Premium
Effect of glutathione S‐transferase genetic polymorphisms on busulfan pharmacokinetics and veno‐occlusive disease in hematopoietic stem cell transplantation: A meta‐analysis
Author(s) -
Kim Myeong Gyu,
Kwak Arim,
Choi Boyoon,
Ji Eunhee,
Oh Jung Mi,
Kim Kyungim
Publication year - 2019
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.13185
Subject(s) - busulfan , gstp1 , glutathione s transferase , medicine , genotype , hematopoietic stem cell transplantation , pharmacokinetics , oncology , glutathione , gastroenterology , transplantation , pharmacology , biology , genetics , enzyme , biochemistry , gene
Abstract This meta‐analysis was conducted to derive an integrated conclusion about the influence of glutathione S‐transferase (GST) genetic polymorphisms on busulfan pharmacokinetic (PK) parameters and veno‐occlusive disease (VOD). Studies which analysed the effect of GST genetic polymorphisms on area under the curve (AUC), clearance (CL) or VOD were searched for and selected. A pooled analysis was conducted using Comprehensive Meta‐Analysis programme. Nineteen studies were included in this meta‐analysis. GSTA1 *B and GSTM1 null genotypes significantly decreased CL IV of busulfan (standardized difference in means (SDM) = −1.103; P = 0.019 and SDM = −0.418; P = 0.002, respectively). GSTA1 *B significantly increased AUC IV of busulfan (SDM = 0.832; P = 0.046), whereas GSTM1 did not (SDM = 0.155; P = 0.478). The PK parameters of oral busulfan did not differ according to GST genotype. GSTA1, GSTM1 and GSTP1 were not significantly associated with VOD occurrence. GSTA1 and GSTM1 genotypes affected CL IV of busulfan, but only GSTA1 affected AUC IV . There was no significant difference in the PK parameters of oral busulfan (CL PO and AUC PO ) and VOD when only GST genotypes were considered.