Experience of once-daily aminoglycoside dosing using a target area under the concentration-time curve

Many centres are changing to once-daily aminoglycoside administration. However, proposed methods for this practice often have theoretical and practical difficulties. We have developed a method in which a target area under the concentration-time curve (AUC) is used instead of traditional peak and trough serum concentrations.

To analyse our experience with the target AUC method in the first 100 courses of once-daily aminoglycoside administration in the Christchurch, New Zealand hospitals.

Following a starting dose of 5-7 mg/kg, administered by 30-minute infusion, the AUC was calculated using two serum aminoglycoside concentrations taken at one and six-14 hours after the start of the infusion. Dose adjustment was made to correct for any difference between the calculated AUC and a target AUC (72-101 mg.1(-1).h). The method was assessed for practicality and precision in 100 courses of treatment. The incidence of aminoglycoside toxicity was documented.

The mean final dose of 6.68 mg/kg, and AUC of 92.8 mg.1(-1).h, were significantly different from the mean starting dose and AUC of 5.67 mg/kg and 74.0 mg.1(-1).h, respectively. The method appeared to be more precise than empirical dosing at achieving the target AUC even though the final recommended dose had more variability than the starting dose. Although the study was uncontrolled, observed nephrotoxicity (2%) and ototoxicity (up to 6.9%) were no greater than expected from the results of other studies. There were no deaths related to antibiotic failure.

The AUC method was practical, and more appropriate for once-daily dosing than the conventional method of aiming for target peak and trough concentrations. Dose adjustment can be made before the next dose.