Pharmacokinetics of once-daily dosing of gentamicin in surgical intensive care unit patients with open fractures

OBJECTIVE: To compare the first-dose pharmacokinetic parameters of gentamicin 6 mg/kg and 2 mg/kg in stable, nonobese surgical intensive care unit patients with open extremity fractures receiving gentamicin prophylactically. METHODS: Serial blood samples were obtained over 8 or 24 hours following the first dose of gentamicin. Serum concentrations of gentamicin were measured using fluorescence polarization immunoassay and analyzed by noncompartmental means. RESULTS: Eleven patients were enrolled, 7 in the 6 mg/kg group and 4 in the 2 mg/kg group. The median (6 vs. 2 mg/kg) age was 29 versus 28 years; serum creatinine 80 versus 88 mumol/L; and APACHE II score 13 versus 10. The mean +/- SD (micrograms/mL) of concentration at the end of the 30-minute infusion (Cmax), concentration 30 minutes after the end of the infusion (Cpk), and concentration at the end of the dosing interval for 6 versus 2 mg/kg were: 35.0 +/- 19.0 versus 10.1 +/- 1.77; 17.0 +/- 2.7 versus 5.4 +/- 0.4, and 0.45 +/- 0.31 versus 0.69 +/- 0.11, respectively. Area under the curve0-infinity (AUC0-infinity), apparent volume of distribution, and half-life were: 89.0 +/- 28.9 versus 26.1 +/- 1.2 mg.h/L, 0.40 +/- 0.10 versus 0.47 +/- 0.14 L/kg, and 4.0 +/- 1.1 versus 4.3 +/- 1.5 h, respectively. CONCLUSIONS: The first-dose pharmacokinetics of gentamicin 6 mg/kg resulted in a proportional rise in Cmax, Cpk, and AUC0-infinity compared with gentamicin 2 mg/kg in patients with open fractures, but with greater variability.