Area under the curve achievement of once daily tobramycin in children with cystic fibrosis during clinical care

Background The area under the concentration-time curve over 24 hours (AUC(24)) is frequently utilized to monitor tobramycin exposure in children with cystic fibrosis (CF). An understanding of exposure target achievement during clinical implementation of an AUC(24)based approach in children is limited. Methods A retrospective chart review was performed in children with CF treated with once daily tobramycin and drug concentration monitoring at a pediatric CF center. During clinical care AUC(24)was estimated using a traditional log-linear regression approach (LLR). AUC(24)was also estimated retrospectively using a pharmacokinetic model-based Bayesian forecasting approach (BF). AUC(24)achievement after both approaches were compared. Results In 77 treatment courses (mean age, 12.7 +/- 5.0 years), a target AUC(24)100 to 125 mg h/L was achieved after starting dose in 21 (27%) and after initial dose adjustment in 35 (45%). In the first 7 days of treatment, 24 (32%) required >= 3 dose adjustments, and the mean number of drug concentrations measured was 7.1 +/- 3.2. Examination of a BF approach demonstrated adequate prediction of measured tobramycin concentrations (median bias -2.1% [95% CI -3.1 to -1.4]; median precision 7.6% [95% CI, 7.1%-8.2%]). AUC(24)estimates utilizing the BF approach were higher than the LLR approach with a mean difference of 6.4 mg h/L (95% CI, 4.8 to 8.0 mg h/L). Conclusions Achievement of a narrow AUC(24)target is challenging during clinical care, and dose individualization is needed in most children with CF. Implementing a BF approach for estimating AUC(24)in children with CF is supported.