Population pharmacokinetics of imipenem in burn patients

Dailly, Éric; Pannier, Michel; Jolliet, Pascale; Bourin, Michel

doi:10.1046/j.1472-8206.2003.00190.x

Cited by 48 publications

(67 citation statements)

References 13 publications

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“…In patients with ventilator-associated pneumonia using the recommended daily dose (1 g) of ertapenem, bactericidal targets could not be attained for MIC values above 0.5 mg ⅐ liter Ϫ1 (4). This finding is in agreement with that of previous studies dealing with time-dependent antibiotics in ICU patients (6,12). This leads to the hypothesis that ertapenem at 1 g once daily may be underdosed in ICU patients with an increased distribution volume to achieve optimal concentrations in target tissues (3,11).…”

supporting

confidence: 83%

Penetration of Ertapenem into Muscle Measured by In Vivo Microdialysis in Mechanically Ventilated Patients

Boyadjiev

Boulaméry²,

Simon³

et al. 2011

Antimicrob Agents Chemother

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Ertapenem at 1 g once daily has been suggested to be underdosed in intensive care unit (ICU) patients to attain optimal concentrations in target tissues. Therefore, our study aimed to assess the kinetics of ertapenem in plasma and skeletal muscle in ICU patients using microdialysis. Average muscle free-ertapenem concentrations were above the MIC values of targeted pathogens. In a few patients, the concentrations were below the MIC values. The clinical efficiency of ertapenem at 1 g once daily should be evaluated in a large population of ICU patients.Ertapenem at 1 g once daily has been approved for the treatment of complicated intraabdominal, complicated skin and skin structure, acute pelvic, complicated urinary tract, and community-acquired infections (13,15). This has been supported by studies of tissue penetration in healthy volunteers (2,8). However, few studies have detailed ertapenem penetration in the intensive care unit (ICU) patient (1,3,4).The pharmacokinetics of drugs are modified in ICU patients due to the large daily fluid balance, acute changes in body weight, hypoalbuminemia, edema, and low hematocrit values, resulting in marked changes in elimination half-life (t 1/2 ), volume of distribution (V), and clearance (CL) (12,14). In patients with ventilator-associated pneumonia using the recommended daily dose (1 g) of ertapenem, bactericidal targets could not be attained for MIC values above 0.5 mg ⅐ liter Ϫ1 (4). This finding is in agreement with that of previous studies dealing with time-dependent antibiotics in ICU patients (6,12). This leads to the hypothesis that ertapenem at 1 g once daily may be underdosed in ICU patients with an increased distribution volume to achieve optimal concentrations in target tissues (3, 11). Our objective was to assess the kinetics of ertapenem in plasma and the interstitial space fluid of skeletal muscle in mechanically ventilated infected ICU patients.This study was performed in accordance with the Declaration of Helsinki (Edinburgh, Scotland, October 2000) and was approved by the local Ethics Committee. Written informed consent was obtained from a legal representative of each patient. The study was conducted as a single-center open trial. Patients admitted to the polyvalent ICU of Nord University Hospital (Marseilles, France) were eligible for inclusion if they met all of the following inclusion criteria: age between 18 and 80 years, mechanical ventilation, diagnosis of ventilator-associated pneumonia (VAP) or intraabdominal infection (IAI) due to a pathogen susceptible to ertapenem (Invanz; Merck Sharp & Dohme Laboratories, Paris, France), and informed consent signed by a relative. Patients with norepinephrinerefractory septic shock, positive hepatitis B virus surface antigen or HIV serology, pregnancy, a history of Clostridium difficile infection, known hypersensitivity to ertapenem, renal impairment (creatinine clearance of Յ30 ml/min/1.73 m 2 by the Cockroft and Gault formula), or a known contraindication for microdialysis probe insertion were not included. P...

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supporting

confidence: 83%

Penetration of Ertapenem into Muscle Measured by In Vivo Microdialysis in Mechanically Ventilated Patients

Boyadjiev

Boulaméry²,

Simon³

et al. 2011

Antimicrob Agents Chemother

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“…The significant relationships between pharmacokinetic parameters of doripenem and covariates, as reported in this paper, have been observed by others in population pharmacokinetic models for meropenem and imipenem (7,16,19,21). By way of example, the important impact of creatinine clearance on carbapenem clearance was reported by Dailly et al, who found that among the tested covariates (e.g., age, gender, body weight, height, and serum creatinine), serum creatinine (creatinine clearance) substantially affected the pharmacokinetic parameters of imipenem (7).…”

Section: Discussionmentioning

confidence: 54%

“…By way of example, the important impact of creatinine clearance on carbapenem clearance was reported by Dailly et al, who found that among the tested covariates (e.g., age, gender, body weight, height, and serum creatinine), serum creatinine (creatinine clearance) substantially affected the pharmacokinetic parameters of imipenem (7). Similarly, in a population pharmacokinetic analysis of meropenem, which included concentration data gathered from 79 adult patients (aged 18 to 93 years), Li et al determined that creatinine clearance, age, and body weight were the most significant covariates to affect meropenem pharmacokinetics.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Doripenem Based on Data from Phase 1 Studies with Healthy Volunteers and Phase 2 and 3 Studies with Critically Ill Patients

Nandy

Samtani

Lin

2010

Antimicrob Agents Chemother

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A population pharmacokinetic model of doripenem was constructed using data pooled from phase 1, 2, and 3 studies utilizing nonlinear mixed effects modeling. A 2-compartment model with zero-order input and first-order elimination best described the log-transformed concentration-versus-time profile of doripenem. The model was parameterized in terms of total clearance (CL), central volume of distribution (V c ), peripheral volume of distribution (V p ), and distribution clearance between the central and peripheral compartments (Q). The final model was described by the following equations (for jth subject): CL j (liters/h) ‫؍‬ 13. interindividual variability (percent coefficient of variation [% CV]) for CL (liters/h), V c (liters), V p (liters), and Q (liters/h) were 13.6 (19%), 11.6 (19%), 6.0 (25%), and 4.7 (42%), respectively. Residual variability, estimated using three separate additive residual error models, was 0.17 standard deviation (SD), 0.55 SD, and 0.92 SD for phase 1, 2, and 3 data, respectively. Creatinine clearance was the most significant predictor of doripenem clearance. Mean Bayesian clearance was approximately 33%, 55%, and 76% lower for individuals with mild, moderate, or severe renal impairment, respectively, than for those with normal renal function. The population pharmacokinetic model based on healthy volunteer data and patient data informs us of doripenem disposition in a more general population as well as of the important measurable intrinsic and extrinsic factors that significantly influence interindividual pharmacokinetic differences.

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“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] However, these methods have several disadvantages in terms of cost performance, time consumption and necessary equipment; for example, the use of expensive disposable cartridges at the solid-phase drug extraction, gradient elution control by a gradient HPLC pump system, and the ultraviolet detection at multiple wavelengths.…”

Section: Discussionmentioning

confidence: 99%

“…Both interday and intraday CVs for all drugs were less than 8.5%, which is similar to or much lower than previously reported values. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] Mean extraction recoveries varied from 81.2% (IDV) to 98.4% (APV). These results indicate that the method developed here achieves a high degree of reproducibility and accuracy.…”

Section: Discussionmentioning

confidence: 99%

Conventional HPLC Method Used for Simultaneous Determination of the Seven HIV Protease Inhibitors and Nonnucleoside Reverse Transcription Inhibitor Efavirenz in Human Plasma

Takahashi

Yoshida

Oki

et al. 2005

Biological & Pharmaceutical Bulletin

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Population pharmacokinetics of imipenem in burn patients

Cited by 48 publications

References 13 publications

Penetration of Ertapenem into Muscle Measured by In Vivo Microdialysis in Mechanically Ventilated Patients

Penetration of Ertapenem into Muscle Measured by In Vivo Microdialysis in Mechanically Ventilated Patients

Population Pharmacokinetics of Doripenem Based on Data from Phase 1 Studies with Healthy Volunteers and Phase 2 and 3 Studies with Critically Ill Patients

Conventional HPLC Method Used for Simultaneous Determination of the Seven HIV Protease Inhibitors and Nonnucleoside Reverse Transcription Inhibitor Efavirenz in Human Plasma

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