Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Bukgu, Daegu, South Korea.
PLoS One. 2020 Jun 4;15(6):e0234211. doi: 10.1371/journal.pone.0234211. eCollection 2020.
Fluoroquinolone resistance in Salmonella Typhimurium is becoming a major concern. Hence, an intervention to limit the growth in resistance is inevitable. One way to combat this challenge is through combination therapy. The combination of antibiotics with phytochemicals has become an ideal means of preventing antimicrobial resistance. Recently, in an in vitro study, the combination of methyl gallate (MG) with marbofloxacin (MAR) has shown to prevent Salmonella Typhimurium invasion. It is also worth to study the effects of plant extracts on the pharmacokinetics of antibiotics. Hence, the objective of this study was to determine the effect of MG on the pharmacokinetics of MAR and pharmacokinetics/pharmacodynamics integration of MG and MAR. The micro-broth dilution method was used to obtain the minimum inhibitory concentration (MIC), and fractional inhibitory concentration (FIC) of MAR and MG. Whereas, the pharmacokinetic was conducted in rats by administering either MAR alone or combined with MG through oral and/or intravenous routes. The results indicated that the MIC of MAR and MG against standard strain Salmonella Typhimurium (ATCC 14028) was 0.031 and 500 μg/mL, respectively. The FICindex of the combination of MAR and MG was 0.5. For orally administered drugs, the Cmax and AUC24h of MAR were 1.04 and 0.78 μg/mL and 5.98 and 6.11 h.μg/mL when MAR was given alone and in combination with MG, respectively. The intravenous administration of MAR showed a half-life of 3.8 and 3.9 h; a clearance rate of 1.1 and 0.73 L/h/kg and a volume of distribution of 5.98 and 4.13 L/kg for MAR alone and in combination with MG, respectively. The AUC24/MIC for MAR alone and in combination with MG was 192.8 and 381.9 h, respectively. In conclusion, MG has shown to increase the antimicrobial activity of MAR in vitro and ex vivo experiments without affecting the pharmacokinetics of MAR in rats.
氟喹诺酮类药物耐药性在鼠伤寒沙门氏菌中日益受到关注。因此，采取干预措施限制耐药性的增长是不可避免的。一种对抗这一挑战的方法是联合治疗。抗生素与植物化学物质的联合已成为预防抗菌药物耐药性的理想手段。最近，在一项体外研究中，发现没食子酸甲酯（MG）与马波沙星（MAR）联合使用可防止鼠伤寒沙门氏菌的入侵。研究植物提取物对抗生素药代动力学的影响也很有价值。因此，本研究的目的是确定 MG 对 MAR 药代动力学的影响，以及 MG 和 MAR 的药代动力学/药效学整合。采用微量肉汤稀释法测定 MAR 和 MG 的最低抑菌浓度（MIC）和部分抑菌浓度（FIC）。而在大鼠中进行药代动力学研究，通过口服和/或静脉途径单独给予 MAR 或与 MG 联合给予 MAR。结果表明，MAR 和 MG 对标准鼠伤寒沙门氏菌（ATCC 14028）的 MIC 分别为 0.031 和 500μg/mL，MAR 和 MG 联合使用的 FICindex 为 0.5。对于口服药物，MAR 单独和与 MG 联合使用时，Cmax 和 AUC24h 分别为 1.04 和 0.78μg/mL 和 5.98 和 6.11 h.μg/mL。MAR 静脉注射的半衰期为 3.8 和 3.9 h，清除率分别为 1.1 和 0.73 L/h/kg，分布容积分别为 5.98 和 4.13 L/kg。MAR 单独和与 MG 联合使用时的 AUC24/MIC 分别为 192.8 和 381.9 h。结论：MG 显示在体外和体内实验中增加了 MAR 的抗菌活性，而不影响 MAR 在大鼠体内的药代动力学。
