Pharmacokinetic/pharmacodynamic profiles of baicalin against Mycoplasma gallisepticum in an in vivo infection model

黄芩苷在体内感染模型中对抗鸡毒支原体的药代动力学/药效学特征

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Abstract

Mycoplasma gallisepticum (M. gallisepticum), a devastating avian pathogen that commonly causes chronic respiratory disease in chicken, is responsible for tremendous economic losses to the poultry industry. Baicalin is the main constituent of Scutellaria baicalensis that shows potential therapeutic effects against M. gallisepticum. However, the pharmacokinetic/pharmacodynamics (PK/PD) profiles of baicalin against M. gallisepticum are not well understood. The main objective of the present study was to determine the relationship between the PK/PD index and efficacy of baicalin in the M. gallisepticum infection model in chickens. The experiments were carried out on 10-day-old chickens that were challenged with M. gallisepticum in the bilateral air sacs. While, baicalin was orally administrated once in a day for 3 consecutive days, started from d 3 postinfection. Ultra-performance liquid chromatography (UPLC) was used to evaluate the PK parameters of baicalin at doses of 200, 400, and 600 mg/kg in M. gallisepticum-infected chickens. Real-time PCR (RT-PCR) was used for the quantitative detection of M. gallisepticum in lungs. The PK and PD data were fitted to WinNonlin software to evaluate the PK/PD profiles of baicalin against M. gallisepticum. The minimum inhibitory concentration (MIC) of baicalin against M. gallisepticum strain R(low) was 31.25 µg/mL. The in vivo data suggested that baicalin concentration in the lung tissues was higher than plasma (1.21-1.73 times higher). The ratios of AUC(24h)/MIC of baicalin against bacteriostatic, bactericidal, and eradication were 0.62, 1.33, and 1.49 h, respectively. In conclusion, these results provided potential reference for future clinical dose selection of baicalin and evaluation of susceptibility breakpoints.

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