Pharmacokinetics of gentamicin in critically ill patients: pilot study evaluating the first dose

Gentamicin is extensively used in the treatment of severe Gram-negative bacterial infections. A loading dose of 7 mg/kg is recommended to achieve a maximum concentration (C(max)) above 16 mg/L. We studied gentamicin pharmacokinetic data from patients treated between January 2006 and June 2008 in two intensive-care units. The Sawchuk and Zaske one-compartment pharmacokinetic model was used to estimate the gentamicin volume of distribution (the 32 patients had a median age of 68 years (23 men)). The median volume of distibution (V(d)) per kilogram of body weight (V(d)/kg) was 0.41 L/kg (interquartile range of 0.36-0.46 L/kg), with no correlations with age, Charlson comorbidity score, sequential organ failure assessment (SOFA) score and creatinine serum level (r(2) = 0.016, 0.058, 0.037, and 0.067, respectively). Women had a significantly higher median V(d)/kg (0.50 vs. 0.40 L/kg, p 0.002) and lower C(max) (15.2 vs. 18.5 mg/L, p 0.016), despite similar dose/kg. In a logistic regression model, only sex (female: OR 0.032; 95% CI 0.03-0.387) and dose/kg (per mg/kg: OR 3.21; 95% CI 1.17-8.79) were significantly associated with the achievement of C(max) above 16 mg/L. Gentamicin clearance was 57 mL/min (interquartile range of 44.7-78 mL/min) and decreased with age (r(2) = 0.178, p 0.016), SOFA score (r(2) = 0.199, p 0.011) and creatinine clearance (r(2) = 0.258, p 0.003). Gentamicin V(d) was increased in critically ill patients, particularly in women. Therefore, high gentamicin loading doses should be given to all patients, especially women, independently of organ failure. Gentamicin clearance decreases with age, SOFA score, and renal failure.