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

Hisham S Abou-Auda; Fatimah Alotaibi; Sary Alsanea; Abdulrahman Alwhaibi; Mohammed M Almutairi; Ziyad Alrabiah; Abdullah Alsultan; Majed Al Jeraisy

doi:10.1016/j.jsps.2024.102060

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

Saudi Pharm J. 2024 May;32(5):102060. doi: 10.1016/j.jsps.2024.102060. Epub 2024 Apr 1.

Authors

Hisham S Abou-Auda¹, Fatimah Alotaibi^{1

2}, Sary Alsanea³, Abdulrahman Alwhaibi¹, Mohammed M Almutairi³, Ziyad Alrabiah¹, Abdullah Alsultan¹, Majed Al Jeraisy^{2

4

5}

Affiliations

¹ Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
² King Abdullah Specialist Children's Hospital, Ministry of National Guard, Saudi Arabia.
³ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
⁴ King Abdullah International Medical Research Center, Saudi Arabia.
⁵ King Saud Bin Abdulaziz University for Health Sciences, Saudi Arabia.

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).