Pharmacokinetics of Once-Dally Dosing of Gentamicin in Surgical Intensive Care Unitpatients with Openfractures

Abstract

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 μmol/L; and APACHE H score 13 versus 10. The mean ± SD (μg/mL) of concentration at the end of the 30-minute infusion (C_max), concentration 30 minutes after the end of the infusion (C_pk), 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 curves_0-∞ (AUC_0-∞), 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 C_max, C_pk, and AUC_0-∞, compared with gentamicin 2 mg/kg in patients with open fractures, but with greater variability.