Evaluation of the pharmacokinetic-pharmacodynamic integration of marbofloxacin in combination with methyl gallate against Salmonella Typhimurium in rats

• Published in: PloS one Vol. 15; no. 6; p. e0234211
• Main Authors: Birhanu, Biruk Tesfaye, Lee, Eon-Bee, Park, Seung-Chun
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 04.06.2020; Public Library of Science (PLoS)
• Subjects: Animal experimentation; Antibacterial agents; Antibiotics; Antimicrobial activity; Antimicrobial agents; Antimicrobial resistance; Biological products; Biology and Life Sciences; Chromatography; Dilution; Drug dosages; Drug resistance; EDTA; Evaluation; Fluoroquinolones; Health aspects; Integration; Intravenous administration; Laboratory animals; Medicine and Health Sciences; Methicillin; Methyl compounds; Microbial drug resistance; Minimum inhibitory concentration; Oral administration; Pharmacodynamics; Pharmacokinetics; Pharmacology; Plant extracts; Plasma; Salmonella; Salmonella food poisoning; Salmonella Typhimurium; Staphylococcus infections; Testing; Veterinary colleges; Veterinary medicine; India; United States > US; South Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0234211

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 [mu]g/mL, respectively. The FIC.sub.index of the combination of MAR and MG was 0.5. For orally administered drugs, the C.sub.max and AUC.sub.24h of MAR were 1.04 and 0.78 [mu]g/mL and 5.98 and 6.11 h.[mu]g/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 AUC.sub.24 /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.