Population Pharmacokinetics of Amikacin in Adult Patients with Cystic Fibrosis [PublishAheadOfPrint]

Practitioners commonly use amikacin in patients with cystic fibrosis. Establishment of the pharmacokinetics of amikacin in adults with cystic fibrosis may increase the efficacy and safety of therapy. This study was aimed to establish the population pharmacokinetics of amikacin in adults with cystic fibrosis. We used serum concentration data obtained during routine therapeutic drug monitoring and explored the influence of patient covariates on drug disposition. We performed a retrospective chart review to collect amikacin dosing regimens, serum amikacin concentrations, blood sampling times, and patient's characteristics from adults with cystic fibrosis admitted for treatment of acute pulmonary exacerbations. Amikacin concentrations were retrospectively collected for 49 adults with cystic fibrosis, and 192 serum concentrations were available for analysis. A population pharmacokinetic model was developed using non-linear mixed effects modeling with first-order conditional estimation method. A two-compartment model with first-order elimination best-described amikacin pharmacokinetics. Creatinine clearance and weight were identified as significant covariates for CL and Vd, respectively, in the final model. Residual variability was modeled using a proportional error model. Typical estimates for clearance, central and peripheral volume, and inter-compartmental clearance were 3.06 L/h, 14.4 L, 17.1 L and 0.925 L/h, respectively. The pharmacokinetics of amikacin in individuals with cystic fibrosis seems to differ compared with individuals without cystic fibrosis. However, further investigations are needed to confirm these results, and thus the need for variations in amikacin dosing. Future pharmacodynamic studies will potentially establish optimal amikacin dosing regimens for the treatment of acute pulmonary exacerbations in adult patients with CF.

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