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Clinical Pharmacokinetics

Published in:

01-08-2014 | Original Research Article

Levofloxacin Dosing Regimen in Severely Morbidly Obese Patients (BMI ≥40 kg/m²) Should Be Guided by Creatinine Clearance Estimates Based on Ideal Body Weight and Optimized by Therapeutic Drug Monitoring

Authors: Manjunath P. Pai, Piergiorgio Cojutti, Federico Pea

Published in: Clinical Pharmacokinetics | Issue 8/2014

Abstract

Background

Levofloxacin is a commonly prescribed antimicrobial where recommendations exist to reduce doses for renal impairment but not to increase doses for augmented renal function. Morbidly obese patients are increasing in prevalence, and represent a population that can have augmented renal function requiring higher-than-standard doses.

Objective

The current investigation was performed to characterize the pharmacokinetics (PK) and evaluate the influence of alternate body size descriptors and renal function as predictors of levofloxacin clearance (CL) and the area under the curve over 24 h (AUC₂₄).

Methods

A database of patients undergoing levofloxacin therapeutic drug monitoring (TDM) were queried to identify patients ≥18 years of age with a body mass index ≥40 kg/m². A maximum a posteriori probability Bayesian approach using a two-compartment linear PK model was used to estimate individual PK parameters and AUC₂₄.

Results

A total of 394 concentration-time data points (peaks and trough) from 68 patients between 98 and 250 kg were evaluated. The median (5th, 95th percentile) daily dose and AUC₂₄ was 1,000 (250, 1,500) mg and 90.7 (44.4, 228) mg·h/L, respectively. Levofloxacin CL was significantly (p < 0.05) related to height but not weight. As a result, levofloxacin CL was best related (R ² = 0.57) to creatinine CL (CLcr) estimated by the Cockcroft–Gault (CG) equation and ideal body weight (IBW) because IBW is a height transformation. An empiric four-category daily-dose regimen (500, 750, 1,000, 1,250 mg) stratified by CLcr (CG-IBW) is expected to have >90 % probability of achieving an AUC₂₄ of 50–150 mg·h/L in morbidly obese patients. Subsequent application of TDM and integration with pathogen-specific information could then be applied to tailor the levofloxacin regimen.

Conclusions

The proposed approach serves as a relevant alternative to the current fixed-dosing paradigm of levofloxacin in the morbidly obese.

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Title: Levofloxacin Dosing Regimen in Severely Morbidly Obese Patients (BMI ≥40 kg/m2) Should Be Guided by Creatinine Clearance Estimates Based on Ideal Body Weight and Optimized by Therapeutic Drug Monitoring
Authors: Manjunath P. Pai
Piergiorgio Cojutti
Federico Pea
Publication date: 01-08-2014
Publisher: Springer International Publishing
Published in: Clinical Pharmacokinetics / Issue 8/2014
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-014-0154-1

ACC 2024 Congress

Springer Medicine

Levofloxacin Dosing Regimen in Severely Morbidly Obese Patients (BMI ≥40 kg/m²) Should Be Guided by Creatinine Clearance Estimates Based on Ideal Body Weight and Optimized by Therapeutic Drug Monitoring

Abstract

Background

Objective

Methods

Results

Conclusions

ACC 2024 Congress

Springer Medicine

Abstract

Background

Objective

Methods

Results

Conclusions

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