Population pharmacokinetics of amikacin in patients with haematological malignancies

The aim of this study was to analyse the pharmacokinetic behaviour of amika cin in patients with haematological malignancies using a mixed-effect model and sparse data collected during routine clinical care. The patient popula tion comprised 207 haematology patients divided into two groups: one for co mputing the population model (n = 134) and the other for validation (n = 73 ), A one-compartment model was used and the following covariates were teste d for their influence on clearance and volume of distribution: age, gender, weight, parenteral nutrition, creatinine clearance, stage of antineoplasti c treatment (induction, consolidation, intensification), number of weeks po stchemotherapy, clinical diagnosis, Eastern Cooperative Oncology Group scor e, neutropenia, hypoalbuminaemia, concomitant medication (vancomycin and/or amphotericin B), overhydration, and autologous or allogenic bone marrow tr ansplant. 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 hypoalbumin aemia proved to be the most important covariates explaining the interindivi dual variability in amikacin pharmacokinetics in patients with haematologic al malignancies. The predictive performance of this population model for am ikacin serum concentrations seems suitable for clinical purposes.