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Because the sepsis-induced pharmacokinetic (PK) modifications need to be considered in aminoglycoside dosing, the present study aimed to develop a population PK model for amikacin (AMK) in severe sepsis and to subsequently propose an optimal sampling strategy suitable for Bayesian estimation of the drug PK parameters. Concentration-time profiles for AMK were obtained from 88 critically ill septic patients during the first 24 hours of antibiotic treatment. The population PK model was developed using a nonlinear mixed effects modeling approach. Covariate analysis included demographic data, pathophysiological characteristics, and comedication. Optimal sampling times were selected based on a robust Bayesian design criterion. Taking into account clinical constraints, a two-point sampling approach was investigated. A two-compartment model with first-order elimination best fitted the AMK concentrations …