Extended-Interval Aminoglycoside (EIA) Regimen – Focus on Gentamicin and Amikacin
Date Issued
2004
Date
2004
Author(s)
Lai, Lily Li-Chun
DOI
en-US
Abstract
Extended-interval aminoglycoside (EIA) regimens, holding a number of properties, namely concentration-dependent bactericidal activity, post-antibiotic effect (PAE) and adaptive resistance, have been instituted to maximize therapeutic effects and to minimize the potential for toxicity.
The purpose of this retrospective study was to design an EIA regimen for gentamicin and amikacin based on the three properties mentioned above. This regimen aimed to comprise of a dose that achieves a serum peak concentration:minimum inhibitory concentration (peak concentration:MIC) ratio of 8:1 to 10:1 (target serum peak concentration of 16 to 20 mg/L for gentamicin and 32 to 40 mg/L for amikacin), and a dosing interval that achieves a balance between an 8-hour PAE period and a sufficient drug-free period of at least 4 hours.
A total of 205 datasets (110 in the gentamicin group and 95 in the amikacin group) were included in the analysis of this study. Individual pharmacokinetic profiles were determined, and population pharmacokinetic models were then developed. A 7-mg/kg dose of gentamicin and a 14-mg/kg dose of amikacin were required to achieve the target serum peak concentrations for patients with various degrees of renal function. However, only patients with creatinine clearance ≧70 mL/min for gentamicin and patients with creatinine clearance ≧60 mL/min for amikacin were able to obtain a sufficient drug-free period, not too long beyond the period covered by PAE, with a 24-hour dosing interval. Patients with creatinine clearance values below the cut-off points were therefore suggested to be maintained on the conventional dosing regimen as these individuals likely would not benefit from an EIA regimen.
Nonetheless, the appropriateness of the EIA regimen postulated in this study still waits for further clinical validation.
Subjects
藥品動態學參數
延長給藥間隔
藥物血中濃度變化曲線
胺基配醣體類抗生素
EIA
individual pharmacokinetic profiles
extended-interval aminoglycoside
population pharmacokinetic models
Type
text
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