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Moxifloxacin dosing in post-bariatric surgery patients

Pieter Colin (UGent) , Douglas J Eleveld, Michel Struys (UGent) , Huybrecht T'jollyn (UGent) , Lucas Van Bortel (UGent) , Johannes Ruige (UGent) , Jan De Waele (UGent) , Jan Van Bocxlaer (UGent) and Koen Boussery (UGent)
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Abstract
Introduction Given the ever increasing number of obese patients and obesity related bypass surgery, dosing recommendations in the post-bypass population are needed. Using a population pharmacokinetic (PK) analysis and PK-pharmacodynamic (PD) simulations, we investigated whether adequate moxifloxacin concentrations are achieved in this population. Methods In this modelling and simulation study we used data from a trial on moxifloxacin PK. In this trial, volunteers who had previously undergone bariatric surgery (at least 6 months prior to inclusion), received two doses (intravenous and oral) of 400mg moxifloxacin administered on two occasions. Results In contrast to other papers, we found that moxifloxacin PK were best described by a three compartmental model using lean body mass (LBM) as a predictor for moxifloxacin clearance. Furthermore, we showed that the probability of target attainment for bacterial eradication against a hypothetical Streptococcus pneumoniae infection is compromised in patients with higher LBM, especially when targeting microorganisms with minimum inhibitory concentrations (MICs) of 0.5mgl-1 or higher (probability of target attainment (PTA) approaching zero). When considering the targets for suppression of bacterial resistance formation, even at MIC values as low as 0.25mgl-1, standard moxifloxacin dosing does not attain adequate levels in this population. Furthermore, for patients with a LBM of 78kg or higher, the probability of hitting this target approaches zero. Conclusions Throughout our PK-PD simulation study, it became apparent that, whenever optimal bacterial resistance suppression is deemed necessary, the standard moxifloxacin dosing will not be sufficient. Furthermore, our study emphasizes the need for a LBM based individualized dosing of moxifloxacin in this patient population.
Keywords
LEVOFLOXACIN, CIPROFLOXACIN, FLUOROQUINOLONES, PHARMACOKINETICS, HUMAN PLASMA, DRUG ABSORPTION, ORAL BIOAVAILABILITY, VITRO DYNAMIC-MODEL, RESISTANT STREPTOCOCCUS-PNEUMONIAE, GASTRIC BYPASS-SURGERY, pharmacokinetics, PK-PD, NONMEM, bariatric surgery, moxifloxacin

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Citation

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Chicago
Colin, Pieter, Douglas J Eleveld, Michel Struys, Huybrecht T’jollyn, Lucas Van Bortel, Johannes Ruige, Jan De Waele, Jan Van Bocxlaer, and Koen Boussery. 2014. “Moxifloxacin Dosing in Post-bariatric Surgery Patients.” British Journal of Clinical Pharmacology 78 (1): 84–93.
APA
Colin, Pieter, Eleveld, D. J., Struys, M., T’jollyn, H., Van Bortel, L., Ruige, J., De Waele, J., et al. (2014). Moxifloxacin dosing in post-bariatric surgery patients. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 78(1), 84–93.
Vancouver
1.
Colin P, Eleveld DJ, Struys M, T’jollyn H, Van Bortel L, Ruige J, et al. Moxifloxacin dosing in post-bariatric surgery patients. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY. 2014;78(1):84–93.
MLA
Colin, Pieter, Douglas J Eleveld, Michel Struys, et al. “Moxifloxacin Dosing in Post-bariatric Surgery Patients.” BRITISH JOURNAL OF CLINICAL PHARMACOLOGY 78.1 (2014): 84–93. Print.
@article{4210799,
  abstract     = {Introduction Given the ever increasing number of obese patients and obesity related bypass surgery, dosing recommendations in the post-bypass population are needed. Using a population pharmacokinetic (PK) analysis and PK-pharmacodynamic (PD) simulations, we investigated whether adequate moxifloxacin concentrations are achieved in this population. Methods In this modelling and simulation study we used data from a trial on moxifloxacin PK. In this trial, volunteers who had previously undergone bariatric surgery (at least 6 months prior to inclusion), received two doses (intravenous and oral) of 400mg moxifloxacin administered on two occasions. Results In contrast to other papers, we found that moxifloxacin PK were best described by a three compartmental model using lean body mass (LBM) as a predictor for moxifloxacin clearance. Furthermore, we showed that the probability of target attainment for bacterial eradication against a hypothetical Streptococcus pneumoniae infection is compromised in patients with higher LBM, especially when targeting microorganisms with minimum inhibitory concentrations (MICs) of 0.5mgl-1 or higher (probability of target attainment (PTA) approaching zero). When considering the targets for suppression of bacterial resistance formation, even at MIC values as low as 0.25mgl-1, standard moxifloxacin dosing does not attain adequate levels in this population. Furthermore, for patients with a LBM of 78kg or higher, the probability of hitting this target approaches zero. Conclusions Throughout our PK-PD simulation study, it became apparent that, whenever optimal bacterial resistance suppression is deemed necessary, the standard moxifloxacin dosing will not be sufficient. Furthermore, our study emphasizes the need for a LBM based individualized dosing of moxifloxacin in this patient population.},
  author       = {Colin, Pieter and Eleveld, Douglas J and Struys, Michel and T'jollyn, Huybrecht and Van Bortel, Lucas and Ruige, Johannes and De Waele, Jan and Van Bocxlaer, Jan and Boussery, Koen},
  issn         = {0306-5251},
  journal      = {BRITISH JOURNAL OF CLINICAL PHARMACOLOGY},
  language     = {eng},
  number       = {1},
  pages        = {84--93},
  title        = {Moxifloxacin dosing in post-bariatric surgery patients},
  url          = {http://dx.doi.org/10.1111/bcp.12302},
  volume       = {78},
  year         = {2014},
}

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