Monitoring serum concentrations for once-daily netilmicin dosing regimens

A once-daily dosing regimen for aminoglycosides is less expensive, at least as effective and possibly less toxic than multiple-daily dosing regimens. Once-daily dosing might also allow the frequency of measuring the serum concentrations of these antibiotics to be reduced since two of the major objectives of monitoring, high peak and low trough concentrations, are more likely to be achieved with this regimen. A novel strategy for monitoring serum concentrations which relies on a single sample obtained 8 h after a dose, as opposed to both trough and peak samples, is evaluated here. Serum kinetics of netilmicin were studied prospectively in 51 adult patients with initial serum creatinine concentrations of < 130 μmol/L who were treated with a median daily dosage of 400 mg. Concentrations measured 8 h after administration were within the target range of 1.5–6 mg/L in 113 of 134 dosing intervals studied. Concentrations above and below this range correlated significantly with higher and lower 24-h trough concentrations and areas under the curve respectively. There was also a significant correlation between 8-h netilmicin concentrations and nephrotoxicity (P < 0.05); a relative increase of ≧ 25% in the serum creatinine concentration or an absolute increase of > 25 μmol/L was detected in 0 of 7 patients with an 8-h concentration of < 1.5 mg/L, in 3 of 33 patients (9.1%) with an 8-h concentration of 1.5–6 mg/L and in 4 of 11 patients (36%) with an 8-h concentration of > 6 mg/L. The results of this study suggest that adequate information about serum netilmicin concentrations in patients receiving a once-daily dose may be derived from a sample obtained 8 h after administration.