Population Pharmacokinetics of Amikacin Administered Once Daily in Patients with Different Renal Functions
- PMID: 32041715
- PMCID: PMC7179627
- DOI: 10.1128/AAC.02178-19
Population Pharmacokinetics of Amikacin Administered Once Daily in Patients with Different Renal Functions
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.
Copyright © 2020 American Society for Microbiology.
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Comment in
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Urinary Creatinine Clearance and Pharmacokinetics Studies: If We Can Measure It, Why Do We Estimate It?Antimicrob Agents Chemother. 2020 Aug 20;64(9):e00980-20. doi: 10.1128/AAC.00980-20. Print 2020 Aug 20. Antimicrob Agents Chemother. 2020. PMID: 32571825 Free PMC article. No abstract available.
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