Predictive performance of a gentamicin population pharmacokinetic model in two western populations of critically ill patients
Résumé
External validation of population pharmacokinetic (PK) models is warranted before they can be clinically applied to aid in antibiotic dose selection. The primary objective of this study was to assess the predictive performance of a gentamicin population PK model in intensive care unit (ICU) patients in two independent western populations of critically ill patients. METHODS: Data were collected from the ICU where the model was developed (Academic Medical Centre, Amsterdam [AMC]) and from the Centre Hospitalier Universitaire de N\ⁱmes (CHU N\ⁱmes). Primary endpoints were bias and accuracy. The model was regarded as valid if bias was not significantly different from 0 and accuracy was equal to or less than 2.5 mg/L. Non-linear mixed-effects modelling (NONMEM) was used for data analysis. RESULTS: The AMC validation dataset consisted of 192 samples from 66 ICU patients and the CHU N\ⁱmes dataset of 230 gentamicin samples from 50 ICU patients. The structural model predicted the gentamicin plasma concentrations in the AMC population with a non-significant bias (0.35, 95%CI: -0.11-0.81) and a sufficient accuracy of 2.5 mg/L (95%CI: 2.3-2.8). The gentamicin plasma concentrations were overpredicted in the CHU N\ⁱmes population with a significant bias of 4.8 mg/L (95%CI: 4.00-5.62) and an accuracy of 5.5 mg/L (95%CI: 4.7-6.2). CONCLUSION: The model is valid for use in the AMC ICU population but not in the CHU N\ⁱmes ICU population. This illustrates that caution is needed when using a population PK model in an external population.
Mots clés
Humans
Female
Male
Aged
Drug Administration Schedule
Middle Aged
Anti-Bacterial Agents
Intensive Care Units
Models
Statistical
Area Under Curve
Critical Illness
Acute Kidney Injury
Hemodiafiltration
Drug Dosage Calculations
gentamicin
Gentamicins
hypoalbuminemia
population pharmacokinetics
predictive performance