Pharmacokinetics of moxifloxacin in non-inflamed cerebrospinal fluid of humans: implication for a bactericidal effect

Kanellakopoulou, Kyriaki; Pagoulatou, Alexandra; Stroumpoulis, Konstantinos; Vafiadou, M.; Kranidioti, Hariklia; Giamarellou, Helen; Giamarellos‐Bourboulis, Evangelos J.

doi:10.1093/jac/dkn110

Cited by 47 publications

(30 citation statements)

References 18 publications

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“…111-113 Indeed, fluoroquinolones achieve far higher CSF:plasma ratios than other antimicrobial classes, with values averaging ~0.50, 114-116 versus ~0.10 for beta-lactams (range, 0.007 – 0.25), 117-123 ~0.15 for vancomycin, 124 and ~0.20 for aminoglycosides 108 in intact meninges. With inflammation, however, the tight junctions that connect cerebral endothelial cells become more porous, allowing up to an order of magnitude higher CSF penetration for hydrophilic compounds.…”

Section: Antimicrobial Pharmacokineticsmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Principles of Anti-infective Dosing

Onufrak

Forrest

González

2016

Clinical Therapeutics

127

104

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Purpose An understanding of the pharmacokinetic (PK) and pharmacodynamic (PD) principles that determine response to antimicrobial therapy can provide the clinician with better-informed dosing regimens. Factors influential on antibiotic disposition and clinical outcome are presented, with a focus on the primary site of infection. Techniques to better understand antibiotic PK and optimize PD are acknowledged. Methods PubMed (inception – April 2016) was reviewed for relevant publications assessing antimicrobial exposures within different anatomical locations and clinical outcomes for various infection sites. Findings A limited literature base indicates variable penetration of antibiotics to different target sites of infection, with drug solubility and extent of protein binding providing significant PK influences in addition to the major clearing pathway of the agent. PD indices derived from in vitro and animal models determine the optimal magnitude and frequency of dosing regimens for patients. PK/PD modeling and simulation has been shown an efficient means of assessing these PD endpoints against a variety of PK determinants, clarifying the unique effects of infection site and patient characteristics to inform the adequacy of a given antibiotic regimen. Implications Appreciation of the PK properties of an antibiotic and its PD measure of efficacy can maximize the utility of these life-saving drugs. Unfortunately, clinical data remains limited for a number of infection site-antibiotic exposure relationships. Modeling and simulation can bridge preclinical and patient data for the prescription of optimal antibiotic dosing regimens, consistent with the tenets of personalized medicine.

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Section: Antimicrobial Pharmacokineticsmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Principles of Anti-infective Dosing

Onufrak

Forrest

González

2016

Clinical Therapeutics

127

104

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“…Among the newer fluoroquinolones (e.g., levofloxacin, gatifloxacin, moxifloxacin, clinafloxacin, gemifloxacin, and garenoxacin), moxifloxacin, in particular, has an excellent CSF penetration (50 --85%) and its penetration into the CSF was only slightly reduced by concomitant dexamethasone therapy [85][86][87]. It was as effective as ceftriaxone and vancomycin against penicillin-resistant pneumococcus in experimental meningitis [85], but clinical data is lacking.…”

Section: Moxifloxacinmentioning

confidence: 99%

Treatment of bacterial meningitis: an update

Shin

Kim

2012

Expert Opinion on Pharmacotherapy

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Prompt treatment of bacterial meningitis with an appropriate antibiotic is essential. Optimal antimicrobial treatment of bacterial meningitis requires bactericidal agents able to penetrate the blood-brain barrier (BBB), with efficacy in cerebrospinal fluid (CSF). Several new antibiotics have been introduced for the treatment of meningitis caused by resistant bacteria, but their use in human studies has been limited. More complete understanding of the microbial and host interactions that are involved in the pathogenesis of bacterial meningitis and associated neurologic sequelae is likely to help in developing new strategies for the prevention and therapy of bacterial meningitis.

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“…Rodriguez-Cerrato et al determined moxifloxacin CSF penetration in a rabbit model of Escherichia coli meningitis [14]. Kanellakopoulou et al showed the pharmacokinetics of moxifloxacin in noninflamed CSF of humans [13, 14]. These two studies investigated moxifloxacin pharmacokinetics in CSF.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the intracellular development of L. monocytogenes , it seems more relevant to measure moxifloxacin concentrations in CNS tissue rather than in cerebrospinal fluid (CSF) [13, 14]. However, no bioanalytical assay has been performed to determine moxifloxacin concentrations in brain tissue (CNS).…”

Section: Introductionmentioning

confidence: 99%

High-Performance Liquid Chromatography Assay for Moxifloxacin in Brain Tissue and Plasma: Validation in a Pharmacokinetic Study in a Murine Model of Cerebral Listeriosis

Respaud

Grayo

Singlas

et al. 2012

Journal of Analytical Methods in Chemistry

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Moxifloxacin is a broad-spectrum antibacterial 8-methoxy-fluoroquinolone. In order to evaluate the pharmacokinetic properties of moxifloxacin in mouse plasma and brain tissue, we developed a high-performance liquid chromatography (HPLC) method. This study was based on single-drug delivery, intravenously dosed in a central listeriosis murine model. The method employed a reversed-phase Lichrospher RP-18 with a precolumn (250×4.6 mm) and a mobile phase composed of a mixture of acetonitrile, methanol, and citric buffer (pH=3.5) with sodium dodecyl sulfate and tetrabutylammonium bromide. Fluorescence detection was performed at an excitation wavelength of 290 nm and an emission wavelength of 550 nm. The relative standard deviation of intra- and inter-day assays was <10%. This validated method led to a short retention time (8.0 min) for moxifloxacin. The standard curves were linear from 5–250 μg/L in plasma and from 0.1–2.5 μg/g of brain tissue. The limits of quantification were 5 μg/L in plasma and 0.1 μg/g in brain tissue. The method enabled the detection of systemic antimicrobial in plasma and in CNS inListeria-infected mice. Injected moxifloxacin passed through the encephalic barrier within a 30 to 60 min after injection time frame. Moxifloxacin pharmacokinetics are modeled in an infected model compared to control mice.

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Pharmacokinetics of moxifloxacin in non-inflamed cerebrospinal fluid of humans: implication for a bactericidal effect

Cited by 47 publications

References 18 publications

Pharmacokinetic and Pharmacodynamic Principles of Anti-infective Dosing

Pharmacokinetic and Pharmacodynamic Principles of Anti-infective Dosing

Treatment of bacterial meningitis: an update

High-Performance Liquid Chromatography Assay for Moxifloxacin in Brain Tissue and Plasma: Validation in a Pharmacokinetic Study in a Murine Model of Cerebral Listeriosis

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