Open AccessPopulation Pharmacokinetics of Amikacin Administered Once Daily in Patients with Different Renal Functions
Author(s) -
Norma A Aréchiga-Alvarado,
Susanna Edith MedellínGaribay,
Rosa del Carmen MilánSegovia,
Arturo Ortiz-Álvarez,
Martín Magaña-Aquino,
Silvia RomanoMoreno
Publication year - 2020
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.02178-19
Subject(s) - pharmacokinetics , amikacin , dosing , medicine , pharmacodynamics , pharmacology , renal function , population , antibiotics , population pharmacokinetics , intensive care medicine , biology , environmental health , microbiology and biotechnology
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 (CL CR ) and ideal body weight (IBW) demonstrated significant influence on amikacin CL and V , respectively. The final model [CL (liters/h) = 7.1 × (CL CR /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 (CL CR 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.