Variability in aminoglycoside pharmacokinetics in critically ill surgical patients

The pharmacokinetics of the aminoglycosides were evaluated in 181 patients admitted to a surgical ICU. Pharmacokinetic parameters changed from 16% to 40% during therapy requiring multiple dosage adjustments and nearly nine drug levels per patient. Dosage adjustments resulted in peak and trough serum concentrations within the therapeutic range 71% and 74% of the time. Aminoglycoside half-life (T1/2) ranged from 1.1 to 69.3 h. Aminoglycoside volume of distribution also varied considerably with an average value of 0.36 L/kg. During therapy most patients gained weight (average 8.4 kg) which correlated with their corresponding fluid gain of 11.6 L. Pharmacokinetic parameters were variable even in patients with a normal serum creatinine. Less than 50% of these patients received the recommended daily dosages. This study suggests that the aminoglycoside volume of distribution in critically ill surgical patients differs from general hospital patients and pharmacokinetic parameters change considerably during therapy. We recommend obtaining timed serum aminoglycoside concentrations early in therapy and adjusting drug dosages as needed to maintain serum concentrations in the therapeutic range.