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. 2020 Apr 21;64(5):e02178-19.
doi: 10.1128/AAC.02178-19. Print 2020 Apr 21.

Population Pharmacokinetics of Amikacin Administered Once Daily in Patients with Different Renal Functions

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Population Pharmacokinetics of Amikacin Administered Once Daily in Patients with Different Renal Functions

Norma A Aréchiga-Alvarado et al. Antimicrob Agents Chemother. .

Abstract

The aim of this work was to evaluate the pharmacokinetics of amikacin in Mexican patients with different renal functions receiving once-daily dosing regimens and the influence of clinical and demographical covariates that may influence the optimization of this antibiotic. A prospective study was performed in a total of 63 patients with at least one determination of amikacin plasma concentration. Population pharmacokinetic (PK) parameters were estimated by nonlinear mixed-effects modeling; validations were performed for dosing recommendation purposes based on PK/pharmacodynamic simulations. The concentration-versus-time data were best described by a one-compartment open model with proportional interindividual variability associated with amikacin clearance (CL) and volume of distribution (V); residual error followed a homoscedastic trend. Creatinine clearance (CLCR) and ideal body weight (IBW) demonstrated significant influence on amikacin CL and V, respectively. The final model [CL (liters/h) = 7.1 × (CLCR/130)0.84 and V (liters) = 20.3 × (IBW/68)2.9] showed a mean prediction error of 0.11 mg/liter (95% confidence interval, -3.34, 3.55) in the validation performed in a different group of patients with similar characteristics. There is a wide variability in amikacin PK parameters in Mexican patients. This leads to inadequate dosing regimens, especially in patients with augmented renal clearance (CLCR of >130 ml/min). Optimization based on the final population PK model in Mexican patients may be useful, since reliability and clinical applicability have been demonstrated in this study.

Keywords: PK/PD modeling; amikacin; augmented renal clearance; population pharmacokinetics.

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Figures

FIG 1
FIG 1
Scatterplots of goodness of fit of population and individual predicted versus observed amikacin concentrations (including the identity line) for the final one-compartment open model for critically ill patients receiving amikacin administered once daily by intermittent intravenous infusion (n = 50).
FIG 2
FIG 2
Visual predictive check for amikacin plasma concentration-time profiles. Solid lines represent the median (red) and the 95th and 5th percentiles (blue) of the observations, which are overlapped by the 90% confidence intervals for the median (red area) and the 95th and 5th percentiles (blue areas) of the simulated profiles (n = 1,000).
FIG 3
FIG 3
Amikacin dose suggested for critically ill patients based on final population pharmacokinetic model and bacterial MIC (n = 1,000 PK/PD simulations).

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