Related Experiment Video
Updated: May 26, 2026

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
Population pharmacokinetics of cyclophosphamide in patients with thalassemia major undergoing HSCT
P Balasubramanian1, S Desire, J C Panetta
1Department of Haematology, Christian Medical College, Vellore, India. bpoonkuzhali@cmcvellore.ac.in
Abstract:
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<0.002) and thus the area under the concentration curve (P<0.05) of CY. This covariate model may be used to design and plan targeted dose therapy in this group of pediatric patients, if clinical outcome association with CY PK are proved and target range established.
Related Concept Videos
Pharmacokinetics in Pediatric Patients: Drug Excretion
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
Drug Accumulation During Multiple Dosing: Intermittent IV Infusions
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Pharmacokinetics in Pediatric Patients: Drug Metabolism
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
