Influence of glutathioneS-transferase A1, P1, M1, T1 polymorphisms on oral busulfan pharmacokinetics in children with congenital hemoglobinopathies undergoing hematopoietic stem cell transplantation
| Autor: | Eli Sprecher, Jacob M. Rowe, Edna Efrati, Hela Elkin, Ronit Elhasid, Lior Adler, Norberto Krivoy |
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| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
business.industry medicine.medical_treatment Cmax Hematology Hematopoietic stem cell transplantation medicine.disease Gastroenterology GSTP1 Graft-versus-host disease Oncology Pharmacokinetics Internal medicine Pediatrics Perinatology and Child Health Genotype Immunology Toxicity medicine business Busulfan medicine.drug |
| Zdroj: | Pediatric Blood & Cancer. 55:1172-1179 |
| ISSN: | 1545-5009 |
| DOI: | 10.1002/pbc.22739 |
| Popis: | Background Busulfan (BU), often used in high dose for myeloablation before hematopoietic stem cell transplantation (HSCT), has been implicated in certain HSCT toxicities, including the occurrence of hepatic veno-occlusive disease (HVOD). In addition to weight and age, gene polymorphisms in specific members of the glutathione-transferase (GST) gene family (A1, P1, M1, and T1), involved in BU metabolism, may play a role in the wide inter-patient variability in systemic BU concentrations. Procedure The present study integrated clinical data regarding the occurrence of HVOD, graft versus host disease (GVHD), BU pharmacokinetics and GSTA1, GSTP1, GSTM1, and GSTT1 genotypes of 18 children who received BU in their pre-HSCT conditioning regimen. The children were all treated for congenital hemoglobinopathies and were all of Arab Moslem descent. Results The data demonstrate an association between GSTA1 and GSTP1 genotypes and BU-maximal concentration (Cmax) (P = 0.01, P = 0.02, respectively), area under the concentration-time curve (AUC) (P = 0.02, P = 0.01, respectively) and oral BU clearance/kg body weight (P |
| Databáze: | OpenAIRE |
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