Five clinical strategies for monitoring serum tobramycin concentrations were compared in a population of children and young adults with normal renal function receiving tobramycin for suspected sepsis. The drug monitoring strategies were evaluated on the basis of the ability of each to predict subsequent drug levels. The strategies included 3 methods requiring assessment of individual drug disposition: (a) measurement of peak drug concentrations after 2 separate doses; (b) a 3-point kinetic study to define distribution volume and elimination rate; (c) a 3-point kinetic study with adjustment of the value for elimination rate to account for deep compartment drug accumulation; and 2 strategies using a fixed-dose approach in which prediction of individual levels was made on the basis of mean population kinetic parameters. Although all methods were of similar accuracy, the fixed-dose strategy was the most precise in predicting subsequent serum tobramycin levels (95% tolerance limits = 84–135% of predicted). Poor performance of the other strategies was accounted for by interpatient variability of tobramycin disposition that was small relative to the intrapatient variability in these measurements. We conclude that these strategies for aminoglycoside serum level monitoring, which have proven beneficial in patients with impaired renal function, afford little benefit to children and young adults with normal renal function. Administration of these drugs on a fixed-dose schedule without serum concentration monitoring appears to be warranted in this select population. Alternatively, specific strategies for this population must be developed that consider the small interindividual differences in drug disposition and low incidence of toxicity.
ASJC Scopus subject areas
- Pharmacology (medical)