Population Pharmacokinetic Analysis of Decitabine in Pediatric Patients With Acute Myeloid Leukemia

Dacogen, the formulated product of the pharmaceutically active agent decitabine (5 aza-2'-deoxycytidine), is approved for treatment of myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML). The current analysis was performed to characterize the pharmacokinetics of decitabine in pediatric patients with AML and evaluate their consistency with the PK in adult patients. A population pharmacokinetic model was developed by pooling decitabine concentration-time data from 5 adult (AML and MDS) and 2 pediatric (AML) studies. A total of 840 concentration-time data points obtained from 71 adults and 28 pediatric subjects (1 to 16 years old) were available for analysis. A 2-compartment linear pharmacokinetic (PK) model with allometric scaling using body surface area accounting for body size adequately described the PK of decitabine. After accounting for body size, decitabine pharmacokinetics were not affected by age, sex, race, dosing regimen, renal function (creatinine clearance), bilirubin, or disease type (AML or MDS) and all PK parameters (including clearance, steady-state volume of distribution, maximum concentration, time to reach maximal concentration, and terminal half-life) were comparable between adult and pediatric patients. Simulated concentration-time profiles using the final population PK model suggested that decitabine exposure at steady state was similar in adults and pediatrics for a 20 mg/m² decitabine dose administered as a 1-hour infusion once daily. The current analysis suggests that decitabine PK is similar in pediatric AML patients and a combined adult AML and MDS population.