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Evaluation of Amikacin Pharmacokinetics and Pharmacodynamics for Optimal Initial Dosing Regimen
Amikacin has been one of the important antimicrobial agents against Gram-negative pathogens. However, there is discrepancy regarding the amikacin initial dosage, with some reports recently recommending ≥25 mg/kg and others the conventional dosage (15–20 mg/kg). Hence, we evaluated the optimal initia...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318333/ https://www.ncbi.nlm.nih.gov/pubmed/28063020 http://dx.doi.org/10.1007/s40268-016-0165-5 |
Sumario: | Amikacin has been one of the important antimicrobial agents against Gram-negative pathogens. However, there is discrepancy regarding the amikacin initial dosage, with some reports recently recommending ≥25 mg/kg and others the conventional dosage (15–20 mg/kg). Hence, we evaluated the optimal initial dosing regimen of amikacin. Pharmacokinetic (PK) parameters were estimated using a population PK analysis. The pharmacodynamic (PD) target was a ratio of ≥8 between the concentration achieved 1 h after beginning the infusion (C (peak)) and the minimal inhibitory concentration (MIC) of the liable bacteria. Based on the population PK parameters, we simulated individual C (peak) for several dosing regimens by Monte Carlo method and analyzed the C (peak)/MIC ratio for MICs from 0.5 to 32 μg/mL. This study included 35 infected patients (25 males), with a median (range) age and body weight of 70 (15–95) years and 49.5 (32.5–78) kg, respectively. A two-compartment model was used, and total body clearance (CL) significantly correlated with creatinine clearance, and volume of distribution (V (d)) with body weight. Regarding the probability to achieve a C (peak)/MIC of ≥8, the 15 mg/kg regimen was sufficient to achieve the PK/PD target in ≥90% of patients for a MIC of 4 μg/mL or less. The cumulative fraction of response in Pseudomonas aeruginosa was that 76% of patients achieved a C (peak)/MIC of 8 with the amikacin dosage of 15 mg/kg/day. We suggest that the 15-mg/kg once-daily dosage of amikacin be recommended as the initial dosage. As its maintenance dosage, the 15 mg/kg/day amikacin dosage is needed for a MIC of ≤4 μg/mL, and amikacin monotherapy for a MIC of ≥8 μg/mL should be avoided. |
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