Pharmacokinetics and penetration of moxifloxacin into infected diabetic foot tissue in a large diabetic patient cohort

Majcher-Peszynska, Jolanta; Saß, Marko; Schipper, Sora; Czaika, V.; Gussmann, Andreas; Lobmann, Ralf; Mundkowski, Ralf G.; Luebbert, Christoph; Kujath, P.; Ruf, B.; Koch, Horst; Schareck, W.; Klar, E.; Drewelow, Bernd

doi:10.1007/s00228-010-0903-5

Cited by 14 publications

(12 citation statements)

References 18 publications

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“…Concentration values in perinecrotic wound tissue (in μg/g) in DFI have been reported previously to be fairly equivalent to concurrent plasma concentrations (in mg/L) . Our data basically confirm this result, and agree as well with data on the penetration of moxifloxacin into bone obtained during hip replacement surgery .…”

Section: Discussionsupporting

confidence: 92%

Population pharmacokinetics and target attainment analysis of moxifloxacin in patients with diabetic foot infections

Wicha¹,

Haak

Zink

et al. 2015

The Journal of Clinical Pharmacology

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The objective of this study was to provide a pharmacokinetic/pharmacodynamic (PK/PD) analysis of moxifloxacin in patients with diabetic foot infections (DFI). The plasma concentration-time courses were determined in 50 DFI patients on day 1 and 3 after intravenous moxifloxacin 400 mg once-daily. A two-compartment population pharmacokinetic model was developed, identifying as covariates total body weight on central and peripheral volume of distribution (V1, V2) and ideal body weight on clearance (CL), respectively. For a 70 kg patient V1 was 68.1 L (interindividual variability, CV: 27.4%), V2 44.6 L, and CL 12.1 L/h (25.6%). Simulations were performed to calculate the probability of target attainment (PTA) for Gram-positive and Gram-negative pathogens with fAUC/MIC targets of ≥30 and ≥100, respectively. PTA was 0.68-1 for susceptible (MIC ≤0.5 mg/L according to EUCAST) Gram-positive, but <0.25 for Gram-negative pathogens with MIC ≥0.25 mg/L. With the exception of the first 24 hours of therapy, obesity affected PTA only marginally. Pharmacokinetic parameters in DFI patients were similar to those reported for healthy volunteers, indicating the appropriateness of the standard dose of moxifloxacin. Overall clinical efficacy has been shown previously, but PTA is limited in a subpopulation infected with formally susceptible Gram-negative pathogens close to the EUCAST breakpoint.

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Section: Discussionsupporting

confidence: 92%

Population pharmacokinetics and target attainment analysis of moxifloxacin in patients with diabetic foot infections

Wicha¹,

Haak

Zink

et al. 2015

The Journal of Clinical Pharmacology

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“…Moxifloacin was expected to be useful as an anti-infective agent for respiratory tract, skin, soft tissues and intra-abdominal infections, including biliary tract and uterine infection [4,5,6,11,12,31], which was accordance with our results. Meanwhile, drug abuse could cause organ damage both in human and animal [34,35].…”

Section: Discussionsupporting

confidence: 91%

“…Knowledge on pharmacokinetics in plasma alone, therefore, is often not sufficient to estimate if certain bacterial pathogens can be killed at the infected site. Previous researches have studied the pharmacokinetics and penetration of moxifloxacin under different pathological state [4,5,6,7,8,9,10]. Only Stass [11] and Rink [12] have studied the pharmacokinetics of moxifloxacin in abdominal infection and reported that it has a good penetration into peritoneal exudates and abscess fluid in peritonitis and intra-abdominal abscess patients, respectively.…”

Section: Introductionmentioning

confidence: 99%

Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model

Zhu

Yang

Zhang

et al. 2015

Korean J Physiol Pharmacol

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The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intra-abdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in various tissues in intra-abdominal infected human. 12 male rats with intra-abdominal infections, induced by Escherichia coli, received a single dose of 40 mg/kg body weight of moxifloxacin. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK model was developed in rats and extrapolated to human using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration versus time profile of moxifloxcinin rats, Cmax was 11.151 µg/mL at 5 min after the intravenous injection and t1/2 was 2.936 h. Plasma concentration and kinetics in human were predicted and compared with observed datas. Moxifloxacin penetrated and accumulated with high concentrations in redmarrow, lung, skin, heart, liver, kidney, spleen, muscle tissues in human with intra-abdominal infection. The predicted tissue to plasma concentration ratios in abdominal viscera were between 1.1 and 2.2. When rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict drug pharmacokinetics and penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well as other tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacin due to its high concentration distribution. This pathological model extrapolation may provide reference to the PK/PD study of antibacterial agents.

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“…In the large-scale Eurodiale study, the outcome of DFIs in patients without PAD was relatively good, but particularly poor results were obtained in DFI patients with PAD [35]. As previously demonstrated, treatment with IV or PO moxifloxacin in DFI patients achieves a concentration well above MIC 90 for most pathogenic bacteria in peri-necrotic limb tissue [19], suggesting that PK/PD properties of moxifloxacin are able to overcome the potential lack of perfusion due to PAD.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of IV/PO moxifloxacin and IV piperacillin/tazobactam followed by PO amoxicillin/clavulanic acid in the treatment of diabetic foot infections: results of the RELIEF study

Schaper

Dryden

Kujath³

et al. 2012

Infection

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ObjectiveThe aim was to compare the efficacy and safety of two antibiotic regimens in patients with diabetic foot infections (DFIs).MethodsData of a subset of patients enrolled in the RELIEF trial with DFIs requiring surgery and antibiotics were evaluated retrospectively. DFI was diagnosed on the basis of the modified Wagner, University of Texas, and PEDIS classification systems. Patients were randomized to receive either intravenous/oral moxifloxacin (MXF, N = 110) 400 mg q.d. or intravenous piperacillin/tazobactam 4.0/0.5 g t.d.s. followed by oral amoxicillin/clavulanate 875/125 mg b.d. (PIP/TAZ–AMC, N = 96), for 7–21 days until the end of treatment (EOT). The primary endpoint was clinical cure rates in the per-protocol (PP) population at the test-of-cure visit (TOC, 14–28 days after EOT).ResultsThere were no significant differences between the demographic characteristics of PP patients in either treatment group. At TOC, MXF and PIP/TAZ–AMC had similar efficacy in both the PP and intent-to-treat (ITT) populations: MXF: 76.4 % versus PIP/TAZ–AMC: 78.1 %; 95 % confidence interval (CI) −14.5 %, 9.0 % in the PP population; MXF: 69.9 % versus PIP/TAZ–AMC: 69.1 %; 95 % CI −12.4 %, 12.1 % in the ITT population. The overall bacteriological success rates were similar in both treatment groups (MXF: 71.7 % versus PIP/TAZ–AMC: 71.8 %; 95 % CI −16.9 %, 10.7 %). A similar proportion of patients (ITT population) experienced any adverse events in both treatment groups (MXF: 30.9 % versus PIP/TAZ–AMC: 31.8 %, respectively). Death occurred in three MXF-treated patients and one PIP/TAZ–AMC-treated patient; these were unrelated to the study drugs.ConclusionMoxifloxacin has shown favorable safety and efficacy profiles in DFI patients and could be an alternative antibiotic therapy in the management of DFI. Clinical trial: NCT00402727.

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Pharmacokinetics and penetration of moxifloxacin into infected diabetic foot tissue in a large diabetic patient cohort

Cited by 14 publications

References 18 publications

Population pharmacokinetics and target attainment analysis of moxifloxacin in patients with diabetic foot infections

Population pharmacokinetics and target attainment analysis of moxifloxacin in patients with diabetic foot infections

Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model

Efficacy and safety of IV/PO moxifloxacin and IV piperacillin/tazobactam followed by PO amoxicillin/clavulanic acid in the treatment of diabetic foot infections: results of the RELIEF study

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