title: Pharmacokinetics of high-dose etoposide administered in combination with fractionated total-body irradiation as conditioning for allogeneic hematopoietic stem cell transplantation in children with acute lymphoblastic leukemia.
abstract: Etoposide (VP-16) is one of the most widely used antitumor agents in pediatric oncology as well as chemotherapeutic agents used in conditioning regimen prior to allo-HSCT for childhood ALL. This study included 21 children with ALL who underwent allo-HSCT after conditioning with FTBI and high-dose of VP-16 (60 mg/kg) given intravenously as single four-h infusion on day -3 (n=2) or day -4 (n=19) prior to allo-HSCT. Blood samples were collected at defined time intervals until 120 h elapsed from the end of infusion. VP-16 plasma concentrations were determined using validated HPLC method. Three-compartment model was assumed for assessing PK parameters of VP-16. The median value of VP-16 C(max) measured at the end of infusion was 188.0 μg/mL (range 148.0-407.0 μg/mL). Out of 21 studied children, VP-16 was still detectable in 17 patients 72 h (median concentration 0.31 μg/mL) and in eight patients 96 h (median concentration 0.31 μg/mL) after the end of infusion. VP-16 concentration 96 h after the end of infusion was positively correlated with VP-16 AUC and negatively correlated with VP-16 CL normalized to body weight.
authors.affiliation: Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poznań, Poland. mchrzan@ump.edu.pl
authors.forename: Maria
authors.initials: M
authors.lastname: Chrzanowska
authors.forename: Joanna
authors.initials: J
authors.lastname: Sobiak
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Grund
authors.forename: Jacek
authors.initials: J
authors.lastname: Wachowiak
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003131:Combined Modality Therapy / Q000379:methods*; D005047:Etoposide / Q000493:pharmacokinetics*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods*; D014916:Whole-Body Irradiation
chemical_list: D000970:Antineoplastic Agents; D005047:Etoposide