Probability Assessment Approach to Therapeutic Drug Monitoring: Tobramycin

Pharmacokinetic monitoring is an important therapeutic goal of aminoglycoside therapy. The overall goal of this study was to identify specific patient groups that would derive the maximum benefit from therapeutic drug monitoring services. These groups are patient populations with high probabilities of achieving toxic or subtherapeutic concentrations. Out of a total population of 86 stable, noncritically ill patients, 27 toxic concentrations (trough >2.0 μg/mL) occurred in 15 patients. In comparison to patients (n = 46) with therapeutic concentrations (trough < 2.0 μg/mL, peak >4.0 μg/mL), these patients were older (64 ± 11 vs. 54 ± 18years; p < 0.02) and had a higher percentage of females (66.7 vs. 37 percent; p < 0.05). Those patients with subtherapeutic concentrations (43 concentrations in 25 patients) had higher estimated creatinine clearance values than those with therapeutic concentrations (94 ± 45 vs. 74 ± 27 mL/min; p < 0.005). Probability assessment analysis of the data showed a sevenfold increase in toxic concentrations in patients above 50 years. Females over age 50 had 2.3 times the risk of developing toxic concentrations as males over age 50. In contrast, the development of low concentrations was not predicted by age or sex. Underdosage by ≥30 percent was a reasonable predictor (75 percent) of low peak concentrations. Furthermore, toxic concentrations did not occur in patients who were underdosed, justifying dosage increases prior to obtaining serum concentrations in these patients. The group with the highest probability of attaining therapeutic concentrations was males receiving therapeutic doses who were under age 50 (85.5 percent). Therefore, routine measurement of serum concentrations in this group would have limited cost-benefit potential. It is concluded that a probability assessment approach can be used to facilitate the therapeutic monitoring of tobramycin.