Asparaginase may influence dexamethasone pharmacokinetics in acute lymphoblastic leukemia

Abstract

Purpose: Dexamethasone is used widely in oncology, but pharmacokinetic studies are lacking. We evaluated dexamethasone pharmacokinetics in children with acute lymphoblastic leukemia. Patients and Methods: We assessed 214 children with acute lymphoblastic leukemia who received 418 courses of oral dexamethasone (8 mg/m2/d) on days 1 and 8 of reinduction. Extensive asparaginase use preceded reinduction in the 101 children in the standard/high-risk treatment arm but not in the 113 children in the low-risk treatment arm. A one-compartment model with first-order absorption and disposition was fit to dexamethasone plasma concentrations by using maximum a posteriori probability estimation; we evaluated covariates by using linear mixed models. Results: Interpatient and intrapatient variabilities in apparent clearance were substantial; they were 46% and 53%, respectively. Variability was explained by the serum albumin concentration (P < .0001), concomitant use of fentanyl (P = .008) and ketoconazole (P = .03), and age (P = .006). Apparent clearance was higher in the low-risk arm (P < .001) and was related to a greater serum albumin concentration (P