Cefepime and continuous renal replacement therapy (CRRT): In vitro permeability of two CRRT membranes and pharmacokinetics in four critically ill patients

Isla, Arantxazu; Rodríguez-Gascón, Alicia; Maynar, Javier; Arzuaga, Alazne; Toral, Darío; Pedraz, José Luís

doi:10.1016/j.clinthera.2005.05.004

Cited by 52 publications

(37 citation statements)

References 33 publications

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“…In a group of patients receiving ertapenem for ventilator-associated pneumonia (VAP), a two-to threefold variation was observed for peak concentration (C max ), VD, area under the curve (AUC), half-life (T 1/2 ), and CL [15]. Similar results were reported for teicoplanin [16•], cefepime [17], ceftazidime [18], levofl oxacin [11], linezolid [14], and colistin [19]. This variability raises questions about the appropriateness of the dose regimen administered, with a frequent risk of underdosage, and justifi es monitoring the agent as frequently as possible.…”

Section: Interpatient Variability and Variability Over Timesupporting

confidence: 79%

“…Cefepime (2 g IV every 8 hours) is signifi cantly removed by CVVH and CVVHDF procedures. The total amount of drug removed by hemofi ltration was 27.4% of the dose administered, and PK parameters (T 1/2 , VD) differed only slightly from those of previous publications; sieving co effi cient was fairly similar (0.76 ± 0.21) [17].…”

Section: Renal Failure and Renal Replacement Therapymentioning

confidence: 78%

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Pharmacokinetics of antibiotics or antifungal drugs in intensive care units

Dufour¹,

Montravers

2008

Curr Infect Dis Rep

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Intensive care unit (ICU) patients present several unusual pharmacokinetic (PK) characteristics compared with less seriously ill patients, including increased distribution volume and variable clearance. Interpatient PK variability is often considerable and can produce a wide range of values for PK parameters and major differences in drug exposure. These analyses have led to the development of simulation techniques and population PK models to assess dosing regimens in specific patient subsets. Plasma concentrations may frequently overestimate target-site concentrations and therefore clinical efficacy. The unbound drug concentration at the infection site should be preferred. Although renal replacement therapy techniques are commonly used in ICU patients, data concerning antibiotic dosing in this setting remain limited. Administration of antibacterial agents by continuous infusion is becoming a common technique to avoid undesirable high peak concentrations and low trough concentrations and to optimize PK-pharmacodynamic indices.

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Section: Interpatient Variability and Variability Over Timesupporting

confidence: 79%

Section: Renal Failure and Renal Replacement Therapymentioning

confidence: 78%

Pharmacokinetics of antibiotics or antifungal drugs in intensive care units

Dufour¹,

Montravers

2008

Curr Infect Dis Rep

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“…At least four out of six of the QC samples were within the 15% of their respective nominal values. The detailed pharmacokinetic assessment will be reported elsewhere [17,18]. Fig.…”

Section: Clinical Applicationsmentioning

confidence: 99%

Determination of ceftazidime and cefepime in plasma and dialysate-ultrafiltrate from patients undergoing continuous veno-venous hemodiafiltration by HPLC

Isla

Arzuaga

Maynar

et al. 2005

Journal of Pharmaceutical and Biomedical Analysis

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“…On the other hand clearance may be unchanged [17] or decreased [4,18] and in the presence of organ dysfunction such acute kidney injury, diminished clearance may lead to massive accumulation and toxicity [25][26][27]. In patients with renal dysfunction, optimization antibiotic dosing is further complicated by the use of renal replacement therapy which provides significant and variable extracorporeal clearance for several -lactams [28][29][30][31][32][33][34]. These pharmacokinetic challenges would mean that empiric fixed dose strategy is unlikely to ensure sufficient antibiotic exposure and as well empiric dose optimization is unrealistic due the little data available to guide clinicians.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of seven β-lactam antibiotics in human plasma for therapeutic drug monitoring and pharmacokinetic studies

Sime

Roberts

et al. 2014

Journal of Chromatography B

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThere is strong evidence in literature supporting the benefit of monitoring plasma concentrations of -lactam antibiotics in the critically ill to ensure appropriateness of dosing.The objective of this work was to develop a method for the simultaneous determination of total concentrations piperacillin, benzylpenicillin, flucloxacillin, meropenem, ertapenem, cephazolin and ceftazidime in human plasma. Sample preparation involved protein precipitation with acetonitrile containing 0.1% formic acid and subsequent dilution of supernatant with 0.1% formic acid in water. Chromatographic separation was achieved on a reversed phase column (C18, 2.6µm, 2.1* 50 mm) via gradient elution using water and acetonitrile, each containing 0.1% formic acid, as mobile phase. Tandem mass spectrometry (MSMS) analysis was performed, after electrospray ionization in the positive mode, with multiple reaction monitoring (MRM). The method is accurate with the inter-day and intra-day accuracies of quality control samples (QCs) ranging from 95%-107% and 95%-108%, respectively. It is also precise with intra-day and inter-day coefficient of variations ranging from 4 to 12 % and 5-14% respectively. The lower limit of quantification was 0.1g/mL for each antibiotic except flucloxacillin (0.25g/mL). Recovery was greater than 96% for all analytes except for ertapenem (78%). Coefficients of variation for the matrix effect were less than 10% over the six batches of plasma. Analytes were stable over three freeze-thaw cycles, and for reasonable hours on the bench top as well as post-preparation. This novel liquid chromatography tandem mass spectrometry method proved accurate, precise and applicable for therapeutic drug monitoring and pharmacokinetic studies of the selected -lactam antibiotics.Page 5 Highlights  We present a method for simultaneous determination of seven beta-lactams in plasma  The selected antibiotics are those commonly used in critically ill patients  The method is accurate, precise and meets validation requirements by guidelines  It proved applicable for therapeutic drug monitoring and pharmacokinetic studies

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Cefepime and continuous renal replacement therapy (CRRT): In vitro permeability of two CRRT membranes and pharmacokinetics in four critically ill patients

Cited by 52 publications

References 33 publications

Pharmacokinetics of antibiotics or antifungal drugs in intensive care units

Pharmacokinetics of antibiotics or antifungal drugs in intensive care units

Determination of ceftazidime and cefepime in plasma and dialysate-ultrafiltrate from patients undergoing continuous veno-venous hemodiafiltration by HPLC

Simultaneous determination of seven β-lactam antibiotics in human plasma for therapeutic drug monitoring and pharmacokinetic studies

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