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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
Drugs in R&D - 17(2017), 1 vom: 07. März, Seite 177-187 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kato, Hideo [VerfasserIn] |
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| Anmerkungen: |
Date Completed 03.05.2017 Date Revised 04.11.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1007/s40268-016-0165-5 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM267771991 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Hagihara, Mao |e verfasserin |4 aut | |
| 700 | 1 | |a Hirai, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Sakanashi, Daisuke |e verfasserin |4 aut | |
| 700 | 1 | |a Suematsu, Hiroyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Nishiyama, Naoya |e verfasserin |4 aut | |
| 700 | 1 | |a Koizumi, Yusuke |e verfasserin |4 aut | |
| 700 | 1 | |a Yamagishi, Yuka |e verfasserin |4 aut | |
| 700 | 1 | |a Matsuura, Katsuhiko |e verfasserin |4 aut | |
| 700 | 1 | |a Mikamo, Hiroshige |e verfasserin |4 aut | |
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