Boussery, Koen

Colin, Pieter

Eleveld, Douglas J

Ruige, Johannes

Struys, Michel

T'jollyn, Huybrecht

Van Bocxlaer, Jan

Van Bortel, Lucas

English

Ghent University Academic Bibliography

MOXIFLOXACIN DOSING IN POST-BARIATRIC SURGERY PATIENTS:  ANOTHER NAIL IN THE COFFIN OF THE “ONE DOSE FITS ALL PARADIGM”. P.Colin1, D.J. Eleveld2, M.M.R.F. Struys 2,3, H.T’Jollyn1, L.M. Van Bortel4, J.Ruige5, J.Van Bocxlaer1, K.Boussery1.   1 Laboratory of Medical Biochemistry and Clinical Analysis , Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.  2 Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 3 Department of Anesthesia, Ghent University, Ghent, Belgium. 4 Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium. 5 Department Endocrinology and Metabolic Diseases, Ghent University Hospital, Ghent, Belgium. 1. Introduction & Objectives 2. Patients & Methods   Reference: Colin P, Eleveld D.J., Struys M.M.R.F, et al. Moxifloxacin dosing in post-bariatric surgery patients: another nail in the coffin of the “one dose fits all paradigm”. J Antimicrob Chemother Under review     Roux-en-Y gastric bypass surgery is the most commonly performed procedure for the treatment of morbid obesity. This anatomical alteration may affect the absorption and, consequently, the pharmacokinetic profile of oral drugs, possibly hampering therapeutic efficacy.  This study aims to (i) describe the pharmacokinetic variability of moxifloxacin concentrations in this cohort of healthy volunteers who have undergone gastric bypass using a population pharmacokinetic model and (ii) to assess the expected probability of target attainment (PTA) by MIC against a hypothetical Streptococcus pneumonia infection. Our study clearly emphasises the need for an individualized dosing of moxifloxacin in this patient population. Furthermore, throughout our PK-PD simulation study it became apparent that the development of a model based dosing regimen for moxifloxacin is hampered by the current discussion on which PK-PD target value to pursue when optimizing patient moxifloxacin therapy. 1De Smet J, Colin P, De Paepe P, et al. Oral bioavailability of moxifloxacin after Roux-en-Y gastric bypass surgery. J Antimicrob Chemother 2012; 67: 226-9. 3. Results (Pop-PK model) 4. Conclusion Figure 1: Observed moxifloxacin plasma-concentration time profiles after oral dosing. 3. Results (PK-PD simulation) In this modelling and simulation study we used data from a randomized cross-over trial on moxifloxacin pharmacokinetics previously published1.  In this trial, twelve volunteers, who had previously undergone bariatric surgery, received 2 single standard doses (intravenous and oral) of 400mg moxifloxacin administered on 2 occasions separated by a washout period of 1 week. Serial venous blood samples were drawn up to 72h after dosing and moxifloxacin plasma levels were measured by a validated high performance liquid chromatographic method with fluorescence detection. Population compartmental modelling and PK-PD simulations were performed using NONMEM®.  Table 1: Population parameter estimates of the final pharmacokinetic model and the associated 95% bootstrap confidence intervals calculated on 100 bootstrap samples. All model parameters except ka were centered for a typical subject with a LBM of 60 kg. 0.010.11100 12 24 36 48 60 72Time (h)Plasma concentration (µg/mL)0 2 4 6Figure 2: Predicted AUIC values after a standard 400mg oral dose versus the theoretical Streptococcus pneumonia MIC-values.   Simultaneously the AUIC cut-off values as proposed in literature are shown.  long dashes: AUICTotal = 100 target for bacterial eradication short dashed lines: AUICUnbound = 100; target for suppression of bacterial resistance formation. Figure 3: Predicted AUIC values for subjects with a LBM of 42 kg (open squares) and 78 kg (solid squares) after a standard 400mg oral dose versus the theoretical Streptococcus pneumonia MIC-values.  Population PTA PTA as function of LBM Clinical breakpoint EUCAST Clinical breakpoint EUCAST 

Moxifloxacin dosing in post-bariatric surgery patients: another nail in the coffin of the 'one dose fits all' paradigm

https://biblio.ugent.be/publication/4339110/file/4339121

Moxifloxacin dosing in post-bariatric surgery patients: another nail in the coffin of the 'one dose fits all' paradigm

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Ghent University Academic Bibliography