Population pharmacokinetics of amikacin in patients with haematological malignancies.

Abstract

The aim of this study was to analyse the pharmacokinetic behaviour of amikacin in patients with haematological malignancies using a mixed-effect model and sparse data collected during routine clinical care. The patient population comprised 207 haematology patients divided into two groups: one for computing the population model (n = 134) and the other for validation (n = 73). A one-compartment model was used and the following covariates were tested for their influence on clearance and volume of distribution: age, gender, weight, parenteral nutrition, creatinine clearance, stage of antineoplastic treatment (induction, consolidation, intensification), number of weeks postchemotherapy, clinical diagnosis, Eastern Cooperative Oncology Group score, neutropenia, hypoalbuminaemia, concomitant medication (vancomycin and/or amphotericin B), overhydration, and autologous or allogenic bone marrow transplant. The nonlinear mixed-effect model (NONMEM) was used to assess the population pharmacokinetic model of amikacin in these patients. Apart from bodyweight and renal function, acute myeloblastic leukaemia and hypoalbuminaemia proved to be the most important covariates explaining the interindividual variability in amikacin pharmacokinetics in patients with haematological malignancies. The predictive performance of this population model for amikacin serum concentrations seems suitable for clinical purposes.