Monitoring serum concentrations for once-daily netilmicin dosing regimens

Area of Science:

• Pharmacology
• Nephrology
• Clinical Pharmacy

Background:

• Once-daily aminoglycoside dosing offers cost, efficacy, and safety advantages over multiple daily doses.
• Monitoring aminoglycoside serum concentrations is crucial for optimizing therapy and minimizing toxicity.
• Traditional monitoring involves peak and trough levels, which may be cumbersome with once-daily regimens.

Purpose of the Study:

• To evaluate a novel strategy for monitoring netilmicin serum concentrations using a single sample obtained 8 hours post-dose.
• To assess the correlation between 8-hour netilmicin concentrations and therapeutic targets.
• To determine the relationship between 8-hour netilmicin concentrations and the incidence of nephrotoxicity.

Main Methods:

• Prospective study of 51 adult patients with normal renal function (creatinine < 130 mumol/L).
• Patients received a median daily dose of 400 mg of netilmicin.
• Serum netilmicin concentrations were measured 8 hours post-dose; correlations with 24-hour trough concentrations, AUC, and nephrotoxicity were analyzed.

Main Results:

• 8-hour post-dose concentrations were within the target range (1.5-6 mg/L) in 113 of 134 dosing intervals (84.3%).
• 8-hour concentrations correlated significantly with 24-hour trough levels and AUC.
• Nephrotoxicity showed a significant correlation with 8-hour netilmicin concentrations (P < 0.05), with higher rates observed at concentrations > 6 mg/L.

Conclusions:

• A single 8-hour post-dose serum concentration measurement is a viable strategy for monitoring once-daily netilmicin therapy.
• This simplified monitoring approach can help achieve therapeutic goals and predict potential nephrotoxicity.
• Optimized monitoring can enhance the safety and efficacy of once-daily aminoglycoside regimens.