Factors affecting gentamicin pharmacokinetics in septic patients

Background: This prospective, comparative study was designed to estimate the volume of distribution (V(d)) and elimination rate constant (K(e)) of gentamicin and to determine the clinical factors affecting the pharmacokinetics of gentamicin in different stages of sepsis. Method: Seventy-seven critically ill patients treated with gentamicin for gram- negative sepsis were included. These septic patients were divided into hyperdynamic septic and hypodynamic septic groups according to cardiac index. Twenty-seven patients who received postoperative prophylactic gentamicin were recruited as controls. Results: Fifty-two patients in the hyperdynamic septic group had a significantly larger V(d) than those in the hypodynamic septic and control groups. The V(d) was correlated significantly with both Acute Physiological Score (APS) (r=0.340, P<0.01) and cardiac index (r=0.394, P<0.01). The K(e) of gentamicin correlated significantly with both blood urea nitrogen (BUN) (r=0.565, P<0.01) and serum creatinine level (r=0.563, P<0.01). Conclusion: The increased V(d) in the septic patients was related to the severity of illness and magnitude of cardiac output. The K(e) of gentamicin was correlated with the serum creatinine level.