Population pharmacokinetics of gentamicin in acute lymphoblastic leukemia pediatric patients compared to non-oncology patients

Abstract

Understanding the pharmacokinetics of gentamicin is essential in special populations, such as pediatric patients with acute lymphoblastic leukemia (ALL), in light of previous studies indicating that ALL patients have a lower volume of distribution than non-ALL patients. Furthermore, validation of such results is needed to ensure their clinical application. Accordingly, this single-center, retrospective, cross-sectional study compares the pharmacokinetic parameters of volume of distribution and clearance (Cl) of gentamicin between ALL and non-ALL patients. Inclusion criteria were pediatric patients aged between 1 and 14 years with or without ALL and receiving intravenous gentamicin for treatment courses > 72 h. Patients' characteristics, such as age, sex, height, serum albumin, diagnosis, serum creatinine (Scr) concentration, dosing, and pharmacokinetic information, including peak and trough concentrations, were retrieved. The study scrutinized a total of 115 pediatric patients, comprising toddlers (15.7 %), children (76.5 %), and adolescents (7.8 %). All patients received gentamicin every 8 h, with an average dose of 2.50 (0.64) mg/kg. Patients were divided into two groups based on disease state, with 45.2 % (n = 52) in the non-ALL group and 54.8 % (n = 63) in the ALL group. Both groups had similar characteristics in terms of gender, weight, body surface area, and dose. The only significant covariates identified were weight and creatinine clearance (Cl_cr) for volume of distribution (V_d). A significant difference was found in Scr, Cl_cr, and blood urea nitrogen (BUN); however, no significant difference between ALL and non-ALL patients emerged in the volume of distribution or Cl. In conclusion, the study findings indicate that dosing requirements were similar between the two groups. Further prospective studies with larger sample sizes are warranted.

Keywords: Acute Lymphoblastic Leukemia (ALL); Gentamicin; Pediatric; Pharmacokinetics (PK); Therapeutic Drug Monitoring (TDM).

Fig. 1

Diagnostic plot for observed concentrations vs. predicted concentrations: population predictions (left) and individual predictions (right).

Fig. 2

Population weighted residuals (left), individual weighed residuals plot (middle), and normalized prediction distribution error plot (right).

Fig. 3

Visual predictive check plot. The solid lines represent the 10th, 50th, and 90th percentiles of observed data. The shaded regions represent the 90% confidence interval around the 10th, 50th, and 90th percentiles of simulated data. The circles are observed concentrations.