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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
Author(s) -
Chrzanowska Maria,
Sobiak Joanna,
Grund Grzegorz,
Wachowiak Jacek
Publication year - 2011
Publication title -
pediatric transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 69
eISSN - 1399-3046
pISSN - 1397-3142
DOI - 10.1111/j.1399-3046.2010.01418.x
Subject(s) - medicine , etoposide , total body irradiation , pharmacokinetics , transplantation , hematopoietic stem cell transplantation , acute lymphocytic leukemia , conditioning , conditioning regimen , gastroenterology , haematopoiesis , regimen , urology , leukemia , chemotherapy , lymphoblastic leukemia , stem cell , pharmacology , cyclophosphamide , biology , genetics , statistics , mathematics
Chrzanowska M, Sobiak J, Grund G, Wachowiak J. 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.
Pediatr Transplantation 2011: 15:96–102. © 2010 John Wiley & Sons A/S. 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.