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

ABSTRACT: 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 ?g/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 ?g/mL and 5.98 and 6.11 h.?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 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.

SUBMITTER: Birhanu BT

PROVIDER: S-EPMC7272065 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Birhanu Biruk Tesfaye BT Lee Eon-Bee EB Park Seung-Chun SC

PloS one 20200604 6

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 wor ...[more]

PMID: 32497083

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Project description:Salmonella typhimurium is a highly transmissible pathogen in rabbits that causes significant losses. Danofloxacin shows excellent efficacy against S. typhimurium infections. However, there are few reports of the pharmacokinetic/pharmacodynamic (PK/PD) modeling of danofloxacin against this pathogen. The aim of this study was to evaluate the in vivo PK/PD relationship of danofloxacin in rabbits infected with S. typhimurium. We used the reduction of bacterial burden in the blood, liver, spleen, and lung as the target PD endpoints, and determined the PK/PD indexes that best correlated with the efficacy and its corresponding magnitude. Danofloxacin was administrated orally to experimentally S. typhimurium-infected rabbits once daily for three successive days. The concentrations of danofloxacin in the serum and the bacterial burden in the blood, liver, spleen, and lung were determined. The PK/PD relationships of danofloxacin against S. typhimurium were evaluated using a Sigmoid Emax model. The results showed that the area under the concentration-time curve from 0 to 24 h/minimum inhibitory concentration (AUC24 h/MIC) ratio correlated well with the in vivo antibacterial effectiveness in different organs, with an r2 of 0.8971, 0.9186, 0.9581, and 0.8708 in the blood, liver, spleen, and lung, respectively. The AUC24 h/MIC ratios for the bactericidal effect (3 × Log10 colony forming units/mL reductions) were 121.30, 354.28, 216.64, and 228.66 in the blood, liver, spleen, and lung, respectively, indicating that the in vivo effectiveness of danofloxacin against S. typhimurium using bacterial reduction in different organs as PD endpoints was not identical. This study illustrated that the selection of the target organ for bacterial reduction determination had little effect on best PK/PD parameter determination, but is critical for parameter magnitude calculation in antimicrobial PK/PD modeling, and furthermore, has an impact on the rational dosage optimization process.

Dataset Information

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

Publications

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

Similar Datasets

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