A study of once-daily amikacin with low peak target concentrations in intensive care unit patients: pharmacokinetics and associated outcomes.
OBJECTIVE
The aim of this study was to assess the pharmacokinetics of individualized amikacin single-dosage regimens targeting low peak serum concentrations in a population of intensive care unit (ICU) patients, and to describe the outcomes associated with this dosing strategy.


METHODS
In this prospective, noncomparative, pharmacokinetic study, 36 ICU patients with adequate renal function were treated with amikacin (intravenous infusion), in combination with other antibiotics, for hospital-acquired infections. The initial doses of amikacin were calculated based on individual creatinine clearance values whereas subsequent doses were calculated by using the amikacin pharmacokinetic parameters estimated from the serum concentration-time data of each individual patient (samples were drawn postinfusion, 1 h, 3 h, 6 h, and 10 h after the onset of the infusion and just before the next dose on days 2, 4, and 7 of therapy).


RESULTS
Results showed moderate only interpatient and lack of intrapatient (except for the volume of distribution) variability in amikacin pharmacokinetic parameters. There were no significant differences between achieved and target peak levels. Clinical response was noted in 94% and bacteriologic response was noted in 86% of patients. Nephrotoxicity did not occur during or after treatment.


CONCLUSIONS
Amikacin dosage individualization with low peak target concentrations was successful for the 36 ICU patients. This dosing strategy was not associated with nephrotoxicity, but conclusions on clinical efficacy cannot be drawn from this limited study.
Bacopoulou
Flora
F
Laboratory of Biopharmaceutics and Pharmacokinetics, Department of Pharmacy, University of Athens, Panepistimiopolis, Greece.
Markantonis
Sophia L
SL
Pavlou
Elias
E
Adamidou
Maria
M
D000151:Acinetobacter Infections / Q000188:drug therapy / Q000378:metabolism; D000328:Adult; D000583:Amikacin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D003404:Creatinine / Q000097:blood; D003428:Cross Infection / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008297:Male; D008657:Metabolic Clearance Rate; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000378:metabolism; D015163:Superinfection / Q000188:drug therapy / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000583:Amikacin; D003404:Creatinine