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Amikacin once daily: a new dosing regimen based on drug pharmacokinetics
R Maller1, B M Emanuelsson, B Isaksson
1Department of Infectious Diseases, University Hospital, Linköping, Sweden.
Abstract:
Once-daily dosing of amikacin is a novel therapy regimen which seems pharmacokinetically appropriate for the primary group of patients considered for aminoglycoside therapy. In this study of 29 elderly patients with serious infections, amikacin 11 mg/kg or 15 mg/kg bw was administered as a short-term (30 min) intravenous infusion. The amikacin serum concentration-time profile was best described by a bi-exponential equation with a half-life of about 4.8 h. A triexponential equation was not applicable because the slow terminal elimination phase was not detected during the 24 h dosing interval. In practice, a uni-exponential equation is often used, and this may lead to incorrect conclusions about the elimination rate of amikacin. Amikacin clearance provides more direct information about elimination of amikacin than does serum half-life. Thus, there was a better correlation between the individual amikacin clearances and creatinine clearances (r = 0.89), than between the serum half-lives of amikacin and the creatinine clearances (r = 0.71). For elderly patients a smaller dose of amikacin than the regular daily dose of 15 mg/kg bw, i.e. about 11 mg/kg bw, seems recommendable, when it is given once daily. From the data obtained it is also obvious that once-daily dosing of amikacin does not eliminate the need for checking serum concentrations of the drug.
Insights
Once-daily amikacin dosing is suitable for elderly patients with serious infections. For this population, an 11 mg/kg dose is recommended over 15 mg/kg, and serum concentration monitoring remains essential.
Area of Science:
- Pharmacology
- Nephrology
- Infectious Diseases
Background:
- Aminoglycoside therapy, including amikacin, is crucial for serious infections.
- Once-daily dosing regimens are increasingly explored for pharmacokinetic appropriateness.
- Elderly patients present unique challenges in drug dosing due to physiological changes.
Purpose of the Study:
- To evaluate the pharmacokinetic appropriateness of once-daily amikacin dosing in elderly patients.
- To compare amikacin elimination kinetics with renal function (creatinine clearance).
- To determine optimal amikacin dosage for elderly patients receiving once-daily administration.
Main Methods:
- A study involving 29 elderly patients with serious infections.
- Administration of amikacin at 11 mg/kg or 15 mg/kg body weight via short-term intravenous infusion.
- Analysis of amikacin serum concentration-time profiles using bi-exponential and uni-exponential equations.
- Correlation analysis between amikacin clearance, amikacin half-life, and creatinine clearance.
Main Results:
- Amikacin serum concentration-time profiles were best described by a bi-exponential equation with a half-life of approximately 4.8 hours.
- A strong correlation was observed between individual amikacin clearances and creatinine clearances (r = 0.89).
- A weaker correlation was found between amikacin serum half-lives and creatinine clearances (r = 0.71).
Conclusions:
- Once-daily amikacin dosing is pharmacokinetically feasible in elderly patients.
- An 11 mg/kg once-daily dose appears more appropriate for elderly patients than the standard 15 mg/kg.
- Amikacin clearance is a more reliable indicator of elimination in this population than serum half-life, and monitoring is still necessary.