Altered aminoglycoside pharmacokinetics in the critically ill

We studied prospectively 49 patients being treated in an intensive care unit with aminoglycosides for gram-negative sepsis. Pharmacokinetic data were calculated from three post-dose serum levels using a one-compartment model. Doses required to achieve peak levels between 5 and 10 mg/l with trough levels approximately 1.0 mg/l ranged between 2 and 12 mg/kg per day (mean dose 7 mg/kg per day). During therapy 60% of the patients had a change in their apparent volume of distribution (Vd) of greater than 20%. These patients were likely to have confirmed infection and to be febrile at the start of treatment. Two to three weeks after discharge ten patients were restudied after a single dose of aminoglycoside. There was a reduction in mean Vd from 0.24 to 0.18 l/kg (P less than 0.02). Critically ill patients have significantly larger volumes of distribution and may require larger doses per kilogram of body weight of aminoglycoside to achieve therapeutic concentrations. Due to considerable variation in kinetic parameters, the use of standard doses or dosing nomograms is not recommended.