In vivo Pharmacokinetic/Pharmacodynamic (PK/PD) Profiles of Tulathromycin in an Experimental Intraperitoneal Haemophilus parasuis Infection Model in Neutropenic Guinea Pigs.
In vivo Pharmacokinetic/Pharmacodynamic (PK/PD) Profiles of Tulathromycin in an Experimental Intraperitoneal Haemophilus parasuis Infection Model in Neutropenic Guinea Pigs.
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DOI：
10.3389/fvets.2021.715887
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发表时间：
2021
影响因子：
3.2
通讯作者：
Zhao YD
中科院分区：
文献类型：
--
作者：
Guo LL;Gao RY;Wang LH;Lin SJ;Fang BH;Zhao YD
泰拉霉素是一种半合成的大环内酯类抗菌剂，在兽医呼吸道疾病中具有重要作用。本研究的目的是建立一个药代动力学/药效学（PK/PD）模型，以检查有效性，并确定最佳剂量的妥拉霉素肌内（IM）治疗后，腹腔内接种后诱导的副猪嗜血杆菌感染的贫血豚鼠。在H.通过液相色谱-串联质谱法（LC-MS/MS）评价了副猪流感感染的豚鼠。泰拉霉素对H.豚鼠血清（0.03 μg/mL）中的猪副伤寒沙门氏菌浓度比阳离子调节的Mueller-Hinton肉汤（CAMHB）（0.5 μg/mL）低约16倍。168 h药时曲线下面积（AUC）与MIC的比值（AUC 168 h/MIC）与泰拉霉素的体内抗菌效果呈正相关（血清中R2 = 0.9878，肺组织中R2 = 0.9911）。根据AUC 72 h/MIC比值计算的达到2-log 10 CFU/肺降低的剂量为5.7 mg/kg（血清）和2.5 mg/kg（肺组织），低于AUC 168 h/MIC的血清和肺组织的13.2 mg/kg和8.9 mg/kg。此外，使用2-log 10降低作为目标，AUC 0 − 72 h作为PK/PD指数值可能更现实。本研究结果为PK/PD模型在大环内酯类抗生素治疗呼吸系统疾病研究中的应用奠定了基础。
Tulathromycin is a semi-synthetic macrolide antimicrobial that has an important role in veterinary medicine for respiratory disease. The objective of the study was to develop a pharmacokinetic/pharmacodynamic (PK/PD) model to examine the efficacy and determine an optimal dosage of tulathromycin intramuscular (IM) treatment against Haemophilus parasuis infection induced after intraperitoneal inoculation in neutropenic guinea pigs. The PKs of tulathromycin in serum and lung tissue after intramuscular administration at doses of 1, 10, and 20 mg/kg in H. parasuis-infected neutropenic guinea pigs were evaluated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The tulathromycin minimum inhibitory concentration (MIC) against H. parasuis was ~16 times lower in guinea pig serum (0.03 μg/mL) than in cation-adjusted Mueller-Hinton broth (CAMHB) (0.5 μg/mL). The ratio of the 168-h area under the concentration-time curve (AUC) to MIC (AUC168h/MIC) positively correlated with the in vivo antibacterial effectiveness of tulathromycin (R2 = 0.9878 in serum and R2 = 0.9911 in lung tissue). The computed doses to achieve a reduction of 2-log10 CFU/lung from the ratios of AUC72h/MIC were 5.7 mg/kg for serum and 2.5 mg/kg for lung tissue, which lower than the values of 13.2 mg/kg for serum and 8.9 mg/kg for lung tissue with AUC168h/MIC. In addition, using as objective a 2-log10 reduction and an AUC0−72h as the value of the PK/PD index could be more realistic. The results of this study could provide a solid foundation for the application of PK/PD models in research on macrolide antibiotics used to treat respiratory diseases.
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影响因子：
3.7
作者：
Brockmeier SL;Register KB;Kuehn JS;Nicholson TL;Loving CL;Bayles DO;Shore SM;Phillips GJ
通讯作者：
Phillips GJ
影响因子：
3.3
作者：
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影响因子：
2.4
作者：
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
4.4
作者：
Kavanová L;Matiašková K;Levá L;Štěpánová H;Nedbalcová K;Matiašovic J;Faldyna M;Salát J
通讯作者：
Salát J