Comparison of the predictive utility of two methods of dosing tobramycin in cystic fibrosis patients

Aminoglycosides are often used to treat severe gram-negative infections. It is desirable to achieve adequate peak concentrations for successful eradication of the infection, while minimizing the trough concentration, in order to decrease the amount of drug presented to the renal proximal tubule and thus theorectically decrease the risk of nephrotoxicity. For these reasons, serum aminoglycoside concentrations are monitored. Cystic fibrosis (CF) patients are frequently hospitalized for treatment of pseudomonal pulmonary infections. CF patients have been shown to have altered pharmacokinetic characteristics in handling genamicin, tobramycin, and amikacin. More specifically, they generally have an increased volume of distribution (Vd) and an increased total body clearance. The mechanism responsible for these altered pharmacokinetic characteristics is not clear. The primary objective of this study was to determine whether there was a difference in the predictive utility of the two methods in CF patient. A secondary objective was to determine if either method more frequently resulted in predicted or actual trough serum tobramycin concentrations of greater than 2.0 mg/l.