Pharmacokinetics of ertapenem in burns patients

Dailly, Éric; Arnould, J.F.; Fraissinet, François; Naux, E.; Bouralière, M.A. Letard de la; Bouquié, Regis; Deslandes, Guillaume; Jolliet, Pascale; Floch, R. Le

doi:10.1016/j.ijantimicag.2013.02.021

Cited by 12 publications

(10 citation statements)

References 13 publications

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“…All pharmacokinetic calculations were performed using the MW/Pharm software package (version 3.82; Mediware, Zuidhorn, The Netherlands). On the basis of the findings presented in previous reports and the findings of recent pharmacokinetic studies of ertapenem (10)(11)(12)(13)(14)(15)(16)(17)(23)(24)(25), concentration-time curves were evaluated in one-compartment and two-compartment models. The final model was selected on the basis of the AIC (27).…”

Section: Methodsmentioning

confidence: 99%

“…The plasma drug concentrations for the 42 healthy volunteers were used to develop a two-compartment population pharmacokinetic model using an iterative two-stage Bayesian (ITSB) procedure (the KinPop module of the MW/Pharm software package) (22). Clearance (CL) was calculated using the equation (CL m · BSA)/(1.85 ϩ f r · CL CR ), where CL m is metabolic clearance (in liters per hour per 1.85 m 2 ), BSA is the body surface area (in square meters), f r is the drug clearance/creatinine clearance ratio, and CL CR is creatinine clearance (in liters per hour) (23). Pharmacokinetic parameters were assumed to be log normally distributed, and the residual error was assumed to be normally distributed.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetic Modeling and Limited Sampling Strategies Based on Healthy Volunteers for Monitoring of Ertapenem in Patients with Multidrug-Resistant Tuberculosis

Rijn

Zuur

Altena

et al. 2017

Antimicrob Agents Chemother

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Ertapenem is a broad-spectrum carbapenem antibiotic whose activity against Mycobacterium tuberculosis is being explored. Carbapenems have antibacterial activity when the plasma concentration exceeds the MIC at least 40% of the time (40% T MIC ). To assess the 40% T MIC in multidrug-resistant tuberculosis (MDR-TB) patients, a limited sampling strategy was developed using a population pharmacokinetic model based on data for healthy volunteers. A two-compartment population pharmacokinetic model was developed with data for 42 healthy volunteers using an iterative two-stage Bayesian method. External validation was performed by Bayesian fitting of the model developed with data for volunteers to the data for individual MDR-TB patients (in which the fitted values of the area under the concentrationtime curve from 0 to 24 h [AUC 0 -24, fit values] were used) using the population model developed for volunteers as a prior. A Monte Carlo simulation (n ϭ 1,000) was used to evaluate limited sampling strategies. Additionally, the 40% T MIC with the free fraction (f 40% T MIC ) of ertapenem in MDR-TB patients was estimated with the population pharmacokinetic model. The population pharmacokinetic model that was developed was shown to overestimate the area under the concentration-time curve from 0 to 24 h (AUC 0 -24 ) in MDR-TB patients by 6.8% (range, Ϫ17.2 to 30.7%). The best-performing limited sampling strategy, which had a time restriction of 0 to 6 h, was found to be sampling at 1 and 5 h (r 2 ϭ 0.78, mean prediction error ϭ Ϫ0.33%, root mean square error ϭ 5.5%). Drug exposure was overestimated by a mean percentage of 4.2% (range, Ϫ15.2 to 23.6%). When a free fraction of 5% was considered and the MIC was set at 0.5 mg/liter, the minimum f 40% T MIC would have been exceeded in 9 out of 12 patients. A population pharmacokinetic model and limited sampling strategy, developed using data from healthy volunteers, were shown to be adequate to predict ertapenem exposure in MDR-TB patients.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic Modeling and Limited Sampling Strategies Based on Healthy Volunteers for Monitoring of Ertapenem in Patients with Multidrug-Resistant Tuberculosis

Rijn

Zuur

Altena

et al. 2017

Antimicrob Agents Chemother

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“…The pharmacokinetics of ertapenem, the most narrow spectrum carbapenem, were recently documented in a study by Dailly et al 24 Because ertapenem is a highly protein-bound drug, it could be anticipated that burn injury would have a stronger effect on PK than for agents with minimal protein binding, including the other carbapenems. However, the V d and t 1/2 observed among the burn population were only slightly elevated as compared to the previously reported data from healthy volunteers (9.7 vs 8.2 L; 5.33 vs 3.8 h) and the CL T of ertapenem was lower (22.2 vs 29.5 ml/minute) among the burn patients.…”

Section: Carbapenemsmentioning

confidence: 99%

“…Healthy volunteers Aztreonam 2 g Q 6 hrs 22 (2 g Q 12 hrs in one patient) 8 49% Aztreonam 2 g × one dose 23,62 8 Healthy volunteers Ertapenem 1 g daily × two doses 24 8 38.5% Ertapenem 1 g × one dose 25 6 Meropenem 0.5-1 g Q 8-12 hrs 26 59 49.3% Meropenem 1 g × one dose 27, 63 12 Healthy volunteers Imipenem 0.5 g Q 6 hrs 29 11 43.4% Imipenem 0.5 g Q 6 hrs 64 47 27.6% Imipenem 1 g Q 6 hrs 30, 65 6 Healthy volunteers Gentamicin 1.5-2 mg/kg × one dose, then 1 mg/kg Q8h or 3 mg/kg daily 66 6 34.6% Gentamicin and tobramycin 5-7 mg/kg daily 34 40 37% Gentamicin 7 mg/kg × one dose 33, 67 11 Healthy volunteers Tobramycin 80-350 mg daily 68 23 53% Tobramycin 1 mg/kg × one dose 67, 69 11 Healthy volunteers Amikacin 20 mg/kg daily 35 38 27% Amikacin 15 mg/kg × one dose 67, 70 6 Healthy volunteers Vancomycin 2-6g daily 36 10 Healthy volunteers Daptomycin 6 mg/kg Vancomycin 750 mg Q one dose 41 9 34% Daptomycin 6 mg/kg daily 42, 73 6 Healthy volunteers Linezolid 600 mg × one dose 45 8 41% Linezolid 600 mg × one dose 45 %T>MIC and C max /MIC, and many drugs, such as the fluoroquinolones and daptomycin may have optimal efficacy described by multiple PD parameters. One of the most commonly studied medications that relies on optimization of this PD parameter is vancomycin with an AUC/MIC target of at least 400 for methicillin-resistant Staphylococcus aureus best correlating with positive clinical outcomes.…”

mentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Antibacterial and Antifungal Agents in Adult Patients With Thermal Injury

Ortwine

Pogue

Faris

2015

Journal of Burn Care & Research

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Patients with significant thermal injury are at a high risk for developing bacterial and fungal infections due to the loss of protective integument and often require lengthy treatment courses with anti-infective agents. Dosing of these agents in the burn population is challenging as these patients experience changes in their physiology around 48 hours postinjury. These changes include increased cardiac output, increased blood flow to the kidneys and liver, and decreased albumin production. These alterations in the physiology can lead to an increased drug clearance, higher volumes of distribution, and increased or decreased total drug exposure. Currently, there are no guidelines describing the most ideal method of dosing anti-infectives in this population, and most studies that have been published include only a small number of patients. The purpose of this review is to summarize the existing literature regarding the pharmacokinetics and pharmacodynamics of antibiotics and antifungal agents in the burn population and to provide dosing suggestions whenever possible. Not all antibiotics and antifungal agents have been studied, and further research is needed in this area in order to provide optimal care for patients with thermal injury.

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“…Due to this high variability in pharmacokinetic parameters, exposure of ertapenem might be suboptimal in these specific populations (5)(6)(7)(8)(9)(10). Since ertapenem is a time-dependent antibiotic, therapeutic drug monitoring (TDM) should therefore be considered, when this drug is used in specific populations, to achieve optimal bactericidal activity and optimize drug-dosing regimens.…”

mentioning

confidence: 99%

Quantification and Validation of Ertapenem Using a Liquid Chromatography-Tandem Mass Spectrometry Method

Rijn

Wessels

Greijdanus

et al. 2014

Antimicrob Agents Chemother

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Ertapenem, a carbapenem, relies on time-dependent killing. Therapeutic drug monitoring (TDM) should be considered, when ertapenem is used in specific populations, to achieve optimal bactericidal activity and optimize drug-dosing regimens. No validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been reported using deuterated ertapenem as the internal standard. A new simple and robust LC-MS/MS method using a quadrupole mass spectrometer was developed for analysis of ertapenem in human plasma, using deuterated ertapenem as the internal standard. The calibration curve was linear over a range of 0.1 (lower limit of quantification [LLOQ]) to 125 mg/liter. The calculated accuracy ranged from ؊2.4% to 10.3%. Within-run coefficients of variation (CV) ranged from 2.7% to 11.8%, and between-run CV ranged from 0% to 8.4%. Freezethaw stability had a bias of ؊3.3% and 0.1%. Storage of QC samples for 96 h at 4°C had a bias of ؊4.3 to 5.6%, storage at room temperature for 24 h had a bias of ؊10.7% to ؊14.8%, and storage in the autosampler had a bias between ؊2.9% and ؊10.0%. A simple LC-MS/MS method to quantify ertapenem in human plasma using deuterated ertapenem as the internal standard has been validated. This method can be used in pharmacokinetic studies and in clinical studies by performing TDM.

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Pharmacokinetics of ertapenem in burns patients

Cited by 12 publications

References 13 publications

Pharmacokinetic Modeling and Limited Sampling Strategies Based on Healthy Volunteers for Monitoring of Ertapenem in Patients with Multidrug-Resistant Tuberculosis

Pharmacokinetic Modeling and Limited Sampling Strategies Based on Healthy Volunteers for Monitoring of Ertapenem in Patients with Multidrug-Resistant Tuberculosis

Pharmacokinetics and Pharmacodynamics of Antibacterial and Antifungal Agents in Adult Patients With Thermal Injury

Quantification and Validation of Ertapenem Using a Liquid Chromatography-Tandem Mass Spectrometry Method

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