Estimation of once-daily amikacin dose in critically ill adults

Abstract

This study aimed at investigating variables affecting amikacin pharmacokinetics in order to propose optimal initial dosing in critically ill adult patients treated with once-daily amikacin regimen. Amikacin pharmacokinetics was calculated based on plasma concentrations using one compartmental analysis. Relationships between pharmacokinetic parameters and demographic/clinical data were explored in linear regression models. Simulated dose and dosing intervals were derived from body size descriptors and estimated creatinine clearances for each patient. Amikacin volume of distribution best correlated with body surface area, while amikacin clearance was best predicted by CKD-EPI creatinine clearance. Our study suggests that dose of 517 mg per m² of body surface area leads to amikacin levels most approaching target peak concentration. Dosing interval calculated as 228.7 × e^{−3.08 × CKD-EPI creatinine clearance (mL s−1)} + 15.84 most closely approximated optimal dosing intervals based on individual pharmacokinetics. The dosing nomogram based on CKD-EPI creatinine clearance was designed.

Keywords:

• Amikacin
• Pharmacokinetics
• Body size descriptors
• Creatinine clearance
• Dosing
• Intensive care