdialysis technique. The antibacterial effect (△E) was calculated when the infected chickens were administered a single oral dose of tilmicosin at 4, 7.5, 15, 30, and 60 mg/kg b.w. The PK and PD data were fitted using the Sigmoid Emax model to evaluate the PK/PD interactions of tilmicosin against MS. The bactericidal activity of tilmicosin against MS was concentration dependent. Furthermore, the PK/PD index of AUC0–72h/MIC exhibited the most optimal fitting results (R2 = .98). The MS load decreased by 1, 2, and 3 Log10 CFU/mL, then AUC/MIC was determined as 13.99, 20.53, and 28.23 h, respectively, and the bactericidal effect can be achieved when the dose of MS-infected chickens is at 31.64 mg/kg b.w. The findings of this study hold significant implications for optimizing the treatment regimen for MS infection.

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替米考星对滑膜支原体的体外和体内药代动力学/药效学整合。
滑膜支原体(MS)感染严重威胁着中国的家禽业。替米考星是一种仅用于动物的半合成大环内酯类抗生素,对滑膜支原体感染有潜在疗效,但目前尚无关于替米考星在体外和体内对滑膜支原体感染的药代动力学/药效动力学(PK/PD)相互作用的报道。本研究旨在利用PK/PD模型评估替米考星在体外和体内对多发性硬化症的抗菌活性,以获得最大疗效。采用微量稀释法在体外测定了不同药物浓度的最低抑菌浓度(MIC)和杀灭率。采用高压液相色谱/串联质谱(HPLC-MS/MS)结合微透析技术测定了关节透析液中替米考星的PK参数。利用 Sigmoid Emax 模型对替米考星的 PK 和 PD 数据进行拟合,以评估替米考星对 MS 的 PK/PD 相互作用。替米考星对多发性硬化症的杀菌活性与浓度有关。此外,AUC0-72h/MIC的PK/PD指数显示出最理想的拟合结果(R2 = .98)。MS载量减少1、2和3 Log10 CFU/mL时,AUC/MIC分别为13.99、20.53和28.23 h,MS感染鸡的剂量为31.64 mg/kg体重时可达到杀菌效果。
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来源期刊
CiteScore
3.10
自引率
15.40%
发文量
69
审稿时长
8-16 weeks
期刊介绍: The Journal of Veterinary Pharmacology and Therapeutics (JVPT) is an international journal devoted to the publication of scientific papers in the basic and clinical aspects of veterinary pharmacology and toxicology, whether the study is in vitro, in vivo, ex vivo or in silico. The Journal is a forum for recent scientific information and developments in the discipline of veterinary pharmacology, including toxicology and therapeutics. Studies that are entirely in vitro will not be considered within the scope of JVPT unless the study has direct relevance to the use of the drug (including toxicants and feed additives) in veterinary species, or that it can be clearly demonstrated that a similar outcome would be expected in vivo. These studies should consider approved or widely used veterinary drugs and/or drugs with broad applicability to veterinary species.
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