Study of Efficacy and Safety in the Administration of 400 mg of Amikacin Sulfate Administered Once Daily to Elderly Patients / 医薬品情報学

ABSTRACT

<b>Objective: </b>In previously reported comparisons of aminoglycoside antimicrobials administered once daily versus multiple administration, toxicity was found to be equal or lower while efficiency remained high.  However, there are few reports on the clinical condition of targeted elderly persons.  The objective of this study was to evaluate the once-daily dosing regimen of 400 mg of AMK involving elderly pneumonia patients aged 75 years or older with regard to clinical evaluation including the efficacy and toxicity.<br><b>Methods: </b>A survey to clinically evaluate the efficacy and toxicity of 400 mg AMK administered once daily for 30 min at 24 h intervals was carried out.  One hundred twenty-seven patients with pneumonia and who were 75 years or older at Funabashi General Hospital were targeted, with the aim of an expected clinical effect of <i>C</i>_max/MIC≥ 8-10.  Serum concentration monitoring was carried out after administration began.<br><b>Results: </b>There were 121 patients (95.3%) of controlled AMK concentration with a trough serum concentration of <10 μg/mL, which is a safe concentration range.  There were 6 patients (4.7%) where trough serum concentration in the toxic range >10 μg/mL, with an average at 15.1±5.0 μg/mL, and the average administration days were 7.5 ± 3.3 days.  Moreover, before/after AMK administration, there were 3 patients (2.4%) where CRE values increased more than a 150% over the previous values, and were evaluated as renal dysfunction.  Average trough serum concentration at that time was 3.6 ± 1.1 μg/mL, and average number of days of administration were 13 ± 1.4 days.  Patients of trough serum concentration in the toxic range >10 μg/mL were not included.  The average peak serum concentration calculated by Winter’s pharmacokinetic parameter and the 1-compartment model was 35.3 ± 8.0 μg/mL, and the average <i>C</i>_max/MIC which correlates with the AMK effect was 9.9 ± 2.2.  The treatment was effective for 83 (65.4%) of the 127 patients.<br><b>Conclusion: </b>By once-daily administration of AMK 400 mg to aged persons 75 years or older, change in trough serum concentration into a safe range and <i>C</i>_max/MIC≥ 8-10, the level at which clinical effectivity can be expected, could be achieved.  This administration method is shown to be useful in maintaining AMK in the target serum concentration range for aged persons.