Population Pharmacokinetics Of Amikacin In Hematologic Malignant Patients

The patient population comprised 285 hematology patients divided into two groups: one for computing the population model(N= 180) and the other for validation (N= 105). A one-comparment model was used and the following covariates were tested for their influence on clearance (CL) and volume of distribution (VD): age, gender, weigth, parenteral nutrition, creatinine clearance, stage of antineoplasic treatment (induction, consolidation, intensification), time postchemotherapy, clinical diagnosis, ECOG score, neutropenia, hypoalbuminemia, concomitant medication (vancomycin and/or amphotericin B), hyperhidratation and autologous or bone marrow transplant.

The nonlinear mixed-effect model (NONMEM) was used to assess the population pharmacokinetic model of amikacin in this patient population.

The final population model accounting for amikacin pharmacokinetics in hematology patients was : CL= 1.11 Clcr( 1+ 0.17 Acute myelogenous leukemia), Vd= 0.37 TBW ( 1+ 0.30 Hypoalbuminemia) where Clcr and TBW corresponds to the patients´creatinine clearance and total body weight, respectively.This model was subsequently used to predict amikacin serum levels obtained in the validation population by ” a priori ” and Bayesian methods.