Clinical use of a one-compartment model for determining netilmicin pharmacokinetic parameters and dosage...

To determine netilmicin pharmacokinetic parameters and to evaluate the use of a one-compartment pharmacokinetic model, 32 patients receiving netilmicin for suspected gram-negative sepsis were enrolled in our study protocol. Dose and dosage interval for each patient were determined by one-compartment pharmacokinetic analysis of six postinfusion netilmicin serum samples (0.16, 0.33, 0.5, 1, 2, and 3 h) measured by radioimmunoassay. In patients with a normal serum creatinine, mean (+/- SD) half-life and distribution volume were 1.9 +/- 1.1 h and 0.2 +/- 0.8 L/kg, respectively. The average daily dose and mean days of therapy were 5.1 +/- 1.9 mg/kg/day for 7.3 +/- 2.8 days. Serum creatinine changes of greater than 0.5 mg% occurred in 2 of 28 (7%) patients. Substantial variability in half-life and distribution volume occurred in patients. Initial dosages of 5-7 mg/kg/day in divided dosages seem appropriate for adult patients with normal renal function. Monitoring of serum levels and adjustment of dose and dosage interval are necessary to maintain therapeutic antibiotic concentrations. As with other aminoglycosides, the one-compartment pharmacokinetic model proved to be an acceptable method for measuring netilmicin pharmacokinetic parameters and individualizing therapy.