Population analysis of once-daily dosing of gentamicin in patients with neutropenia

Background: Aminoglycoside antibiotics are used as first-line therapy in the treatment of patients with febrile neutropenia. However, there is little information on the pharmacokinetics of aminoglycosides in this specific patient group and whether they differ from the accepted population values. Aim: To determine the population pharmacokinetics of gentamicin for patients with febrile neutropenia, with or without sepsis. Methods: Data were collected from 26 patients with febrile neutropenia receiving once-daily gentamicin. Patient age, height, weight, estimated lean body weight (LBW)), gender, serum creatinine (S-Cr) creatinine clearance (Cl-Cr), and serum drug concentration data were collected. Severity of infection and degree of neutropenia were assessed. An initial mio-stage population analysis using a Bayesian dose-individualisation programme was performed to estimate likely population values of the parameters. If these were significantly different from typical values then a true population analysis was to be performed. Results: Data for 13 female and 13 male patients were collected. Median age was 57 years (range 19 to 87 years), estimated LBW(kg)=66 (+/-10), Cl-Cr, (1/hour)=5.6 (+/-2.0) (mean +/-SD). Results of the two-stage approach follow [initial population values in square brackets] : Cl (1/hour)=0.73 (+/-0.12)x Cl-Cr+0.01xLBW [0.70 (+/- 0.27) x Cl-Cr+0.01xLBW]; Vd (1)=0.28 (+/-0.05)xLBW [0.27 (+/- 0.06)xLBW]. Conclusions: The population values of Cl and Vd from the two-stage approach do not differ significantly from initial population values of Cl and Vd. Patients receiving gentamicin for febrile neutropenia may be considered pharmacokinetically similar to the general population receiving gentamicin.