Population pharmacokinetics of cyclophosphamide in patients with thalassemia major undergoing HSCT

CY in combination with BU is a widely used conditioning regimen for haematopoietic SCT (HSCT). The aim of this study was to evaluate the pharmacokinetics (PK) of CY and its major metabolite 4-hydroxyCY (HCY) in patients with thalassemia undergoing HSCT. A total of 55 patients received BU (16 mg/kg) followed by CY (160–200 mg/kg) both over 4 days before HSCT. A population PK model was developed to describe the disposition of CY and HCY and the inter-individual (IIV) and inter-occasion variability (IOV). The model was also used to determine the effects covariates including: demographics, Lucarelli classification and polymorphisms in enzymes involved in the metabolism or biotransformation of CY had on CY and HCY disposition. Overall, 17–114% IIV and 12–103% IOV in CY and HCY PK parameters were observed. Body weight and age were the main covariates, which explained the largest portion of the IIV. In addition, CYP2C9 * 2 explained a significant portion of the IIV in the clearance ( P