Population pharmacokinetics of gentamicin in haemodialysis patients: modelling, simulations and recommendations

Purpose The usual recommended dose for gentamicin is 3 to 7 mg/kg/day for patients with a normal renal function while 1.7 mg/kg/day is recommended for patients undergoing chronic haemodialysis. The objectives of this study were to develop a population pharmacokinetics model (POPPK) for gentamicin, d...

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Veröffentlicht in:European journal of clinical pharmacology 2020-07, Vol.76 (7), p.947-955
Hauptverfasser: Franck, Bénédicte, Monchaud, Caroline, Saint-Marcoux, Franck, Rérolle, Jean-Philippe, Allard, Julien, Allot, Vincent, Marquet, Pierre, Essig, Marie, Woillard, Jean-Baptiste
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Sprache:eng
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Zusammenfassung:Purpose The usual recommended dose for gentamicin is 3 to 7 mg/kg/day for patients with a normal renal function while 1.7 mg/kg/day is recommended for patients undergoing chronic haemodialysis. The objectives of this study were to develop a population pharmacokinetics model (POPPK) for gentamicin, designed for patients undergoing dialysis, and to investigate the best dosing scheme for different MIC clinical breakpoints using Monte Carlo simulations. Methods In this monocentric prospective interventional open clinical study, 23 patients (141 gentamicin samples) were included. The covariates investigated were weight, creatinine, dialysis (yes/no), dialysis flow and dialysis duration. The POPPK model was developed in Pmetrics and 1000 time-concentration profiles were simulated for 9 doses between 2 and 10 mg/kg/day, with an inter-dose period of 24, 48 or 96 h to predict the probability of having both a serum peak > 8*MIC and a trough  8*MIC for > 90% of the simulations and a trough concentration
ISSN:0031-6970
1432-1041
DOI:10.1007/s00228-020-02867-3