Evaluation of Current Amikacin Dosing Recommendations and Development of an Interactive Nomogram: The Role of Albumin

Abstract

This study aimed to evaluate the potential efficacy and safety of the amikacin dosage proposed by the main guidelines and to develop an interactive nomogram, especially focused on the potential impact of albumin on initial dosage recommendation. The probability of target attainment (PTA) for each of the different dosing recommendations was calculated through stochastic simulations based on pharmacokinetic/pharmacodynamic (PKPD) criteria. Large efficacy and safety differences were observed for the evaluated amikacin dosing guidelines together with a significant impact of albumin concentrations on efficacy and safety. For all recommended dosages evaluated, efficacy and safety criteria of amikacin dosage proposed were not achieved simultaneously in most of the clinical scenarios evaluated. Furthermore, a significant impact of albumin was identified: The higher is the albumin, (i) the higher will be the PTA for maximum concentration/minimum inhibitory concentration (Cmax/MIC), (ii) the lower will be the PTA for the time period with drug concentration exceeding MIC (T>MIC) and (iii) the lower will be the PTA for toxicity (minimum concentration). Thus, accounting for albumin effect might be of interest for future amikacin dosing guidelines updates. In addition, AMKnom, an amikacin nomogram builder based on PKPD criteria, has been developed and is freely available to help evaluating dosing recommendations.

Keywords

• amikacin dosing recommendations guidelines
• albumin
• nomogram
• model-informed precision dosing
• pharmacokinetics/pharmacodynamics