Moxifloxacin-Loaded Nanoemulsions Having Tocopheryl Succinate as the Integral Component Improves Pharmacokinetics and Enhances Survival in<i>E. coli</i>-Induced Complicated Intra-Abdominal Infection

Shukla, P.K.; Verma, Ajeet Kumar; Dwivedi, Pankaj; Yadav, Arti; Gupta, Pramod; Rath, Srikanta Kumar; Mishra, Prabhat Ranjan

doi:10.1021/mp5003762

Cited by 10 publications

(1 citation statement)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moxifloxacin (MXF) is a fluoroquinolone that is effective against Gram-positive and Gram-negative bacteria ( 22 ). Its bidirectional effects on the activation and inhibition of the immune response were demonstrated by its effects on the production of a number of cytokines (including TNF-α and IL6) in human and murine leukocytes ( 23 ). Similar immunomodulatory effects of fluoroquinolones in inflammatory states and infection have additionally been demonstrated in various previous in vitro studies; for example, clinically relevant concentrations of MXF were demonstrated to inhibit the synthesis of inflammatory mediators, including IL-1, TNF-α, IL-6 and IL-8, in human peripheral blood mononuclear cells and endothelial cells following LPS stimulation ( 24 ).…”

Section: Introductionmentioning

confidence: 99%

Bidirectional effects of moxifloxacin on the pro‑inflammatory response in lipopolysaccharide‑stimulated mouse peritoneal macrophages

Qiu

Yuan

et al. 2018

Mol Med Report

View full text Add to dashboard Cite

Sepsis is a systemic inflammatory condition in response to life-threatening infections, and macrophages are a key source of inflammatory cytokines. Moxifloxacin (MXF) has antibacterial activity in Gram-positive and Gram-negative bacteria. The present study investigated the effects of MXF on a lipopolysaccharide (LPS)-stimulated inflammatory response and gene expression in macrophages. Peritoneal macrophages were isolated from male C57BL/6J mice and treated with LPS and/or MXF. The mRNA and protein expression of toll-like receptor 4 (TLR4), sphingosine kinase 1 (SPHK1) and nuclear factor (NF)-κB was determined by quantitative polymerase chain reaction, western blotting and immunofluorescence analysis. The expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 was determined with ELISAs. The data demonstrated that MXF dose-dependently decreased the viability of macrophages, and 8 and 16 µg/ml MXF prevented the LPS-induced increase in TLR4, SPHK1, NF-κB p65, TNF-α and IL-6 expression. The inhibition was most effective at a concentration of 16 µg/ml MXF, whereas, 64 µg/ml MXF exerted a pro-inflammatory effect. Collectively, the data demonstrated a bidirectional effect of MXF: Lower MXF concentrations (8 and 16 µg/ml) inhibited the inflammatory response; however, a higher MXF concentration (64 µg/ml) had a pro-inflammatory effect on LPS-treated mouse peritoneal macrophages. In conclusion, these results suggested the importance of MXF as an inhibitor of the inflammatory response at an optimal dose. MXF inhibition of the inflammatory response may be mediated by TLR4 signaling.

show abstract

Section: Introductionmentioning

confidence: 99%

Bidirectional effects of moxifloxacin on the pro‑inflammatory response in lipopolysaccharide‑stimulated mouse peritoneal macrophages

Qiu

Yuan

et al. 2018

Mol Med Report

View full text Add to dashboard Cite

show abstract

Drug–drug interactions between moxifloxacin and rifampicin based on pharmacokinetics in vivo in rats

Huang

Liu

et al. 2016

Biomedical Chromatography

View full text Add to dashboard Cite

Moxifloxacin and rifampicin are all the first-line options for the treatment of active tuberculosis, which are often combined for the treatment of multidrug resistance pulmonary tuberculosis in clinic. However, the potential drug-drug interactions between moxifloxacin and rifampicin were unknown. The aim of this study was to investigate the drug-drug interactions between moxifloxacin and rifampicin based on their pharmacokinetics in vivo after oral administration of the single drug and both drugs, and reveal their mutual effects on their pharmacokinetics. Eighteen male Sprague-Dawley rats were randomly assigned to three groups: moxifloxacin group, rifampicin group and moxifloxacin + rifampicin group. Plasma concentrations of moxifloxacin and rifampicin were determined using LC-MS at the designated time points after drug administration, and the main pharmacokinetic parameters were calculated. In addition, effects of moxifloxacin and rifampicin on their metabolic rate and absorption were investigated using rat liver microsome incubation systems and Caco-2 cell transwell model. The main pharmacokinetic parameters of moxifloxacin including Tmax , Cmax , t1/2 and AUC(0-t) increased more in the moxifloxacin + rifampicin group than in the moxifloxacin group, but the difference was not significant (p > 0.05). However, the pharmacokinetic parameters of rifampicin, including peak concentration, area under the concentration-time curve, half-life and the area under the first moment plasma concentration-time curve, increased significantly (p < 0.05) compared with the rifampicin group, and the time to peak concentration decreased significantly (p < 0.05). The mean residence time of rifampicin also increased in moxifloxacin + rifampicin group compared with the rifampicin group, but the difference was not significant (p > 0.05). The rat liver microsome incubation experiment indicated that moxifloxacin could increase the metabolic rate of rifampicin from 23.7 to 38.7 min. However, the Caco-2 cell transwell experiment showed that moxifloxacin could not affect the absorption rate of rifampicin. These changes could enhance the drug efficacy, but they could also cause drug accumulation, which might induce adverse effect, so it was suggested that the drug dosage should be adjusted and the drug concentration in plasma should be monitored if moxifloxacin and rifampicin are co-administered. Copyright © 2016 John Wiley & Sons, Ltd.

show abstract

Probiotic Properties of Alcaligenes faecalis Isolated from Argyrosomus regius in Experimental Peritonitis (Rat Model)

Gutiérrez-Falcón

Ramos-Nuez

Zayas

et al. 2021

Probiotics & Antimicro. Prot.

View full text Add to dashboard Cite

A strain of Alcaligenes faecalis A12C (A. faecalis A12C) isolated from Argyrosomus regius is a probiotic in fish. Previous experiments showed that A. faecalis A12C had inhibitory effects on the growth of multidrug-resistant bacteria. We aimed to confirm whether A. faecalis A12C is safe and has adequate intestinal colonization in experimental rats, and evaluate its efficacy in an animal model of peritonitis. We used 30 male rats, randomly divided into 6 groups (n = 5): three groups (HA7, HA15, HA30) received A. faecalis A12C in drinking water (6 × 108 CFU/mL) for 7 days, and three control groups received drinking water only. All groups were evaluated at 7, 15, and 30 days. Survival after A. faecalis A12C administration was 100% in all groups. Mild eosinophilia (1.5%, p < 0.01) and increased aspartate aminotransferase (86 IU/L, p < 0.05) were observed in HA7, followed by progressive normalization. No histological signs of organ injury were found. We observed significant E. coli decline in faeces, parallel to an increase in A. faecalis A12C at 7 days. E. coli had a tendency to recover initial values, while A. faecalis A12C disappeared from the intestinal microbiota at 30 days. To evaluate its efficacy against peritonitis, we studied two additional groups of animals: IA group pretreated with A. faecalis A12C before E. coli intra-abdominal inoculation, and IC group inoculated with no A. faecalis A12C. We found an increase in C-reactive protein, alanine aminotransferase, urea, and eosinophils in IC animals when compared with IA. Peritonitis was more evident in IC than in IA animals. Our findings suggest that A. faecalis A12C altered clinically relevant parameters in sepsis and was associated with a lesser spread of infection.

show abstract

Moxifloxacin-Loaded Nanoemulsions Having Tocopheryl Succinate as the Integral Component Improves Pharmacokinetics and Enhances Survival inE. coli-Induced Complicated Intra-Abdominal Infection

Cited by 10 publications

References 74 publications

Bidirectional effects of moxifloxacin on the pro‑inflammatory response in lipopolysaccharide‑stimulated mouse peritoneal macrophages

Bidirectional effects of moxifloxacin on the pro‑inflammatory response in lipopolysaccharide‑stimulated mouse peritoneal macrophages

Drug–drug interactions between moxifloxacin and rifampicin based on pharmacokinetics in vivo in rats

Probiotic Properties of Alcaligenes faecalis Isolated from Argyrosomus regius in Experimental Peritonitis (Rat Model)

Contact Info

Product

Resources

About