Moxifloxacin dosing in post-bariatric surgery patients

摘要

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 400-mg 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 0.5-mg-l -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 0.25-mg-l-1, standard moxifloxacin dosing does not attain adequate levels in this population. Furthermore, for patients with a LBM of 78-kg 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.