Population pharmacokinetics of gentamicin in haemodialysis patients: modelling, simulations and recommendations
| Autor: | Caroline Monchaud, Vincent Allot, Jean-Baptiste Woillard, Julien Allard, Marie Essig, Pierre Marquet, Bénédicte Franck, Jean-Philippe Rerolle, Franck Saint-Marcoux |
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| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Urology Population pharmacokinetics Gentamicin Dose 030226 pharmacology & pharmacy Models Biological 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Renal Dialysis Medicine Humans Pharmacology (medical) Trough Concentration Chronic hemodialysis Computer Simulation 030212 general & internal medicine Dosing Dialysis Aged Pharmacology Aged 80 and over Creatinine business.industry General Medicine Middle Aged Anti-Bacterial Agents chemistry Gentamicin Female Gentamicins business Monte Carlo Method medicine.drug |
| Zdroj: | European journal of clinical pharmacology. 76(7) |
| ISSN: | 1432-1041 |
| Popis: | 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.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 1 mg/L for MIC values between 0.25 and 4 mg/L.A two-compartment model including the dialysis on the elimination constant and bodyweight on the volume of distribution best described the data. A 30-min gentamicin infusion of 2 mg/kg/day (for MIC = 1 mg/L) or 8 mg/kg/day (for MIC = 4 mg/L) just before dialysis eliminated by two dialysis sessions before the next administration (dose interval of at least 96 h) led to a peak 8*MIC for 90% of the simulations and a trough concentration 1 mg/L at 96 h for 92% and 34% respectively.The gentamicin dose generally used to treat infections in dialysis patients is insufficient and might be increased to 3-8 mg/kg/day just before dialysis, taking into account the type of infection. |
| Databáze: | OpenAIRE |
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